Assessment of the severity of Ebola virus disease in Sierra Leone in 2014–2015

The current Ebola virus disease (EVD) epidemic in West Africa is unprecedented in scale, and Sierra Leone is the most severely affected country. The case fatality risk (CFR) and hospitalization fatality risk (HFR) were used to characterize the severity of infections in confirmed and probable EVD cases in Sierra Leone. Proportional hazards regression models were used to investigate factors associated with the risk of death in EVD cases. In total, there were 17 318 EVD cases reported in Sierra Leone from 23 May 2014 to 31 January 2015. Of the probable and confirmed EVD cases with a reported final outcome, a total of 2536 deaths and 886 recoveries were reported. CFR and HFR estimates were 74·2% [95% credibility interval (CrI) 72·6–75·5] and 68·9% (95% CrI 66·2–71·6), respectively. Risks of death were higher in the youngest (0–4 years) and oldest (≥60 years) age groups, and in the calendar month of October 2014. Sex and occupational status did not significantly affect the mortality of EVD. The CFR and HFR estimates of EVD were very high in Sierra Leone.

Spatiotemporal clustering analysis and risk assessments of human cutaneous anthrax in China, 2005–2012

Objective To investigate the epidemic characteristics of human cutaneous anthrax (CA) in China, detect the spatiotemporal clusters at the county level for preemptive public health interventions, and evaluate the differences in the epidemiological characteristics within and outside clusters. Methods CA cases reported during 2005–2012 from the national surveillance system were evaluated at the county level using space-time scan statistic. Comparative analysis of the epidemic characteristics within and outside identified clusters was performed using using the χ2 test or Kruskal-Wallis test. Results The group of 30–39 years had the highest incidence of CA, and the fatality rate increased with age, with persons ≥70 years showing a fatality rate of 4.04%. Seasonality analysis showed that most of CA cases occurred between May/June and September/October of each year. The primary spatiotemporal cluster contained 19 counties from June 2006 to May 2010, and it was mainly located straddling the borders of Sichuan, Gansu, and Qinghai provinces. In these high-risk areas, CA cases were predominantly found among younger, local, males, shepherds, who were living on agriculture and stockbreeding and characterized with high morbidity, low mortality and a shorter period from illness onset to diagnosis. Conclusion CA was geographically and persistently clustered in the Southwestern China during 2005–2012, with notable differences in the epidemic characteristics within and outside spatiotemporal clusters; this demonstrates the necessity for CA interventions such as enhanced surveillance, health education, mandatory and standard decontamination or disinfection procedures to be geographically targeted to the areas identified in this study.

Agricultural intensification, priming for persistence and the emergence of Nipah virus: a lethal bat-borne zoonosis

Emerging zoonoses threaten global health, yet the processes by which they emerge are complex and poorly understood. Nipah virus (NiV) is an important threat owing to its broad host and geographical range, high case fatality, potential for human-to-human transmission and lack of effective prevention or therapies. Here, we investigate the origin of the first identified outbreak of NiV encephalitis in Malaysia and Singapore. We analyse data on livestock production from the index site (a commercial pig farm in Malaysia) prior to and during the outbreak, on Malaysian agricultural production, and from surveys of NiV's wildlife reservoir (flying foxes). Our analyses suggest that repeated introduction of NiV from wildlife changed infection dynamics in pigs. Initial viral introduction produced an explosive epizootic that drove itself to extinction but primed the population for enzootic persistence upon reintroduction of the virus. The resultant within-farm persistence permitted regional spread and increased the number of human infections. This study refutes an earlier hypothesis that anomalous El Nino Southern Oscillation-related climatic conditions drove emergence and suggests that priming for persistence drove the emergence of a novel zoonotic pathogen. Thus, we provide empirical evidence for a causative mechanism previously proposed as a precursor to widespread infection with H5N1 avian influenza and other emerging pathogens.

