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Two cases of sporadic CJD with clotting disorders have been identified, but this may represent a chance event., Sporadic Creutzfeldt-Jakob disease (sCJD) has not been previously reported in patients with clotting disorders treated with fractionated plasma products. We report 2 cases of sCJD identified in the United Kingdom in patients with a history of extended treatment for clotting disorders; 1 patient had hemophilia B and the other von Willebrand disease. Both patients had been informed previously that they were at increased risk for variant CJD because of past treatment with fractionated plasma products sourced in the United Kingdom. However, both cases had clinical and investigative features suggestive of sCJD. This diagnosis was confirmed in both cases on neuropathologic and biochemical analysis of the brain. A causal link between the treatment with plasma products and the development of sCJD has not been established, and the occurrence of these cases may simply reflect a chance event in the context of systematic surveillance for CJD in large populations.

IntroductionCreutzfeldt-Jakob disease (CJD) is a human prion disease that occurs in sporadic, genetic and acquired forms. Variant CJD (vCJD) is an acquired form first identified in 1996 in the UK. To date, 178 cases of vCJD have been reported in the UK, most of which have been associated with dietary exposure to the bovine spongiform encephalopathy agent. Most vCJD cases have a young age of onset, with a median age at death of 28 years. In the UK, suspected cases of vCJD are reported to the UK National Creutzfeldt-Jakob Disease Research & Surveillance Unit (NCJDRSU). There is, however, a concern that the national surveillance system might be missing some cases of vCJD or other forms of human prion disease, particularly in the older population, perhaps because of atypical clinical presentation. This study aims to establish whether there is unrecognised prion disease in people aged 65 years and above in the Scottish population by screening banked brain tissue donated to the Edinburgh Brain Bank (EBB).MethodsNeuropathological screening of prospective and retrospective brain tissue samples is performed. This involves histopathological and immunohistochemical analysis and prion protein biochemical analysis. During the study, descriptive statistics are used to describe the study population, including the demographics and clinical, pathological and referral characteristics. Controlling for confounders, univariate and multivariate analyses will be used to compare select characteristics of newly identified suspect cases with previously confirmed cases referred to the NCJDRSU.Ethics and disseminationBrain tissue donations to EBB are made voluntarily by the relatives of patients, with consent for use in research. The EBB has ethical approval to provide tissue samples to research projects (REC reference 16/ES/0084). The findings of this study will be disseminated in meetings, conferences, workshops and as peer-reviewed publications.Trial registration numbers10/S1402/69 and 10/S1402/70

Objective The study aims to assess whether unintended children experience slower growth than intended children. Methods We analysed longitudinal data linked to the Karonga Health and Demographic Surveillance Site collected over three rounds between 2008 and 2011 on women’s fertility intentions and anthropometric data of children. Using the prospective information on fertility intention we assessed whether unintended children are more likely to be stunted than intended children. We applied Propensity Score Matching technique to control for endogenous factors affecting both the probability that a family has an unwanted birth and a child with poor health outcomes. Results We found that 24 % of children from unwanted pregnancies were stunted compared with 18 % of mistimed pregnancies and 17 % of those from wanted pregnancies. However, these differences in probability of children being stunted, though in the expected direction, were not significant either for large or small families, after controlling for age. The number of children in the household was associated with stunting and boys were substantially more likely to be stunted than girls. Conclusion We found no significance difference in probability of being stunted by mother’s fertility intention.

OBJECTIVE: To compare socio-demographic patterns in access to antiretroviral therapy (ART) across four community HIV cohort studies in Africa. METHODS: Data on voluntary counselling and testing and ART use among HIV-infected persons were analysed from Karonga (Malawi), Kisesa (Tanzania), Masaka (Uganda) and Manicaland (Zimbabwe), where free ART provision started between 2004 and 2007. ART coverage was compared across sites by calculating the proportion on ART among those estimated to need treatment, by age, sex and educational attainment. Logistic regression was used to identify socio-demographic characteristics associated with undergoing eligibility screening at an ART clinic within 2 years of being diagnosed with HIV, for three sites with information on diagnosis and screening dates. RESULTS: Among adults known to be HIV-infected from serological surveys, the proportion who knew their HIV status was 93% in Karonga, 37% in Kisesa, 46% in Masaka and 25% in Manicaland. Estimated ART coverage was highest in Masaka (68%) and lowest in Kisesa (2%). The proportion of HIV-diagnosed persons who were screened for ART eligibility within 2 years of diagnosis ranged from 14% in Kisesa to 84% in Masaka, with the probability of screening uptake increasing with age at diagnosis in all sites. CONCLUSIONS: Higher HIV testing rates among HIV-infected persons in the community do not necessarily correspond with higher uptake of ART, nor more equitable treatment coverage among those in need of treatment. In all sites, young adults tend to be disadvantaged in terms of accessing and initiating ART, even after accounting for their less urgent need.

