Estimating influenza latency and infectious period durations using viral excretion data.

Influenza infection natural history is often described as a progression through four successive stages: Susceptible-Exposed/Latent-Infectious-Removed (SEIR). The duration of each stage determines the average generation time, the time between infection of a case and infection of his/her infector. Recently, several authors have justified somewhat arbitrary choices in stage durations by how close the resulting generation time distribution was to viral excretion over time after infection. Taking this reasoning one step further, we propose that the viral excretion profile over time can be used directly to estimate the required parameters in an SEIR model. In our approach, the latency and infectious period distributions are estimated by minimizing the Kullback-Leibler divergence between the model-based generation time probability density function and the normalized average viral excretion profile. Following this approach, we estimated that the latency and infectious period last respectively 1.6 and 1.0 days on average using excretion profiles from experimental infections. Interestingly, we find that only 5% of cases are infectious for more than 2.9 days. We also discuss the consequences of these estimates for the evaluation of the efficacy of control measures such as isolation or treatment. We estimate that, under a best-case scenario where symptoms appear at the end of the latency period, index cases must be isolated or treated at most within 16h after symptoms onset to avoid 50% of secondary cases. This study provides the first estimates of latency and infectious period for influenza based directly on viral excretion data. It provides additional evidence that isolation or treatment of cases would be effective only if adopted shortly after symptoms onset, and shows that four days of isolation may be enough to avoid most transmissions.

Scenarios of diffusion and control of an influenza pandemic in Italy.

To predict the spread of a pandemic strain of influenza virus in Italy and the impact of control measures, we developed a susceptible-exposed, but not yet infectious-infectious-recovered, and no longer susceptible (SEIR) deterministic model with a stochastic simulation component. We modelled the impact of control measures such as vaccination, antiviral prophylaxis and social distancing measures. In the absence of control measures, the epidemic peak would be reached about 4 months after the importation of the first cases in Italy, and the epidemic would last about 7 months. When combined, the control measures would reduce the cumulative attack rate to about 4.2%, at best, although this would require an extremely high number of treated individuals. In accordance with international findings, our results highlight the need to respond to a pandemic with a combination of control measures.

Drosophila lethal giant larvae neoplastic mutant as a genetic tool for cancer modeling.

Drosophila lethal giant larvae (lgl) is a tumour suppressor gene whose function in establishing apical-basal cell polarity as well as in exerting proliferation control in epithelial tissues is conserved between flies and mammals. Individuals bearing lgl null mutations show a gradual loss of tissue architecture and an extended larval life in which cell proliferation never ceases and no differentiation occurs, resulting in prepupal lethality. When tissues from those individuals are transplanted into adult normal recipients, a subset of cells, possibly the cancer stem units, are again able to proliferate and give rise to metastases which migrate to distant sites killing the host. This phenotype closely resembles that of mammalian epithelial cancers, in which loss of cell polarity is one of the hallmarks of a malignant, metastatic behaviour associated with poor prognosis. Lgl protein shares with its human counterpart Human giant larvae-1 (Hugl-1) significant stretches of sequence similarity that we demonstrated to translate into a complete functional conservation, pointing out a role in cell proliferation control and tumorigenesis also for the human homologue. The functional conservation and the power of fly genetics, that allows the researcher to manipulate the fly genome at a level of precision that exceeds that of any other multicellular genetic system, make this Drosophila mutant a very suitable model in which to investigate the mechanisms underlying epithelial tumour formation, progression and metastatisation. In this review, we will summarise the results obtained in these later years using this model for the study of cancer biology. Moreover, we will discuss how recent advances in developmental genetics techniques have succeeded in enhancing the similarities between fly and human tumorigenesis, giving Drosophila a pivotal role in the study of such a complex genetic disease.

[Hypothyroidism and megacolon]. / Ipotiroidisomo e megacolon.