Yield losses in grain sorghum due to rust infection

Although rust (caused by Puccinia purpurea) is a common disease in Australian grain sorghum crops, particularly late in the growing season (April onwards), its potential to reduce yield has not been quantified. Field trials were conducted in Queensland between 2003 and 2005 to evaluate the effect of sorghum rust on grain yield of two susceptible sorghum hybrids (Tx610 and Pride). Rust was managed from 28-35 days after sowing until physiological maturity by applying oxycarboxin (1 kg active ingredient/100 L of water/ha) every 10 days. When data were combined for the hybrids, yield losses ranged from 13.1% in 2005 to 3.2% in 2003 but differences in yield the between sprayed and unsprayed treatments were statistically significant (P a parts per thousand currency signaEuro parts per thousand 0.05) only in 2005. Final area under the disease progress curve (AUDPC) values reflected the yield losses in each year. The higher yield loss in 2005 can be attributed primarily to the early development of the rust epidemic and the higher inoculum levels in spreader plots at the time of planting of the trials.

A field investigation into a suspected outbreak of pyrrolizidine alkaloid toxicosis in horses in western Queensland

A disease outbreak investigation was conducted in western Queensland to investigate a rare suspected outbreak of pyrrolizidine alkaloid (PA) toxicosis in horses. Thirty five of 132 horses depastured on five properties on the Mitchell grass plains of western Queensland died in the first six months of 2010. Clinical–pathological findings were consistent with PA toxicosis. A local variety of Crotalaria medicaginea was the only hepatotoxic plant found growing on affected properties. Pathology reports and departure and arrival dates of two brood mares provided evidence of a pre wet season exposure period. All five affected properties experienced a very dry spring and early summer preceded by a large summer wet season. The outbreak was characterised as a point epidemic with a sudden peak of deaths in March followed by mortalities steadily declining until the end of June. The estimated morbidity (serum IGG > 50 IU/L) rate was 76%. Average crude mortality was 27% but higher in young horses (67%) and brood mares (44%). Logistic regression analysis showed that young horses and brood mares and those grazing denuded pastures in December were most strongly associated with dying whereas those fed hay and/or grain based supplements were less likely to die. This is the first detailed study of an outbreak of PA toxicosis in central western Queensland and the first to provide evidence that environmental determinants were associated with mortality, that the critical exposure period was towards the end of the dry season, that supplementary feeding is protective and that denuded pastures and the horses physiological protein requirement are risk factors.

Methicillin-resistant Staphylococcus aureus in Finland: recent changes in the epidemiology, long-term facility aspects, and phenotypic and molecular detection of isolates