OBJECTIVES: Developing countries are undergoing demographic transition with a shift from high mortality caused by communicable diseases (CD) to lower mortality rates caused by non-communicable diseases (NCD). HIV/AIDS has disrupted this trend in sub-Saharan Africa. However in recent years HIV-associated mortality has been reduced with the introduction of widely available antiretroviral therapy (ART). Side effects of ART may lead to increased risk of cardiovascular diseases raising the prospects of an accelerated transition towards NCD as the primary cause of death. We report population-based data to investigate changes in cause of death owing to NCD during the first 4 years after introduction of HIV treatment. METHODS: We analysed data from a demographic surveillance system in Karonga district Malawi from September 2004 to August 2009. ART was introduced in mid-2005. Clinician review of verbal autopsies conducted 2-6 weeks after a death was used to establish a single principal cause of death. RESULTS: Over the entire period there were 905 deaths AIDS death rate fell from 505 to 160/100000 person-years and there was no evidence of an increase in NCD rates. The proportion of total deaths attributable to AIDS fell from 42% to 17% and from NCD increased from 37% to 49%. DISCUSSION: Our findings show that 4 years after the introduction of ART into HIV care in Karonga district all-cause mortality has fallen dramatically with no evidence of an increase in deaths owing to NCD. (c) 2012 Blackwell Publishing Ltd.

The Karonga Health and Demographic Surveillance System ( Karonga HDSS) in northern Malawi currently has a population of more than 35 000 individuals under continuous demographic surveillance since completion of a baseline census (2002-2004). The surveillance system collects data on vital events and migration for individuals and for households. It also provides data on cause-specific mortality obtained by verbal autopsy for all age groups, and estimates rates of disease for specific presentations via linkage to clinical facility data. The Karonga HDSS provides a structure for surveys of socio-economic status, HIV sero-prevalence and incidence, sexual behavior, fertility intentions and a sampling frame for other studies, as well as evaluating the impact of interventions, such as antiretroviral therapy and vaccination programmes. Uniquely, it relies on a network of village informants to report vital events and household moves, and furthermore is linked to an archive of biological samples and data from population surveys and other studies dating back three decades.

Background The risk to public health of onward transmission of variant Creutzfeldt–Jakob disease (vCJD) via blood transfusion and plasma product administration is of on-going concern, particularly with the recent reported detection of abnormal prion protein in a person with haemophilia. Objectives To describe the history of fractionated plasma product exposure in clinical cases of vCJD in the UK. Methods Through examination of records held at the National CJD Surveillance Unit (from relatives, general practices and hospitals). Results Nine out of 168 UK vCJD cases had a history of receipt of fractionated plasma products on 12 different occasions (1 pre-vCJD risk in 1970, the remaining between 1989–1998). According to the UK CJD Incident Panel risk assessment criteria, 11 were low-risk products and one was low or medium risk. Conclusion It is unlikely that any of the UK vCJD clinical cases to date were infected through exposure to fractionated plasma products. However, the possibility that such transmission may result in vCJD cases in the future cannot be excluded.

Background Person-to-person transmission of variant Creutzfeldt-Jakob disease (vCJD) has occurred through blood transfusion and could also theoretically occur as a result of the transplantation of organs or tissues. This study aimed to investigate whether there were transplant-associated vCJD cases in the United Kingdom (UK). Methods Medical histories were reviewed for 177 UK vCJD cases to identify situations where the transplantation of organs or tissues might have occurred. A "look-back" was then performed to trace the respective donors or recipients of the implicated organ or tissue. Results A single patient had undergone an organ (liver) transplant before vCJD onset, from a donor who had died of causes unrelated to vCJD. The look-back was able to trace six other organ or tissue donations made by the same donor. No other situations were identified where the receipt or donation of organs or tissues had occurred in people who went on to develop vCJD. There was considered no need, on this particular occasion, to implement public health measures associated with the organ transplantation, beyond those already in place. Conclusions This study provides no evidence of transplant-associated vCJD in the UK. It is, however, important to continue to seek to identify individuals who might be at risk of vCJD by this route so that appropriate public health measures can be implemented.

