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Descriptions of sporadic Creutzfeldt-Jakob disease (sCJD) in non-White populations are limited. Improved understanding may aid diagnoses and case ascertainment within surveillance programmes. We aimed to: 1) Ascertain the proportion of sCJD cases with non-White ethnicity in the United Kingdom (UK); 2) Compare clinical and investigation findings between non-White and White cases.We analysed records of probable and definite sCJD cases assessed by the UK National CJD Research and Surveillance Unit over 28 years (1990-2017). Cases were stratified into White and non-White groups. Demographics, clinical features, investigation findings, and post-mortem numbers were compared.1697 sCJD cases were included: 1642 (97%) White, 55 (3%) non-White (Asian/Asian British, Black/African/Caribbean). The proportion of non-Whites among sCJD cases is 7% lower than the proportion the non-White population make up in the UK (p 0.001). This was not statistically significant when age-matched by ≥60 years (p = 0.071). Age at symptom onset was 4 years lower in the non-White population (p = 0.007). Clinical and investigation characteristics were otherwise similar between ethnic groupings. The proportion of non-Whites undergoing autopsy and classification as definite was 30% and 24% lower (p 0.001) respectively in comparison to those for White cases.Approximately 3% of sCJD cases in the UK are non-White, despite non-Whites representing approximately 10% of the UK population. This difference was not statistically significant when age-matched at ≥60 years. Non-White cases tend to be younger and likelihood of autopsy is lower; relevant considerations for surveillance programmes. Reasons for these differences in non-White populations are unclear and merit further evaluation.

Human prion diseases comprise a number of rare and fatal neurodegenerative conditions that result from the accumulation in the central nervous system of an abnormal form of a naturally occurring protein, called the prion protein. The diseases occur in genetic, sporadic, and acquired forms: genetic disease is associated with mutations in the prion protein gene (PRNP); sporadic disease is thought to result from a spontaneous protein misfolding event; acquired disease results from transmission of infection from an animal or another human. The potential transmissibility of the prion in any of these forms, either in disease states or during the incubation period, has implications for public health. Here we focus on Creutzfeldt-Jakob Disease (CJD), including variant Creutzfeldt-Jakob Disease (vCJD), although we will also discuss other forms of human prion disease.

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

Human prion diseases, though relatively rare, remain an ongoing public health problem. They are fatal diseases, with unconventional host responses and no early diagnostic tests or robust treatments. Public health measures were put in place to protect the food chain in the United Kingdom from the late 1980s, with similar measures following elsewhere. However, human prion diseases are transmissible through other routes, including through blood transfusion and surgery. As a result, the public health threat remains for all forms of human prion diseases and makes continued surveillance and infection prevention and control imperative.

Look-back studies of blood transfusion in Creutzfeldt-Jakob disease commonly rely on reported history from surrogate witnesses. Data from the UK Transfusion Medicine Epidemiology Review have been analysed to determine the accuracy of the blood donation history provided by the relatives of cases. Our results show that only a small percentage of cases were found to be registered as donors on UK Blood Service (UKBS) databases when there was no family report of blood donation. In contrast, a history of reported donation was less accurate.

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: Recent UNAIDS guidelines recommend measuring concurrency 6 months before the interview date, based on overlapping partnership dates. This has theoretical advantages, but little is known about how well it can be measured in practice. Methods: The assumptions underlying the UNAIDS measure were tested using data from a sexual behaviour survey conducted in rural northern Malawi. All resident adults aged 15-59 were eligible. Questions included self-reported concurrency and dates for all marital and nonmarital partnerships in the past 12 months. Results: A total of 6796 women and 5253 men were interviewed, 83 and 72% of those eligible, respectively. Since few women reported multiple partners, detailed analysis was restricted to men. Overall 19.2% [95% confidence interval (CI) 18.1-20.2] of men self-reported concurrent relationships in the past year (almost all of those with more than one partner). Using overlapping dates the estimate was 16.7% (15.7-17.7). Excluding partnerships which tied on dates (making overlap uncertain) or restricting the analysis to the three most recent partners gave similar results. The UNAIDS 6-month measure was 12.0% (11.1-12.9), and current concurrency was 11.5% (10.6-12.4). The difference between dates-based and self-reported 12-month measures was much larger for unmarried men: 11.1% (9.7-12.4) self-reported; 7.1% (6.9-8.2) on dates. Polygyny (15% of married men) and the longer duration of relationships stabilized the estimates for married men. Nonmarital partnerships were under-reported, particularly those starting longer ago. Conclusions: The difficulties of recall of dates for relationships, and under-reporting of partners lead to underestimation of concurrency using date-based measures. Self-reported concurrency is much easier to measure and appears more complete.