A 71 years old woman, affected by ischemic heart disease from the age of 50 and by chronic constipation was admitted to the emergency department for drowsiness, intense dyspnea and acute abdominal distension. Laparotomy evidenced a megacolon. Because of the age and sex of the patient the congenital form of the megacolon was ruled out. No one of the more common causes of megacolon was recognized, but a severe hypothyroldism and Hashimoto's thyroiditis was discovered. Treatment with levothyroxine caused a progressive improvement of the general condition of the patient and of the megacolon so that the authors hypothesize that the intestinal pseudo-occlusion was caused by the hypothyroidism. In this paper the authors make a thorough analysis of the literature about the association between hypothyroidism and megacolon. Although many hypothesis have been put forward about the possible pathogenetic association between these two diseases, until now no definitive result has been reached. The authors, moreover, hypothesize that the pleural and pericardial effusion and the peculiar metabolic state characterized by plasma hyponatremia and hyposmolarity, with a constant urinary hyperosmolarity, were also caused by hypothyroidism; in fact the clinical and metabolic conditions improved after levothyroxine therapy. In the end the authors discuss if it is preferable to use tetraiodothyronine or triIodothyronine for the treatment of intense hypothyroidism in a patient in critical clinical state.

Prevalence of hepatitis B virus markers among intravenous drug abusers in Stockholm: impact of heterosexual transmission.

In order to study the importance of sexual transmission of hepatitis B virus (HBV) among intravenous drug abusers (IVDAs), and from IVDAs to others, we consecutively interviewed 171 IVDAs detained at the Stockholm Remand Prison during 4 months in 1990. Sexual histories revealed that 77% reported > or = 3 sexual partners during the last 3 years, 64% had had a sexual partner who did not inject drugs, and 61% reported a prior STD. The prevalence of HBV markers was 75%. In a multiple logistic regression analysis, a high risk for HBV markers was associated with an increasing duration of drug abuse, a high prevalence of hepatitis A markers, and an increasing number of drug injecting sexual partners during the last 3 years, indicating that sexual transmission, along with sharing of needles, may contribute to the high prevalence of HBV markers within this group. It is suggested that an adequate sexual history must be obtained from IVDAs with acute viral hepatitis in order to identify sexual partners who should be offered postexposure prophylaxis, and that non-immune IVDAs should be vaccinated against viral hepatitis A and B.

Risk of pneumonia in patients previously treated in hospital for pneumonia.

Although elderly patients who are admitted to hospital for any disease have a higher risk of pneumonia subsequently, whether those treated in hospital for pneumonia are at even greater risk is unknown. Therefore we retrospectively assessed morbidity and mortality due to pneumonia after discharge in 573 consecutive patients admitted to hospital for pneumonia, gastrointestinal infection, renal infection, or erysipelas. Average follow-up was 34 months. The incidence rate for pneumonia was 5.45 times higher in the group of patients discharged after pneumonia than in the other groups combined (95% confidence interval 2.89-10.26; p less than 0.001), and this group also had more deaths due to pneumonia (p = 0.06). For patients 50 years or older Streptococcus pneumoniae is the main cause of pneumonia. Pneumococcal vaccination after hospital treatment for an episode of pneumonia might be a cost-effective means of preventing disease in this group.

Sexual behaviour related to the spread of sexually transmitted diseases--a population-based survey.

Behavioural patterns pertinent to the spread of sexually transmitted diseases (STD) were assessed in a random sample population study in Sweden. From a sample of 1150 individuals aged 16-31 years, 768 (68%) completed a questionnaire on past and present sexual contacts. Response rate was highest in youngest and oldest age groups. Median age at first intercourse was 16.4 years for women and 17.1 years for men; the woman's partner at first intercourse was a median of 2 years older; men chose partners of the same age for first intercourse. The time to second partner was a median of 2 years; number of lifetime partners increased with one new partner for 2.5 years. Condoms were more frequently used in younger age groups. In all age groups, 5-10% of individuals reported a high-risk behaviour for the spread of STDs.

Estimation of a preference matrix for women's choice of male sexual partner according to rate of partner change, using partner notification data.

Data from a study of partner notification for venereal chlamydial infection are used to estimate the contact preference matrix, according to sexual contact activity levels of the male partners, of young heterosexual women. A method for correcting data for the bias introduced by studying infected women only is presented. Results indicate that an overall proportional mixing model is not an adequate description of the mixing pattern.

The effect of structural behavior change on the spread of HIV in a one-sex population.

Within a preferred mixing type of model for the spread of HIV in a one-sex population, the effects of structural behavior change, that is movements of individuals from one activity class to another, with accompanying changes of contact pattern are investigated. It is concluded that such behavior change makes it more difficult for an epidemic to arise if the contact pattern is of the restricted type, whereas the effect is indeterminate in the proportional mixing case. Some of the problems in analyzing sexual activity data from a population within which this behavior change mechanism is at work are also commented upon.