SummaryThere is now widespread agreement on the importance of men's role in reproductive decision-making. Several studies have argued that fertility preferences and their translation into behaviour differ between polygamous and monogamous unions. Studies investigating the dominance of men's preferences over women's preferences, in cases of couple disagreement, found mixed evidence of the effect of polygamy. However, an often cited limitation of these studies has been the inability to link husband's intention with each of his wives in a polygamous union. By adding fertility-intention questions to an on-going Demographic Surveillance Site in Karonga District in northern Malawi the fertility preferences and contraceptive use of husbands and wives were investigated. An analysis of the relationship between the level of agreement and disagreement between husbands' and wives' fertility preferences was then performed to gain insight into the reproductive decision-making process of polygamous couples.

OBJECTIVE: To quantify refusal bias due to prior HIV testing, and its effect on HIV prevalence estimates, in general-population surveys. DESIGN: Four annual, cross-sectional, house-to-house HIV serosurveys conducted during 2006-2010 within a demographic surveillance population of 33 000 in northern Malawi. METHODS: The effect of prior knowledge of HIV status on test acceptance in subsequent surveys was analysed. HIV prevalence was then estimated using ten adjustment methods, including age-standardization; multiple imputation of missing data; a conditional probability equations approach incorporating refusal bias; using longitudinal data on previous and subsequent HIV results; including self-reported HIV status; and including linked antiretroviral therapy clinic data. RESULTS: HIV test acceptance was 55-65% in each serosurvey. By 2009/2010 79% of men and 85% of women had tested at least once. Known HIV-positive individuals were more likely to be absent, and refuse interviewing and testing. Using longitudinal data, and adjusting for refusal bias, the best estimate of HIV prevalence was 7% in men and 9% in women in 2008/2009. Estimates using multiple imputations were 4.8 and 6.4%, respectively. Using the conditional probability approach gave good estimates using the refusal risk ratio of HIV-positive to HIV-negative individuals observed in this study, but not when using the only previously published estimate of this ratio, even though this was also from Malawi. CONCLUSION: As the proportion of the population who know their HIV-status increases, survey-based prevalence estimates become increasingly biased. As an adjustment method for cross-sectional data remains elusive, sources of data with high coverage, such as antenatal clinics surveillance, remain important.

In 2009, a pathologist with sporadic Creutzfeldt-Jakob Disease (sCJD) was reported to the Spanish registry. This case prompted a request for information on health-related occupation in sCJD cases from countries participating in the European Creutzfeldt Jakob Disease Surveillance network (EuroCJD). Responses from registries in 21 countries revealed that of 8,321 registered cases, 65 physicians or dentists, two of whom were pathologists, and another 137 healthcare workers had been identified with sCJD. Five countries reported 15 physicians and 68 other health professionals among 2,968 controls or non-cases, suggesting no relative excess of sCJD among healthcare professionals. A literature review revealed: (i) 12 case or small case-series reports of 66 health professionals with sCJD, and (ii) five analytical studies on health-related occupation and sCJD, where statistically significant findings were solely observed for persons working at physicians' offices (odds ratio: 4.6 (95 CI: 1.2-17.6)). We conclude that a wide spectrum of medical specialities and health professions are represented in sCJD cases and that the data analysed do not support any overall increased occupational risk for health professionals. Nevertheless, there may be a specific risk in some professions associated with direct contact with high human-infectivity tissue. Sí

Objective: To assess the performance of rapid HIV antibody tests when used as part of a home-based community wide counseling and testing strategy in northern Malawi.Design: A cross-sectional population survey of HIV infection, 2007 to 2008.Methods: Adults aged 15 years or older in a demographic surveillance area were counseled and then offered an HIV test at their home by government-certified counselors. Two initial rapid tests (Determine and Uni-Gold) were performed on all samples and a third, tie-breaker test (SD Bioline) used to resolve discordant results. All people who wanted to know were posttest-counseled and informed of their results with referral to local clinical services if found to be HIV-positive. Laboratory quality control comprised retesting all positive and every tenth negative venous blood sample collected.Results: A total of 10,819 adults provided venous blood samples for HIV testing, of whom 7.5% (813) were HIV-positive. The accuracy of the parallel testing strategy used was high with 99.6% sensitivity, 100.0% specificity, 99.9% positive predictive value, and 99.9% negative predictive value.Conclusion: Face-to-face rapid testing by health personnel with minimum training at the client's home performs well when used on a wide scale in the community setting.