The risk of variant Creutzfeldt-Jakob disease (vCJD) from potentially infected plasma products remains unquantified. This risk has been assessed for 787 UK patients with an inherited bleeding disorder prospectively followed-up for 10-20 years through the UK Haemophilia Centre Doctors' Organisation (UKHCDO) Surveillance Study. These patients had been treated with any of 25 'implicated' clotting factor batches from 1987 to 1999, which included in their manufacture, plasma from eight donors who subsequently developed clinical vCJD. Variant CJD infectivity of these batches was estimated using plasma fraction infectivity estimates and batch-manufacturing data. Total potential vCJD infectivity received by each patient has been estimated by cumulating estimated infectivity from all doses received during their lifetime. Of 787 patients, 604 (77%) were followed-up for over 13 years following exposure to an implicated batch. For these 604 patients, the estimated vCJD risk is ≥ 1% for 595, ≥ 50% for 164 and 100% for 51. This is additional to background UK population risk due to dietary exposure. Of 604 patients, 94 (16%) received implicated batches linked to donors who developed clinical vCJD within 6 months of their donations. One hundred and fifty-one (25%) had received their first dose when under 10 years of age. By 1st January 2009, none of these patients had developed clinical vCJD. The absence of clinical vCJD cases in this cohort to date suggests that either plasma fraction infectivity estimates are overly precautionary, or the incubation period is longer for this cohort than for implicated cellular blood product recipients. Further follow-up of this cohort is needed.

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.

Epidemics of meningococcal meningitis in Africa have plagued the continent for over a century. These epidemics have a strong association with the environment and efforts are being made to develop models to predict both their location and their incidence. This review describes the predictive models based on climate/environmental information currently available, describes work in progress, and presents evidence that the distribution of the epidemics is changing in a pattern that is compatible with changes in the environment. Discussion of priorities for research in the context of the new conjugate vaccines in Africa is also provided.

Surveillance of 75 immunodeficiency patients exposed to UK-sourced immunoglobulin, including batches derived from donors who went on to develop vCJD, has not detected any clinical cases of vCJD, or of asymptomatic infection in 15 patients with available tissue samples of sufficient quality for testing.

OBJECTIVES Meningococcal meningitis is a major public health problem in Africa. This report explores the potential for climate/environmental models to predict the probability of occurrence of meningitis epidemics. METHODS Time series of meningitis cases by month and district were obtained for Burkina Faso, Niger, Mali and Togo (536 district-years). Environmental information (1989-1999) for the continent [soil and land-cover type, aerosol index, vegetation greenness (NDVI), cold cloud duration (CCD) and rainfall] was used to develop models to predict the incidence of meningitis. Meningitis incidence, dust, rainfall, NDVI and CCD were analysed as anomalies (mean minus observed value). The models were developed using univariate and stepwise multi-variate linear regression. RESULTS Anomalies in annual meningitis incidence at district level were related to monthly climate anomalies. Significant relationships were found for both estimates of rainfall and dust in the pre-, post- and epidemic season. While present in all land-cover classes these relationships were strongest in savannah areas. CONCLUSIONS Predicting epidemics of meningitis could be feasible. To fully develop this potential, we require (a) a better understanding of the epidemiological and environmental phenomena underpinning epidemics and how satellite derived climate proxies reflect conditions on the ground and (b) more extensive epidemiological and environmental datasets. Climate forecasting tools capable of predicting climate variables 3-6 months in advance of an epidemic would increase the lead-time available for control strategies. Our increased capacity for data processing; the recent improvements in meningitis surveillance in preparation for the distribution of the impending conjugate vaccines and the development of other early warning systems for epidemic diseases in Africa, favours the creation of these models.

