The Design and Analysis of Partner Studies of HIV Transmission

Common goals in epidemiologic studies of infectious diseases include identification of the infectious agent, description of the modes of transmission and characterization of factors that influence the probability of transmission from infected to uninfected individuals. In the case of AIDS, the agent has been identified as the Human Immunodeficiency Virus (HIV), and transmission is known to occur through a variety of contact mechanisms including unprotected sexual intercourse, transfusion of infected blood products and sharing of needles in intravenous drug use. Relatively little is known about the probability of IV transmission associated with the various modes of contact, or the role that other cofactors play in promoting or suppressing transmission. Here, transmission probability refers to the probability that the virus is transmitted to a susceptible individual following exposure consisting of a series of potentially infectious contacts. The infectivity of HIV for a given route of transmission is defined to be the per contact probability of infection. Knowledge of infectivity and its relationship to other factors is important in understanding the dynamics of the AIDS epidemic and in suggesting appropriate measures to control its spread. The primary source of empirical data about infectivity comes from sexual partners of infected individuals. Partner studies consist of a series of such partnerships, usually heterosexual and monogamous, each composed of an initially infected "index case" and a partner who may or may not be infected by the time of data collection. However, because the infection times of both partners may be unknown and the history of contacts uncertain, any quantitative characterization of infectivity is extremely difficult. Thus, most statistical analyses of partner study data involve the simplifying assumption that infectivity is a constant common to all partnerships. The major objectives of this work are to describe and discuss the design and analysis of partner studies, providing a general statistical framework for investigations of infectivity and risk factors for HIV transmission. The development is largely based on three papers: Jewell and Shiboski (1990), Kim and Lagakos (1990), and Shiboski and Jewell (1992).

Microarray based study on virulence-associated genes and resistance determinants of Staphylococcus aureus isolates from cattle

Staphylococcus aureus is a common pathogen which can colonise and infect not only man, but also domestic animals. Especially, infection of cattle is of high economic relevance as S. aureus is an important causal agent of bovine mastitis. In the present contribution, a DNA microarray was applied for the study of 144 different gene targets, including resistance genes and genes encoding exotoxins, in S. aureus isolated from cows. One hundred and twenty-eight isolates from Germany and Switzerland were tested. These isolates were assigned to 20 different strains and nine clonal complexes. The majority of isolates belonged either to apparently closely related clonal complexes 8, 25, and 97 (together 34.4%) or were related to the sequenced bovine strain RF122 (48.4%). Notable characteristics of S. aureus of bovine origin are the carriage of intact haemolysin beta (in 82% of isolates tested), the absence of staphylokinase (in 89.1%), the presence of allelic variants of several exotoxins such as toxic shock syndrome toxin and enterotoxin N, and the occurrence of the leukocidin lukF-P83/lukM (in 53.1%). Two isolates were methicillin-resistant S. aureus (MRSA). One of them was a clonal complex 8 MRSA related to the epidemic MRSA strain Irish 01. The other one belonged to ST398/spa-type 34 resembling a newly emerging MRSA strain which has been described to occur in humans as well as in domestic animals. The presence of these two strains highlights the possibility of transfers of S. aureus strains between different host species.

Human alveolar echinococcosis after fox population increase, Switzerland

We analyzed databases spanning 50 years, which included retrospective alveolar echinococcosis (AE) case finding studies and databases of the 3 major centers for treatment of AE in Switzerland. A total of 494 cases were recorded. Annual incidence of AE per 100,000 population increased from 0.12-0.15 during 1956-1992 and a mean of 0.10 during 1993-2000 to a mean of 0.26 during 2001-2005. Because the clinical stage of the disease did not change between observation periods, this increase cannot be explained by improved diagnosis. Swiss hunting statistics suggested that the fox population increased 4-fold from 1980 through 1995 and has persisted at these higher levels. Because the period between infection and development of clinical disease is long, the increase in the fox population and high Echinococcus multilocularis prevalence rates in foxes in rural and urban areas may have resulted in an emerging epidemic of AE 10-15 years later.

No temporal association between influenza outbreaks and invasive pneumococcal infections

OBJECTIVE: To assess whether the influenza peak in populations precedes the annual peak for invasive pneumococcal infections (IPI) in winter. DESIGN: Ecological study. Active surveillance data on influenza A and IPI in children up to 16 years of age collected from 1997 to 2003 were analysed. SETTING: Paediatric hospitals in Germany. Patients: Children under 16 years of age. RESULTS: In all years under study, the influenza A season did not appear to affect the IPI season (p = 0.49). Specifically, the influenza peak never preceded the IPI peak. CONCLUSION: On a population level there was no indication that the annual influenza epidemic triggered the winter increase in the IPI rate or the peak of the IPI distribution in children.