Staphylococcus aureus is one of the most important bacteria that cause disease in humans, and methicillin-resistant S. aureus (MRSA) has become the most commonly identified antibiotic-resistant pathogen in many parts of the world. MRSA rates have been stable for many years in the Nordic countries and the Netherlands with a low MRSA prevalence in Europe, but in the recent decades, MRSA rates have increased in those low-prevalence countries as well. MRSA has been established as a major hospital pathogen, but has also been found increasingly in long-term facilities (LTF) and in communities of persons with no connections to the health-care setting. In Finland, the annual number of MRSA isolates reported to the National Infectious Disease Register (NIDR) has constantly increased, especially outside the Helsinki metropolitan area. Molecular typing has revealed numerous outbreak strains of MRSA, some of which have previously been associated with community acquisition. In this work, data on MRSA cases notified to the NIDR and on MRSA strain types identified with pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and staphylococcal cassette chromosome mec (SCCmec) typing at the National Reference Laboratory (NRL) in Finland from 1997 to 2004 were analyzed. An increasing trend in MRSA incidence in Finland from 1997 to 2004 was shown. In addition, non-multi-drug resistant (NMDR) MRSA isolates, especially those resistant only to methicillin/oxacillin, showed an emerging trend. The predominant MRSA strains changed over time and place, but two internationally spread epidemic strains of MRSA, FIN-16 and FIN-21, were related to the increase detected most recently. Those strains were also one cause of the strikingly increasing invasive MRSA findings. The rise of MRSA strains with SCCmec types IV or V, possible community-acquired MRSA was also detected. With questionnaires, the diagnostic methods used for MRSA identification in Finnish microbiology laboratories and the number of MRSA screening specimens studied were reviewed. Surveys, which focused on the MRSA situation in long-term facilities in 2001 and on the background information of MRSA-positive persons in 2001-2003, were also carried out. The rates of MRSA and screening practices varied widely across geographic regions. Part of the NMDR MRSA strains could remain undetected in some laboratories because of insufficient diagnostic techniques used. The increasing proportion of elderly population carrying MRSA suggests that MRSA is an emerging problem in Finnish long-term facilities. Among the patients, 50% of the specimens were taken on a clinical basis, 43% on a screening basis after exposure to MRSA, 3% on a screening basis because of hospital contact abroad, and 4% for other reasons. In response to an outbreak of MRSA possessing a new genotype that occurred in a health care ward and in an associated nursing home of a small municipality in Northern Finland in autumn 2003, a point-prevalence survey was performed six months later. In the same study, the molecular epidemiology of MRSA and methicillin-sensitive S. aureus (MSSA) strains were also assessed, the results to the national strain collection compared, and the difficulties of MRSA screening with low-level oxacillin-resistant isolates encountered. The original MRSA outbreak in LTF, which consisted of isolates possessing a nationally new PFGE profile (FIN-22) and internationally rare MLST type (ST-27), was confined. Another previously unrecognized MRSA strain was found with additional screening, possibly indicating that current routine MRSA screening methods may be insufficiently sensitive for strains possessing low-level oxacillin resistance. Most of the MSSA strains found were genotypically related to the epidemic MRSA strains, but only a few of them had received the SCCmec element, and all those strains possessed the new SCCmec type V. In the second largest nursing home in Finland, the colonization of S. aureus and MRSA, and the role of screening sites along with broth enrichment culture on the sensitivity to detect S. aureus were studied. Combining the use of enrichment broth and perineal swabbing, in addition to nostrils and skin lesions swabbing, may be an alternative for throat swabs in the nursing home setting, especially when residents are uncooperative. Finally, in order to evaluate adequate phenotypic and genotypic methods needed for reliable laboratory diagnostics of MRSA, oxacillin disk diffusion and MIC tests to the cefoxitin disk diffusion method at both +35°C and +30°C, both with or without an addition of sodium chloride (NaCl) to the Müller Hinton test medium, and in-house PCR to two commercial molecular methods (the GenoType® MRSA test and the EVIGENETM MRSA Detection test) with different bacterial species in addition to S. aureus were compared. The cefoxitin disk diffusion method was superior to that of oxacillin disk diffusion and to the MIC tests in predicting mecA-mediated resistance in S. aureus when incubating at +35°C with or without the addition of NaCl to the test medium. Both the Geno Type® MRSA and EVIGENETM MRSA Detection tests are usable, accurate, cost-effective, and sufficiently fast methods for rapid MRSA confirmation from a pure culture.

Co-distribution and co-infection of chikungunya and dengue viruses

BACKGROUND Chikungunya and dengue infections are spatio-temporally related. The current review aims to determine the geographic limits of chikungunya, dengue and the principal mosquito vectors for both viruses and to synthesise current epidemiological understanding of their co-distribution. METHODS Three biomedical databases (PubMed, Scopus and Web of Science) were searched from their inception until May 2015 for studies that reported concurrent detection of chikungunya and dengue viruses in the same patient. Additionally, data from WHO, CDC and Healthmap alerts were extracted to create up-to-date global distribution maps for both dengue and chikungunya. RESULTS Evidence for chikungunya-dengue co-infection has been found in Angola, Gabon, India, Madagascar, Malaysia, Myanmar, Nigeria, Saint Martin, Singapore, Sri Lanka, Tanzania, Thailand and Yemen; these constitute only 13 out of the 98 countries/territories where both chikungunya and dengue epidemic/endemic transmission have been reported. CONCLUSIONS Understanding the true extent of chikungunya-dengue co-infection is hampered by current diagnosis largely based on their similar symptoms. Heightened awareness of chikungunya among the public and public health practitioners in the advent of the ongoing outbreak in the Americas can be expected to improve diagnostic rigour. Maps generated from the newly compiled lists of the geographic distribution of both pathogens and vectors represent the current geographical limits of chikungunya and dengue, as well as the countries/territories at risk of future incursion by both viruses. These describe regions of co-endemicity in which lab-based diagnosis of suspected cases is of higher priority.