Epidemics of meningococcal meningitis occur in areas with particular environmental characteristics. We present evidence that the relationship between the environment and the location of these epidemics is quantifiable and propose a model based on environmental variables to identify regions at risk for meningitis epidemics. These findings, which have substantial implications for directing surveillance activities and health policy, provide a basis for monitoring the impact of climate variability and environmental change on epidemic occurrence in Africa.

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.

Objective: To investigate the relationship between changing morbidity patterns, the use of hospital services by HlV-infected patients and the uptake of antiretroviral therapy (ART) in England. Design: Prospective serial cross-sectional analyses based on data collected through the National Prospective Monitoring System (NPMS), a multi-centre prospective monitoring system. Setting: HlV-infected patients seen in 10 clinics, five London and five non-London, during the three semesters, 1 January 1996 to 30 June 1997. Main outcome measures: The mean use of hospital services per patient-year, mean new HlV-related opportunistic illnesses per 1000 patient-years and percentage uptake of ART. Results: The use of inpatient services changed particularly among AIDS patients. The mean number of inpatient days for AIDS patients decreased from 19.7 [95% confidence interval (Cl) 13.7-25.7] in 1996 to 11.2 (95% Cl 6.1-15.6) per patient-year in 1997. Concurrently the number of new AIDS-defining events decreased significantly from 567 (95% Cl 529-607) to 203 (95% Cl 183-225) per 1000 patient-years. The overall uptake of ART increased significantly from 33% (95% Cl 31-35%) to 50% (95% CI 48-52%), and a switch from mono or dual to triple therapy or quadruple or more therapy was observed. However, by mid-1997 only 29% (95% Cl 26-32%) of asymptomatic patients and 51% (95% Cl 49-54%) of patients with symptomatic non-AIDS were on ART, compared with 69% (95% Cl 66-71%) of AIDS patients. Conclusion: The observed reduction in new AIDS-defining events has led to a reduction in the need for inpatient hospital care and has been associated with an increased uptake of ART, including a switch to triple therapy. All of these factors are likely to have contributed to the observed reduction in mortality among English AIDS patients. As the overall uptake of ART remained relatively low in English centres further improvements can be anticipated. However, the medium to long-term effects of these treatment regimens will need to be closely monitored.

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.

In this preliminary study we show that in 2008, 3 years after antiretroviral therapy was introduced into the Karonga District, Malawi, a greater than expected number of drug-naive individuals have been infected with HIV-1 subtype C virus harboring major and minor drug resistance mutations (DRMs). From a sample size of 40 reverse transcriptase (RT) consensus sequences from drug-naive individuals we found five showing NRTI and four showing NNRTI mutations with one individual showing both. From 29 protease consensus sequences, again from drug-naive individuals, we found evidence of minor DRMs in three. Additional major and minor DRMs were found in clonal sequences from a number of individuals that were not present in the original consensus sequences. This clearly illustrates the importance of sequencing multiple HIV-1 variants from individuals to fully assess drug resistance.

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 (

By the end of December 2005, a total of 159 cases of variant Creutzfeldt-Jakob disease (vCJD) had been reported in the United Kingdom, of which 153 have so far resulted in death.

Meningitis epidemics have a strong environmental component in Africa with the most severe epidemics occurring in the Sahelian region known as the Meningitis Belt. The objective of this study is to evaluate an ecological model based on absolute humidity and land cover type to predict the location of these epidemics. The risk model is evaluated prospectively based on epidemics occurring in Africa from January 2000 to April 2004. Seventy-one epidemics occurred during this time period affecting 22% of continental African districts. The model predicted their location with a sensitivity of 88%. The evaluation also suggests that epidemics may be extending south of the Sahel, which is consistent with environmental changes in the region. This model could be used to select priority areas for the introduction of the newly developed conjugate meningococcal vaccines. Further studies are needed to enhance our understanding of the complex relationship between meningitis epidemics and the environment.