A homologue of aliB is found in the capsule region of nonencapsulated Streptococcus pneumoniae

The epidemiology, phylogeny, and biology of nonencapsulated Streptococcus pneumoniae are largely unknown. Increased colonization capacity and transformability are, however, intriguing features of these pneumococci and play an important role. Twenty-seven nonencapsulated pneumococci were identified in a nationwide collection of 1,980 nasopharyngeal samples and 215 blood samples obtained between 1998 and 2002. On the basis of multilocus sequence typing and capsule region analysis we divided the nonencapsulated pneumococci into two groups. Group I was closely related to encapsulated strains. Group II had a clonal population structure, including two geographically widespread clones able to cause epidemic conjunctivitis and invasive diseases. Group II strains also carried a 1,959-bp homologue of aliB (aliB-like ORF 2) in the capsule region, which was highly homologous to a sequence in the capsule region of Streptococcus mitis. In addition, strains of the two major clones in group II had an additional sequence, aliB-like ORF 1 (1,968 to 2,004 bp), upstream of aliB-like ORF 2. Expression of aliB-like ORF 1 was detected by reverse transcription-PCR, and the corresponding RNA was visualized by Northern blotting. A gene fragment homologous to capN of serotypes 33 and 37 suggests that group II strains were derived from encapsulated pneumococci some time ago. Therefore, loss of capsule expression in vivo was found to be associated with the importation of one or two aliB homologues in some nonencapsulated pneumococci.

Care of the bariatric surgery patient in the emergency department

Obesity has reached epidemic proportions in the United States, with an estimated 50% of adults meeting the definition of being overweight. As this condition has become more prevalent, bariatric surgery has become an increasingly accepted form of treatment of the severely obese. Patients who have had bariatric surgery are presenting more commonly to Emergency Departments as a result. This article will review the most common bariatric surgery procedures, the complications that can arise post-operatively, and the approach to the assessment and management of the bariatric surgery patient in the Emergency Department.

An analysis of the spatial and temporal patterns of highly pathogenic avian influenza occurrence in Vietnam using national surveillance data

The objectives of this study were to describe the spatio-temporal pattern of an epidemic of highly pathogenic avian influenza (HPAI) in Vietnam and to identify potential risk factors for the introduction and maintenance of infection within the poultry population. The results indicate that during the time period 2004–early 2006 a sequence of three epidemic waves occurred in Vietnam as distinct spatial and temporal clusters. The risk of outbreak occurrence increased with a greater percentage of rice paddy fields, increasing domestic water bird and chicken density. It increased with reducing distance to higher population density aggregations, and in the third epidemic wave with increasing percentage of aquaculture. The findings indicate that agri-livestock farming systems involving domestic water birds and rice production in river delta areas are important for the maintenance and spread of infection. While the government’s control measures appear to have been effective in the South and Central parts of Vietnam, it is likely that in the North of Vietnam the vaccination campaign led to transmission of infection which was subsequently brought under control.

Nationwide surveillance of nasopharyngeal Streptococcus pneumoniae isolates from children with respiratory infection, Switzerland, 1998-1999

The surveillance of pneumococcal antibiotic resistance and serotype distribution is hampered by the relatively low numbers of invasive pneumococcal infections. In Switzerland, a nationwide sentinel surveillance network was used to assess antibiotic resistance and serotype distribution among 1179 pneumococcal isolates cultured from 2769 nasopharyngeal swabs obtained from outpatients with acute otitis media or pneumonia during 1998 and 1999. The proportion of penicillin-susceptible pneumococcal isolates overall (87%) and among infants <2 years old (81%) was comparable to that of invasive isolates (90% and 81%, respectively). The high number of nasopharyngeal isolates allowed for the detection of a rapid increase in the number of penicillin-nonsusceptible pneumococcal (PNSP) strains in the West region of Switzerland, partly because of an epidemic caused by the 19F clone of Streptococcus pneumoniae. Clustering of risk factors for the carriage of PNSP isolates further explained the geographic variation in resistance rates. The nationwide sentinel surveillance of nasopharyngeal pneumococcus proved to be valuable for the monitoring of antibiotic resistance, risk factors for carriage of PNSP isolates, and serotype distribution and for the detection of the emergence of a new epidemic clone.