Risk assessment for airborne infectious diseases between natural ventilation and split-system air conditioner in a university classroom

Indoor air quality is a critical factor in the classroom due to high people concentration in a unique space. Indoor air pollutant might increase the chance of both long and short-term health problems among students and staff, reduce the productivity of teachers and degrade the student’s learning environment and comfort. Adequate air distribution strategies may reduce risk of infection in classroom. So, the purpose of air distribution systems in a classroom is not only to maximize conditions for thermal comfort, but also to remove indoor contaminants. Natural ventilation has the potential to play a significant role in achieving improvements in IAQ. The present study compares the risk of airborne infection between Natural Ventilation (opening windows and doors) and a Split-System Air Conditioner in a university classroom. The Wells-Riley model was used to predict the risk of indoor airborne transmission of infectious diseases such as influenza, measles and tuberculosis. For each case, the air exchange rate was measured using a CO2 tracer gas technique. It was found that opening windows and doors provided an air exchange rate of 2.3 air changes/hour (ACH), while with the Split System it was 0.6 ACH. The risk of airborne infection ranged between 4.24 to 30.86 % when using the Natural Ventilation and between 8.99 to 43.19% when using the Split System. The difference of airborne infection risk between the Split System and the Natural Ventilation ranged from 47 to 56%. Opening windows and doors maximize Natural Ventilation so that the risk of airborne contagion is much lower than with Split System.

Microbe-induced activation of inflammatory cytokine response in human cells

Human body is in continuous contact with microbes. Although many microbes are harmless or beneficial for humans, pathogenic microbes possess a threat to wellbeing. Antimicrobial protection is provided by the immune system, which can be functionally divided into two parts, namely innate and adaptive immunity. The key players of the innate immunity are phagocytic white blood cells such as neutrophils, monocytes, macrophages and dendritic cells (DCs), which constantly monitor the blood and peripheral tissues. These cells are armed for rapid activation upon microbial contact since they express a variety of microbe-recognizing receptors. Macrophages and DCs also act as antigen presenting cells (APCs) and play an important role in the development of adaptive immunity. The development of adaptive immunity requires intimate cooperation between APCs and T lymphocytes and results in microbe-specific immune responses. Moreover, adaptive immunity generates immunological memory, which rapidly and efficiently protects the host from reinfection. Properly functioning immune system requires efficient communication between cells. Cytokines are proteins, which mediate intercellular communication together with direct cell-cell contacts. Immune cells produce inflammatory cytokines rapidly following microbial contact. Inflammatory cytokines modulate the development of local immune response by binding to cell surface receptors, which results in the activation of intracellular signalling and modulates target cell gene expression. One class of inflammatory cytokines chemokines has a major role in regulating cellular traffic. Locally produced inflammatory chemokines guide the recruitment of effector cells to the site of inflammation during microbial infection. In this study two key questions were addressed. First, the ability of pathogenic and non-pathogenic Gram-positive bacteria to activate inflammatory cytokine and chemokine production in different human APCs was compared. In these studies macrophages and DCs were stimulated with pathogenic Steptococcus pyogenes or non-pathogenic Lactobacillus rhamnosus. The second aim of this thesis work was to analyze the role of pro-inflammatory cytokines in the regulation of microbe-induced chemokine production. In these studies bacteria-stimulated macrophages and influenza A virus-infected lung epithelial cells were used as model systems. The results of this study show that although macrophages and DCs share several common antimicrobial functions, these cells have significantly distinct responses against pathogenic and non-pathogenic Gram-positive bacteria. Macrophages were activated in a nearly similar fashion by pathogenic S. pyogenes and non-pathogenic L. rhamnosus. Both bacteria induced the production of similar core set of inflammatory chemokines consisting of several CC-class chemokines and CXCL8. These chemokines attract monocytes, neutrophils, dendritic cells and T cells. Thus, the results suggest that bacteria-activated macrophages efficiently recruit other effector cells to the site of inflammation. Moreover, macrophages seem to be activated by all bacteria irrespective of their pathogenicity. DCs, in contrast, were efficiently activated only by pathogenic S. pyogenes, which induced DC maturation and production of several inflammatory cytokines and chemokines. In contrast, L. rhamnosus-stimulated DCs matured only partially and, most importantly, these cells did not produce inflammatory cytokines or chemokines. L. rhamnosus-stimulated DCs had a phenotype of "semi-mature" DCs and this type of DCs have been suggested to enhance tolerogenic adaptive immune responses. Since DCs have an essential role in the development of adaptive immune response the results suggest that, in contrast to macrophages, DCs may be able to discriminate between pathogenic and non-pathogenic bacteria and thus mount appropriate inflammatory or tolerogenic adaptive immune response depending on the microbe in question. The results of this study also show that pro-inflammatory cytokines can contribute to microbe-induced chemokine production at multiple levels. S. pyogenes-induced type I interferon (IFN) was found to enhance the production of certain inflammatory chemokines in macrophages during bacterial stimulation. Thus, bacteria-induced chemokine production is regulated by direct (microbe-induced) and indirect (pro-inflammatory cytokine-induced) mechanisms during inflammation. In epithelial cells IFN- and tumor necrosis factor- (TNF-) were found to enhance the expression of PRRs and components of cellular signal transduction machinery. Pre-treatment of epithelial cells with these cytokines prior to virus infection resulted in markedly enhanced chemokine response compared to untreated cells. In conclusion, the results obtained from this study show that pro-inflammatory cytokines can enhance microbe-induced chemokine production during microbial infection by providing a positive feedback loop. In addition, pro-inflammatory cytokines can render normally low-responding cells to high chemokine producers via enhancement of microbial detection and signal transduction.