BackgroundSexual behaviour surveys are widely used, but under-reporting of particular risk behaviours is common, especially by women. Surveys in whole populations provide an unusual opportunity to understand the extent and nature of such under-reporting.MethodsAll consenting individuals aged between 15 and 59 within a demographic surveillance site in northern Malawi were interviewed about their sexual behaviour. Validity of responses was assessed by analysis of probing questions; by comparison of results with in-depth interviews and with Herpes simplex type-2 (HSV-2) seropositivity; by comparing reports to same sex and opposite sex interviewers; and by quantifying the partnerships within the local community reported by men and by women, adjusted for response rates.Results6,796 women and 5,253 men (83% and 72% of those eligible) consented and took part in sexual behaviour interviews. Probing questions and HSV-2 antibody tests in those who denied sexual activity identified under-reporting for both men and women. Reports varied little by sex or age of the interviewer. The number of marital partnerships reported was comparable for men and women, but men reported about 4 times as many non-marital partnerships. The discrepancy in reporting of non-marital partnerships was most marked for married women (men reported about 7 times as many non-marital partnerships with married women as were reported by married women themselves), but was only apparent in younger married women.ConclusionsWe have shown that the under-reporting of non-marital partnerships by women was strongly age-dependent. The extent of under-reporting of sexual activity by young men was surprisingly high. The results emphasise the importance of triangulation, including biomarkers, and the advantages of considering a whole population.

Background:\ud Age at sexual debut is a key behavioural indicator used in HIV behavioural surveillance. Early age at menarche may precipitate early sex through perceived readiness for sex, or through school drop-out, but this is rarely studied. We investigated trends and circumstances of sexual debut in relation to schooling and age at menarche.\ud \ud Methods and Findings:\ud A cross-sectional sexual behaviour survey was conducted on all individuals age 15–59 within a demographic surveillance site in Karonga District, Malawi. Time trends were assessed using birth cohorts. Survival analysis was used to estimate the median age at menarche, sexual debut and first marriage. The 25th centile was used to define “early” sex, and analyses of risk factors for early sex were restricted to those who had reached that age, and were done using logistic regression. Of the 8232 women and 7338 men resident in the area, 88% and 78%, respectively, were seen, and, 94% and 92% of these were interviewed. The median reported age at first sex was 17.5 for women and 18.8 for men. For women, ages at menarche, sexual debut and first marriage did not differ by birth cohort. For men, age at sexual debut and first marriage decreased slightly in later birth cohorts. For both men and women increased schooling was associated with later sexual debut and a longer delay between sexual debut and first marriage, but the associations were stronger for women. Earlier age at menarche was strongly associated with earlier sexual debut and marriage and lower schooling levels. In women early sexual debut (

Context: knowledge of HIV status may influence fertility desires of married men and women. There is little knowledge about the importance of this influence among monogamously married couples and how knowledge of HIV status influences use of contraception among these couples.Methodology: we carried out a cross-sectional analysis of interview data collected between October 2008 and September 2009 on men aged 15–59 years and women aged 15–49 years who formed 1766 monogamously married couples within the Karonga Prevention Study demographic surveillance study in northern Malawi.Results: 5% of men and 4% of women knew that they were HIV positive at the time of interview and 81% of men and 89% of women knew that they were HIV negative. 73% of men and 83% of women who knew that they were HIV positive stated that they did not want more children, compared to 35% of men and 38% of women who knew they were HIV negative. Concordant HIV positive couples were more likely than concordant negative couples to desire to stop child bearing (odds ratio 11.5, 95%CI 4.3–30.7, after adjusting for other factors) but only slightly more likely to use contraceptives (adjusted odds ratio 1.5 (95%CI 0.8–3.3).Conclusion: knowledge of HIV positive status is associated with an increase in the reported desire to cease childbearing but there was limited evidence that this desire led to higher use of contraception. More efforts directed towards assisting HIV positive couples to access and use reproductive health services and limit HIV transmission among couples are recommended

Objective To assess the risk of variant Creutzfeldt-Jakob Disease (vCJD) associated with dental treatment. Design Case-control study, investigation of links between cases. Setting National CJD surveillance, general dental practice and practice boards in Great Britain, 2008-2009. Methods Variant CJD cases were recruited from all those referred between May 1995 and August 2009 (n = 160); controls were recruited from the general population in 2003 using randomly selected geographic clusters and age-weighted sampling of individuals (n = 584). Risk factors were ascertained from dental records, with consent, using a structured questionnaire. Results Dental records were available for fewer cases (49%, 78 out of 160) than control subjects (78%, 457 out of 584). Variant CJD cases were no more or less likely than control subjects to have undergone dental treatment (p ≥0.05). Two cases had attended the same dental practice, but the type and timing of treatments did not provide strong evidence that this was linked to the route of transmission. Conclusion There is no evidence of a vCJD risk associated with dental treatment, but because dental information is limited we cannot exclude this possibility. Improved methods for dental record keeping are recommended to aid future investigations of associations between infectious diseases and dental treatment.