[Bisexuality and AIDS. Implications for heterosexual HIV infections in women]

One of the possible pathways into heterosexual population is the transfer of HIV-virus from bisexual men to their female partners. Therefore sexual behaviour of HIV-positive and -negative bisexual men (n = 31) before and after Aids-disease was analysed. Prior to the Aids-epidemic promiscuous behavior towards male partners (about one female partner per year versus 10 male partners per year). Relatively common contacts to woman occurred within steady relationships. After contact with HIV-test and personal counselling sexual practice became significantly different. The number of female and male contacts was markedly reduced, especially female chance acquaintances were avoided; safer sex was preferred and readiness to inform female partners about bisexuality was increased. This study suggests that reduction of risk for HIV-infection of female partners by homosexual men can be achieved by means of a HIV-test and personal counselling, a possibility that should be considered in preventive concepts.

Regional comparisons of nano-mechanical properties of the human meniscus; structure and function

Osteoarthritis (OA) is a debilitating disease that is becoming more prevalent in today’s society. OA affects approximately 28 million adults in the United States alone and when present in the knee joint, usually leads to a total knee replacement. Numerous studies have been conducted to determine possible methods to halt the initiation of OA, but the structural integrity of the menisci has been shown have a direct effect on the progression of OA. Menisci are two C-shaped structures that are attached to the tibial plateau and aid in facilitating proper load transmission within the knee. The meniscal cross-section is wedge-like to fit the contour of the femoral condyles and help attenuate stresses on the tibial plateau. While meniscal tears are common, only the outer 1/3 of the meniscus is vascularized and has the capacity to heal, hence tears of the inner 2/3rds are generally treated via meniscectomy, leading to OA. To help combat this OA epidemic, an effective biomimetric meniscal replacement is needed. Numerous mechanical and biochemical studies have been conducted on the human meniscus, but very little is known about the mechanical properties on the nano-scale and how meniscal constituents are distributed in the meniscal cross-section. The regional (anterior, central and posterior) nano-mechanical properties of the meniscal superficial layers (both tibial and femoral contacting) and meniscal deep zone were investigated via nanoindentation to examine the regional inhomogeneity of both the lateral and medial menisci. Additionally, these results were compared to quantitative histological values to better formulate a structure-function relationship on the nano-scale. These data will prove imperative for further advancements of a tissue engineered meniscal replacement.

A 5-year comparison of performance of sentinel and mandatory notification surveillance systems for measles in Switzerland

A sensitive, specific and timely surveillance is necessary to monitor progress towards measles elimination. We evaluated the performance of sentinel and mandatory-based surveillance systems for measles in Switzerland during a 5-year period by comparing 145 sentinel and 740 mandatory notified cases. The higher proportion of physicians who reported at least one case per year in the sentinel system suggests underreporting in the recently introduced mandatory surveillance for measles. Accordingly, the latter reported 2-36-fold lower estimates for incidence rates than the sentinel surveillance. However, these estimates were only 0.6-12-fold lower when we considered confirmed cases alone, which indicates a higher specificity of the mandatory surveillance system. In contrast, the sentinel network, which covers 3.5% of all outpatient consultations, detected only weakly and late a major national measles epidemic in 2003 and completely missed 2 of 10 cantonal outbreaks. Despite its better timeliness and greater sensitivity in case detection, the sentinel system, in the current situation of low incidence, is insufficient to perform measles control and to monitor progress towards elimination.

Automatic Food Intake Assessment Using Camera Phones

Obesity is becoming an epidemic phenomenon in most developed countries. The fundamental cause of obesity and overweight is an energy imbalance between calories consumed and calories expended. It is essential to monitor everyday food intake for obesity prevention and management. Existing dietary assessment methods usually require manually recording and recall of food types and portions. Accuracy of the results largely relies on many uncertain factors such as user's memory, food knowledge, and portion estimations. As a result, the accuracy is often compromised. Accurate and convenient dietary assessment methods are still blank and needed in both population and research societies. In this thesis, an automatic food intake assessment method using cameras, inertial measurement units (IMUs) on smart phones was developed to help people foster a healthy life style. With this method, users use their smart phones before and after a meal to capture images or videos around the meal. The smart phone will recognize food items and calculate the volume of the food consumed and provide the results to users. The technical objective is to explore the feasibility of image based food recognition and image based volume estimation. This thesis comprises five publications that address four specific goals of this work: (1) to develop a prototype system with existing methods to review the literature methods, find their drawbacks and explore the feasibility to develop novel methods; (2) based on the prototype system, to investigate new food classification methods to improve the recognition accuracy to a field application level; (3) to design indexing methods for large-scale image database to facilitate the development of new food image recognition and retrieval algorithms; (4) to develop novel convenient and accurate food volume estimation methods using only smart phones with cameras and IMUs. A prototype system was implemented to review existing methods. Image feature detector and descriptor were developed and a nearest neighbor classifier were implemented to classify food items. A reedit card marker method was introduced for metric scale 3D reconstruction and volume calculation. To increase recognition accuracy, novel multi-view food recognition algorithms were developed to recognize regular shape food items. To further increase the accuracy and make the algorithm applicable to arbitrary food items, new food features, new classifiers were designed. The efficiency of the algorithm was increased by means of developing novel image indexing method in large-scale image database. Finally, the volume calculation was enhanced through reducing the marker and introducing IMUs. Sensor fusion technique to combine measurements from cameras and IMUs were explored to infer the metric scale of the 3D model as well as reduce noises from these sensors.