Molecular epidemiology of human rhinoviruses

The first part of this work investigates the molecular epidemiology of a human enterovirus (HEV), echovirus 30 (E-30). This project is part of a series of studies performed in our research team analyzing the molecular epidemiology of HEV-B viruses. A total of 129 virus strains had been isolated in different parts of Europe. The sequence analysis was performed in three different genomic regions: 420 nucleotides (nt) in the VP4/VP2 capsid protein coding region, the entire VP1 capsid protein coding gene of 876 nt, and 150 nt in the VP1/2A junction region. The analysis revealed a succession of dominant sublineages within a major genotype. The temporally earlier genotypes had been replaced by a genetically homogenous lineage that has been circulating in Europe since the late 1970s. The same genotype was found by other research groups in North America and Australia. Globally, other cocirculating genetic lineages also exist. The prevalence of a dominant genotype makes E-30 different from other previously studied HEVs, such as polioviruses and coxsackieviruses B4 and B5, for which several coexisting genetic lineages have been reported. The second part of this work deals with molecular epidemiology of human rhinoviruses (HRVs). A total of 61 field isolates were studied in the 420-nt stretch in the capsid coding region of VP4/VP2. The isolates were collected from children under two years of age in Tampere, Finland. Sequences from the clinical isolates clustered in the two previously known phylogenetic clades. Seasonal clustering was found. Also, several distinct serotype-like clusters were found to co-circulate during the same epidemic season. Reappearance of a cluster after disappearing for a season was observed. The molecular epidemiology of the analyzed strains turned out to be complex, and we decided to continue our studies of HRV. Only five previously published complete genome sequences of HRV prototype strains were available for analysis. Therefore, all designated HRV prototype strains (n=102) were sequenced in the VP4/VP2 region, and the possibility of genetic typing of HRV was evaluated. Seventy-six of the 102 prototype strains clustered in HRV genetic group A (HRV-A) and 25 in group B (HRV-B). Serotype 87 clustered separately from other HRVs with HEV species D. The field strains of HRV represented as many as 19 different genotypes, as judged with an approximate demarcation of a 20% nt difference in the VP4/VP2 region. The interserotypic differences of HRV were generally similar to those reported between different HEV serotypes (i.e. about 20%), but smaller differences, less than 10%, were also observed. Because some HRV serotypes are genetically so closely related, we suggest that the genetic typing be performed using the criterion "the closest prototype strain". This study is the first systematic genetic characterization of all known HRV prototype strains, providing a further taxonomic proposal for classification of HRV. We proposed to divide the genus Human rhinoviruses into HRV-A and HRV-B. The final part of the work comprises a phylogenetic analysis of a subset (48) of HRV prototype strains and field isolates (12) in the nonstructural part of the genome coding for the RNA-dependent RNA polymerase (3D). The proposed division of the HRV strains in the species HRV-A and HRV-B was also supported by 3D region. HRV-B clustered closer to HEV species B, C, and also to polioviruses than to HRV-A. Intraspecies variation within both HRV-A and HRV-B was greater in the 3D coding region than in the VP4/VP2 coding region, in contrast to HEV. Moreover, the diversity of HRV in 3D exceeded that of HEV. One group of HRV-A, designated HRV-A', formed a separate cluster outside other HRV-A in the 3D region. It formed a cluster also in the capsid region, but located within HRV-A. This may reflect a different evolutionary history of distinct genomic regions among HRV-A. Furthermore, the tree topology within HRV-A in the 3D region differed from that in the VP4/VP2, suggesting possible recombination events in the evolution of the strains. No conflicting phylogenies were observed in any of the 12 field isolates. Possible recombination was further studied using the Similarity and Bootscanning analyses of the complete genome sequences of HRV available in public databases. Evidence for recombination among HRV-A was found, as HRV2 and HRV39 showed higher similarity in the nonstructural part of the genome. Whether HRV2 and HRV39 strains - and perhaps also some other HRV-A strains not yet completely sequenced - are recombinants remains to be determined.