In 2002, 17 people died from variant CJD (vCJD) in the UK, compared with 20 in 2001 and 28 in 2000. We analysed data for deaths from vCJD since 1995 and estimated the underlying trend in mortality. The trend had a quadratic component (p=0.005), suggesting that the increase was not exponential, and that the previously increasing trend is slowing down. The death rate peaked in 2000. These findings are encouraging, but mortality might increase again in the future.

Mapping an area at risk of epidemics of meningococcal meningitis in Africa has significant implications for their prevention and case treatment, through the targeted development of improved surveillance systems and control policies. Such an area was described using information obtained from published and unpublished reports of meningitis epidemics between 1980 and 1999 and cases of meningococcal disease reported by surveillance systems to WHO. The Sahel bore the greatest epidemic burden, with over two-thirds of documented outbreaks and high attack rates. In addition to those already in the Meningitis Belt, countries affected included Guinea-Bissau, Guinea, Cote d'Ivoire, Togo, the Central African Republic and Eritrea. Elsewhere epidemics were reported from a band of countries around the Rift Valley and Great Lakes regions extending as far south as Mozambique and from here west to Angola and Namibia in southern Africa. The cumulative pan-continental analysis provided evidence of an epidemic-susceptible area which extends beyond the region accepted as the Meningitis Belt and which, moreover, may be partially determined by the physical environment, as shown by a striking correspondence to the 300-1100-mm mean annual rainfall isohyets.

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.

Introduction The potential for vCJD transmission in the healthcare setting has raised concerns over the risk posed by dental surgery. The aim of this study was to determine whether dental treatment was a possible risk factor for vCJD, by looking for links between vCJD cases and whether there was an excess of dental treatment in vCJD cases compared with general population controls. Methods Dental treatment records were collected from general dental practitioners or, where this was not possible, from NHS Dental Practice Board payment schedules. Results Data were available for 49% (79/162) of cases and 82% (503/610) of controls. Two pairs of cases had received dental treatment at the same dental practice, however the type and timing of recorded interventions did not provide strong evidence that this was how vCJD was acquired. The review of specific dental treatments also showed that there was no evidence that vCJD cases experienced an excess of any type of dental treatment compared with controls. Conclusions This study provided no compelling evidence of a strong association between dental treatment and vCJD, however because of the limited availability of dental information, and the possibility of undetected asymptomatic infection, we cannot exclude dental treatment as a possible risk factor for vCJD. We recommend the development of more portable and robust mechanisms for dental record keeping in the UK that are also useable for public health purposes, and support current health policy to ensure that high standards of cleaning and sterilisation of re-usable dental instruments are maintained.

Background Antiretroviral therapy (ART) reduces viral load and has been suggested as a prevention measure to reduce transmission. However there are concerns that this may be counterbalanced to some extent by increased sexual activity associated with improved health and decreased condom use. The impact of ART on rates of HIV-transmission was investigated within HIV discordant couples in rural, Northern Malawi. Methods The study was conducted as part of the Karonga Prevention Study. A demographic surveillance system was started in 2001 and annual home-based HIV sero-surveys added from 2007, with individual counselling and consent. From the first round of the sero-survey, 201 HIV discordant couples (147 male positive, female negative; 54 male negative, female positive) were identified for whom follow-up HIV data were available in the negative partner. Free ART is available at local health facilities and ART use was determined by linkage of data to a clinic based cohort and self-report. Patients attend ART clinics with a guardian who may be the spouse, and are counselled about the need for safer sex. For this analysis participant exposure to ART was defined as having started ART prior to study entry, and follow-up was censored at time of last observation, HIV seroconversion, last negative HIV test, death, departure or dissolution of marriage. Follow-up with re-testing is ongoing. Results So far there are 249 and 99 person-years of follow-up in HIV negative women and men, respectively. 55 of the 201 positive partners had commenced ART at entry and within these couples no HIV transmission occurred over a 3-year follow-up period. Among 146 discordant couples without ART the rate of transmission to females was 5.2 / 100 person years (95% CI 2.7 to 10.5) and to males 1.3/100 person years (95% CI 0.18 to 9.4). Conclusions In HIV discordant couples ART is associated with reduced rates of HIV transmission within partnerships.