Effects of four-week high-fructose diet on gene expression in skeletal muscle of healthy men

AIMS: A high-fructose diet (HFrD) may play a role in the obesity and metabolic disorders epidemic. In rodents, HFrD leads to insulin resistance and ectopic lipid deposition. In healthy humans, a four-week HFrD alters lipid homoeostasis, but does not affect insulin sensitivity or intramyocellular lipids (IMCL). The aim of this study was to investigate whether fructose may induce early molecular changes in skeletal muscle prior to the development of whole-body insulin resistance. METHODS: Muscle biopsies were taken from five healthy men who had participated in a previous four-week HFrD study, during which insulin sensitivity (hyperinsulinaemic euglycaemic clamp), and intrahepatocellular lipids and IMCL were assessed before and after HFrD. The mRNA concentrations of 16 genes involved in lipid and carbohydrate metabolism were quantified before and after HFrD by real-time quantitative PCR. RESULTS: HFrD significantly (P<0.05) increased stearoyl-CoA desaturase-1 (SCD-1) (+50%). Glucose transporter-4 (GLUT-4) decreased by 27% and acetyl-CoA carboxylase-2 decreased by 48%. A trend toward decreased peroxisomal proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) was observed (-26%, P=0.06). All other genes showed no significant changes. CONCLUSION: HFrD led to alterations of SCD-1, GLUT-4 and PGC-1alpha, which may be early markers of insulin resistance.

Mumps

Mumps is a common childhood infection caused by the mumps virus. The hallmark of infection is swelling of the parotid gland. Aseptic meningitis and encephalitis are common complications of mumps together with orchitis and oophoritis, which can arise in adult men and women, respectively; other complications include deafness and pancreatitis. Clinical diagnosis can be based on the classic parotid swelling; however, this feature is not present in all cases of mumps and can also occur in various other disorders. Laboratory diagnosis is based on isolation of virus, detection of viral nucleic acid, or serological confirmation (generally presence of IgM mumps antibodies). Mumps is vaccine-preventable, and one dose of mumps vaccine is about 80% effective against the disease. Routine vaccination has proven highly effective in reducing the incidence of mumps, and is presently used by most developed countries; however, there have been outbreaks of disease in vaccinated populations. In 2005, a large epidemic peaked in the UK, and in 2006 the American midwest had several outbreaks. In both countries, the largest proportion of cases was in young adults. In the UK, susceptible cohorts too old to have been vaccinated and too young to have been exposed to natural infections were the primary cause of the mumps epidemic. In the USA, effectiveness and uptake in combination appear not to have been sufficient to obtain herd immunity for mumps in populations such as college students.

Fulminant liver failure after vancomycin in a sulfasalazine-induced DRESS syndrome: fatal recurrence after liver transplantation

DRESS syndrome (drug rash with eosinophilia and systemic symptoms) is a rare drug hypersensitivity reaction with a significant mortality. We describe a 60-year-old man with polyarthritis treated with sulfasalazine who developed DRESS and fulminant liver failure after additional vancomycin treatment. Liver histology revealed infiltration of granzymeB+ CD3+ lymphocytes in close proximity to apoptotic hepatocytes. After a superurgent liver transplantation and initial recovery, the patient developed recurrent generalized exanthema and eosinophilia, but only moderate hepatitis. Histology showed infiltration of FasL+ lymphocytes and eosinophils in the transplanted liver. Treatment with high-dose methylprednisolone was unsuccessful. Postmortem examination revealed extensive necrosis of the liver transplant. This case report illustrates that patients with DRESS may develop fulminant liver failure and that DRESS recurrence can recur in the transplanted liver. Histological and immunological investigations suggest an important role of granzymeB and FasL mediated cell death in DRESS associated hepatitis.