Liver fat in the metabolic syndrome and type 2 diabetes

Introduction: The epidemic of obesity has been accompanied by an increase in the prevalence of the metabolic syndrome, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). However, not all obese subjects develop these metabolic abnormalities. Hepatic fat accumulation is related to hepatic insulin resistance, which in turn leads to hyperglycemia, hypertriglyceridemia, and a low HDL cholesterol con-centration. The present studies aimed to investigate 1) how intrahepatic as compared to intramyocellular fat is related to insulin resistance in these tissues and to the metabolic syndrome (Study I); 2) the amount of liver fat in subjects with and without the metabolic syndrome, and which clinically available markers best reflect liver fat content (Study II); 3) the effect of liver fat on insulin clearance (Study III); 4) whether type 2 diabetic patients have more liver fat than age-, gender-, and BMI-matched non-diabetic subjects (Study IV); 5) how type 2 diabetic patients using exceptionally high doses of insulin respond to addition of a PPARγ agonist (Study V). Subjects and methods: The study groups consisted of 45 (Study I), 271 (Study II), and 80 (Study III) non-diabetic subjects, and of 70 type 2 diabetic patients and 70 matched control subjects (Study IV). In Study V, a total of 14 poorly controlled type 2 diabetic patients treated with high doses of insulin were studied before and after rosiglitazone treatment (8 mg/day) for 8 months. In all studies, liver fat content was measured by proton magnetic resonance spectroscopy, and sub-cutaneous and intra-abdominal fat content by MRI. In addition, circulating markers of insulin resistance and serum liver enzyme concentrations were determined. Hepatic (i.v. insulin infusion rate 0.3 mU/kg∙min combined with [3-3H]glucose, Studies I, III, and V) and muscle (1.0 mU/kg min, Study I) insulin sensitivities were measured by the euglycemic hyperinsulinemic clamp technique. Results: Fat accumulation in the liver rather than in skeletal muscle was associated with features of insulin resistance, i.e. increased fasting serum (fS) triglycerides and decreased fS-HDL cholesterol, and with hyperinsulinemia and low adiponectin concentrations (Study I). Liver fat content was 4-fold higher in subjects with as compared to those without the metabolic syndrome, independent of age, gender, and BMI. FS-C-peptide was the best correlate of liver fat (Study II). Increased liver fat was associated with both impaired insulin clearance and hepatic insulin resistance independent of age, gender, and BMI (Study III). Type 2 diabetic patients had 80% more liver fat than age-, weight-, and gender-matched non-diabetic subjects. At any given liver fat content, S-ALT underestimated liver fat in the type 2 diabetic patients as compared to the non-diabetic subjects (Study IV). In Study V, hepatic insulin sensitivity increased and glycemic control improved significantly during rosiglitazone treatment. This was associated with lowering of liver fat (on the average by 46%) and insulin requirements (40%). Conclusions: Liver fat is increased both in the metabolic syndrome and type 2 diabetes independent of age, gender, and BMI. A fatty liver is associated with both hepatic insulin resistance and impaired insulin clearance. Rosi-glitazone may be particularly effective in type 2 diabetic patients who are poorly controlled despite using high insulin doses.