I-MOVE-COVID-19 study team: Esther Kissling, Lisa Domegan, Joan O’Donnell, Josephine Murray, Virginia Sandonis Martín, Iván Martínez-Baz, Ausenda Machado, Itziar Casado, Sylvie Behillil, Amparo Larrauri, Ruby Tsang, Marit de Lange, Maximilian Riess, Jesús Castilla, Mark Hamilton, Alessandra Falchi, Francisco Pozo, Linda Dunford, Cristina Burgui, Debbie Sigerson, Thierry Blanchon, Eva María Martínez Ochoa, Jeff Connell, Joanna Ellis, Rianne van Gageldonk-Lafeber, Irina Kislaya, Angela MC Rose, Jamie Lopez Bernal, Nick Andrews, Inmaculada Casas Flecha, Janine Thoulass, Baltazar Nunes, Verónica Gomez, Rita Sa Machado, Vincent Enouf, Pedro Licinio Pinto Leite, Anna Molesworth, Adele McKenna, Janine Thoulass As the COVID-19 pandemic began in early 2020, primary care influenza sentinel surveillance networks within the Influenza - Monitoring Vaccine Effectiveness in Europe (I-MOVE) consortium rapidly adapted to COVID-19 surveillance. This study maps system adaptations and lessons learned about aligning influenza and COVID-19 surveillance following ECDC / WHO/Europe recommendations and preparing for other diseases possibly emerging in the future. Using a qualitative approach, we describe the adaptations of seven sentinel sites in five European Union countries and the United Kingdom during the first pandemic phase (March–September 2020). Adaptations to sentinel systems were substantial (2/7 sites), moderate (2/7) or minor (3/7 sites). Most adaptations encompassed patient referral and sample collection pathways, laboratory testing and data collection. Strengths included established networks of primary care providers, highly qualified testing laboratories and stakeholder commitments. One challenge was the decreasing number of samples due to altered patient pathways. Lessons learned included flexibility establishing new routines and new laboratory testing. To enable simultaneous sentinel surveillance of influenza and COVID-19, experiences of the sentinel sites and testing infrastructure should be considered. The contradicting aims of rapid case finding and contact tracing, which are needed for control during a pandemic and regular surveillance, should be carefully balanced. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101003673. info:eu-repo/semantics/publishedVersion

Introduction In July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe. Aim Using a multicentre test-negative study, we measured COVID-19 vaccine effectiveness (VE) against symptomatic infection. Methods Individuals with COVID-19 or acute respiratory symptoms at primary care/community level in 10 European countries were tested for SARS-CoV-2. We measured complete primary course overall VE by vaccine brand and by time since vaccination. Results Overall VE was 74% (95% CI: 69–79), 76% (95% CI: 71–80), 63% (95% CI: 48–75) and 63% (95% CI: 16–83) among those aged 30–44, 45–59, 60–74 and ≥ 75 years, respectively. VE among those aged 30–59 years was 78% (95% CI: 75–81), 66% (95% CI: 58–73), 91% (95% CI: 87–94) and 52% (95% CI: 40–61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among people 60 years and older was 67% (95% CI: 52–77), 65% (95% CI: 48–76) and 83% (95% CI: 64–92) for Comirnaty, Vaxzevria and Spikevax, respectively. Comirnaty VE among those aged 30–59 years was 87% (95% CI: 83–89) at 14–29 days and 65% (95% CI: 56–71%) at ≥ 90 days between vaccination and onset of symptoms. Conclusions VE against symptomatic infection with the SARS-CoV-2 Delta variant varied among brands, ranging from 52% to 91%. While some waning of the vaccine effect may be present (sample size limited this analysis to only Comirnaty), protection was 65% at 90 days or more between vaccination and onset.