Incubation time of AIDS: progression of disease in a cohort of HIV-infected homo- and bisexual men with known dates of infection.

The time from infection with HIV to symptoms and AIDS is an important parameter in describing the natural course of HIV infection. We here describe disease progression in a group of 389 homo- and bisexual men. Of these 102 had known dates of infection, and during an average follow-up time of 31 months (range 2-108), 28 of these progressed from being symptom-free (CDC group II and III) to having some symptom from CDC group IV; 7 progressed to AIDS. By life-table analysis, the estimated average time from seroconversion to first symptom is approximately 5 years and to AIDS approximately 8 years. Very few patients are diagnosed with AIDS the first 2 years after infection, but after that the risk seems to be 5-10% per year. Increasing use of anti-HIV medication will render studies of this kind difficult in the future.

Comparative studies of in vitro transformation by ethylene oxide and gamma-radiation of C3H/10T1/2 cells.

A dose-dependent transforming ability of the direct-acting alkylating agent, ethylene oxide (EtO), was demonstrated in C3H/10T1/2 mouse embryo fibroblasts. Morphologically transformed colonies were observed 5-6 weeks after the treatment with EtO. The transforming effectiveness of EtO was compared with that of gamma-radiation, and the rad-equivalence of EtO was calculated to be approximately 90 rad/mMh. This value is consistent with earlier estimates based on induced mutation in various biological systems and thus indicates the applicability of the C3H/10T1/2 cell system in the risk estimation of human exposure to genotoxic compounds.

Note on ethene and other low-molecular weight hydrocarbons in environmental tobacco smoke.

Levels of ethene and propene, together with those of some other light hydrocarbons (propane, butane, isobutane and ethyne), have been measured under realistic conditions in environmental tobacco smoke (ETS) as a step towards the elucidation of the sources of 2-hydroxyethyl and 2-hydroxypropyl adducts of hemoglobin observed in non-smokers. These adducts may reflect in vivo doses of carcinogenic epoxides that are metabolites of the respective alkenes. The data show that 2.0 mg ethene, 1.4 mg propene, and 0.7 mg propane together with smaller amounts of butane, isobutane and ethyne are released per cigarette smoked (0.66 g tobacco) of a common Swedish brand. The alkenes in ETS should be considered as contributing factors to a risk of systemic cancer from passive smoking. With regard to alkene intake, even a relatively mild exposure to ETS (2 cigarettes per h for 5 h per day in a 33 m3 room with one air change per hour is estimated to correspond to the active smoking of about one cigarette per day.

Incidence of symptoms and AIDS in 146 Swedish haemophiliacs and blood transfusion recipients infected with human immunodeficiency virus.

The times from infection with the human immuno-deficiency virus (HIV) to the onset of the first clinical symptom and the development of AIDS were studied prospectively in 98 haemophiliacs and 48 blood transfusion recipients infected with the virus. Patients were followed up for a median of 61 months after infection, the dates of infection being either known exactly or estimated from the interval between the last negative and first positive HIV antibody test result. The rate of progression to AIDS was significantly higher for the transfusion recipients than for the haemophiliacs. The difference in time to the occurrence of the first clinical symptom was less pronounced between the two groups, though pointing in the same direction. The results suggest that on average roughly half of all patients positive for HIV will develop some clinical sign or symptom within five to six years after infection.

HIV infectivity--the hepatitis B lesson.

The probability of acquiring an HIV infection through different types of risk behaviour is not well known. For prognoses on the future spread of the infection some knowledge of these probabilities is of vital importance. While they may be difficult to ascertain directly, comparison with better known diseases that are transmitted in a similar fashion might give some indication. Hepatitis B virus (HBV) shares many routes of transmission with HIV. We here propose a model, where the parallel seroconversion to HBV and HIV in a cohort of homosexual men is used to estimate the relative infectivities of the two diseases. For homosexual contacts HBV seems to be about 10 times as contagious as HIV.

The asymptotic final size distribution of reducible multitype Reed-Frost processes.

The asymptotic final size distribution of a multitype Reed-Frost process, a chain-binomial model for the spread of infection in a finite, closed multitype population, is derived in the case of reducible contact pattern between types. The results are obtained using techniques developed for the irreducible case.