HIV outbreak among injecting drug users in Finland

An HIV outbreak among Finnish injecting drug users (IDUs) occurred in 1998. By the end of 2005, 282 IDUs were in-fected, most of them by recombinant virus CRF01_AE of HIV. After a rapid spread, the outbreak subsided, and the prevalence of HIV among IDUs remained low (<2%). The purpose of the study was to describe the outbreak in order to recognise factors that have influenced the spread and restriction of the outbreak, and thus to find tools for HIV preven-tion. Data on Finnish IDUs newly diagnosed HIV-positive between 1998 and 2005 was collected through interviews and patient documents. Study I compared markers of disease progression between 93 Finnish IDUs and 63 Dutch IDUs. In study II, geographical spread of the HIV outbreak was examined and compared with the spatial distribution of employed males. In study III, risk behaviour data from interviews of 89 HIV-positive and 207 HIV-negative IDUs was linked, and prevalence and risk factors for unprotected sex were evaluated. In study IV, data on 238 newly diagnosed IDUs was combined with data on 675 sexually transmitted HIV cases, and risk factors for late HIV diagnosis (CD4 cell count <200/µL, or AIDS at HIV diagnosis) were analysed. Finnish IDUs infected with CRF01_AE exhibited higher viral loads than did Amsterdam IDUs infected with subtype B, but there was no difference in CD4 development. The Finnish IDU outbreak spread and was restricted socially in a marginalised IDU population and geographically in areas characterised by low proportions of employed males. Up to 40% of the cases in the two clusters outside the city centre had no contact with the centre, where needle exchange services were available since 1997. Up to 63% of HIV-positive and 80% of HIV-negative sexually active IDUs reported inconsistent condom use, which was associated with steady relationships and recent inpatient addiction care. Com-pared to other transmission groups, HIV-positive IDUs were diagnosed earlier in their infection. The proportion of late diagnosed HIV cases in all transmission groups was 23%, but was only 6% among IDUs diagnosed during the first four years of the epidemic. The high viral load in early HIV infection may have contributed to the rapid spread of recombinant virus in the Finnish outbreak. The outbreak was restricted to a marginalised IDU population, and limited spatially to local pockets of pov-erty. To prevent HIV among IDUs, these pockets should be recognised and reached early through outreach work and the distribution of needle exchange and other prevention activities. To prevent the sexual transmission of HIV among IDUs, prevention programmes should be combined with addiction care services and targeted at every IDU. The early detection of the outbreak and early implementation of needle exchange programmes likely played a crucial role in re-versing the IDU outbreak.

Japanese encephalitis: pathogenesis, prophylactics and therapeutics

Japanese encephalitis (JE) is one of the most dreaded mosquito-borne viral encephalitis known to afflict humans. The Japanese encephalitis virus (JEV) is a neurotropic flavivirus that affects the CNS, causing extensive damage that may lead to fatality in about one third of bpatients. Half of the survivors suffer from severe neuropshychiatric sequelae. With nearly 3 billion people living under the current JE-endemic region, recurring incidents of epidemic are being reported at regular intervals. With no established antiviral therapies against JE available, vaccination has been the only way of preventing JE. Two types of JE vaccines are currently in vogue although the safety of administering them is questionable, in certain individuals. Thus, there is a need to develop a safe, affordable and potent JE vaccine and this review addresses the current efforts in this direction. This review also focuses on the pathophysiology of JE and efforts towards a possible breakthrough in anti-JEV therapy.

Fertility in Namibia : Changes in fertility levels in North-Central Namibia 1960-2001, including an assessment of the impact of HIV

The aim of this study was to estimate the development of fertility in North-Central Namibia, former Ovamboland, from 1960 to 2001. Special attention was given to the onset of fertility decline and to the impact of the HIV epidemic on fertility. An additional aim was to introduce parish registers as a source of data for fertility research in Africa. Data used consisted of parish registers from Evangelical Lutheran congregations, the 1991 and 2001 Population and Housing Censuses, the 1992 and 2000 Namibia Demographic and Health Surveys, and the HIV sentinel surveillances of 1992-2004. Both period and cohort fertility were analysed. The P/F ratio method was used when analysing census data. The impact of HIV infection on fertility was estimated indirectly by comparing the fertility histories of women who died at an age of less than 50 years with the fertility of other women. The impact of the HIV epidemic on fertility was assessed both among infected women and in the general population. Fertility in the study population began to decline in 1980. The decline was rapid during the 1980s, levelled off in the early 1990s at the end of war of independence and then continued to decline until the end of the study period. According to parish registers, total fertility was 6.4 in the 1960s and 6.5 in the 1970s, and declined to 5.1 in the 1980s and 4.2 in the 1990s. Adjustment of these total fertility rates to correspond to levels of fertility based on data from the 1991 and 2001 censuses resulted in total fertility declining from 7.6 in 1960-79 to 6.0 in 1980-89, and to 4.9 in 1990-99. The decline was associated with increased age at first marriage, declining marital fertility and increasing premarital fertility. Fertility among adolescents increased, whereas the fertility of women in all other age groups declined. During the 1980s, the war of independence contributed to declining fertility through spousal separation and delayed marriages. Contraception has been employed in the study region since the 1980s, but in the early 1990s, use of contraceptives was still so limited that fertility was higher in North-Central Namibia than in other regions of the country. In the 1990s, fertility decline was largely a result of the increased prevalence of contraception. HIV prevalence among pregnant women increased from 4% in 1992 to 25% in 2001. In 2001, total fertility among HIV-infected women (3.7) was lower than that among other women (4.8), resulting in total fertility of 4.4 among the general population in 2001. The HIV epidemic explained more than a quarter of the decline in total fertility at population level during most of the 1990s. The HIV epidemic also reduced the number of children born by reducing the number of potential mothers. In the future, HIV will have an extensive influence on both the size and age structure of the Namibian population. Although HIV influences demographic development through both fertility and mortality, the effect through changes in fertility will be smaller than the effect through mortality. In the study region, as in some other regions of southern Africa, a new type of demographic transition is under way, one in which population growth stagnates or even reverses because of the combined effects of declining fertility and increasing mortality, both of which are consequences of the HIV pandemic.

Death, Ancestors, and HIV/AIDS among the Akan of Ghana

This is a study of crises caused by HIV/AIDS among the Akan of Ghana. It creates more awareness about the epidemic and has indicated other possible paths for campaign strategies. The pandemic has many devastating consequences; yet new infections are recorded daily despite campaigns against the disease. The search for therapy often sees the use of multiple outlets, which expresses Ghana's pluralistic medical system based on Kleinman's sector analytical model involving Western medicine, self-therapy, and folk healing. But it also leaves individuals and kin members in financial quandary. The fieldwork for this study is mainly through participant observation lasting 13 months (February 2003 to March 2004) among the Akan; in addition, some archival materials have been used. The Akan people live in the coastal south and forest zone of Ghana. Every Akan village or town is made up of corporate lineages, and social organisation is based on matrilineal descent. The society is holistic because the matrilineages seek the welfare of all their members. Meyer Fortes, R. S. Rattray and others on the Akan noticed this encompassing nature in the lineage organisation; but they did not make it salient (or failed to notice it) during illness, efforts for healing, and the care of the sick member. HIV/AIDS is an illness which shows the encompassing nature of the Akan matrilineage. It also reveals many contradictions in the group, viz. stigmatisation, abandonment, and attitudes that do not express altruism in a group expected to be closely-knit based on members' belief that they are of the 'same blood'. The crises have been analyzed in the total social system because the disease creates breaches at various levels of social interaction. An analysis of crises in a group is not far-fetched; Victor Turner has shown the way among the Ndembu and has revealed the contraditions in the seemingly uneventful life in the group. This study has identified that in dealing with HIV/AIDS patients and crises about the disease we are dealing with 'holistic' patients. Their cases produce many changes in the matrilineal structure--many orphans are being created and the care of patients is increasingly falling on the elderly. HIV/AIDS also challenges Akan cosmology because, for example, an AIDS death in local notions is a 'bad' demise which fails to produce ancestors who reproduce the society through reincarnation. Campaigns could emphasize this notion. The study begins with a description of the holistic nature of Akan matriliny, and the patients have been described as 'holistic' because their crises affect other people in the holistic society. Chapter 2 discusses the importance of ancestors as the starting points for social order who are constantly revered (in rites invoving the chief, Chapter 4). Chapter 3 focuses on funerals as an important social performance for the welfare of the dead and the living. Chapter 5 concentrates on HIV/AIDS as an illness threat marked by dominant discourses such as poverty, sexuality, migration, and condom use. Chapter 6 analyzes the attempts for therapy, and traditional healers' claims to have a cure. The efforts for therapy continues with spiritual church healing in Chapter 7, and chapter 8 is devoted to care of the patients and its inherent crises. Chapter 9 analyzes the effects of HIV/AIDS afflictions and AIDS deaths on the matrilineal group and in society. The study ends with a short part, devoted to Recommendations based on the findings in this investigation.