Human cancer from environmental pollutants: the epidemiological evidence

An increased risk of mesothelioma has been reported among individuals experiencing residential exposure to asbestos, while results for lung cancer are less consistent. Several studies have reported an increased risk of lung cancer risk from outdoor air pollution: on the basis of the results of the largest study, the proportion of lung cancers attributable to urban air pollution in Europe can be as high as 10.7%. A causal association has been established between second-hand tobacco smoking and lung cancer, which may be responsible for 1.6% of lung cancers. Radon is another carcinogen present in indoor air, which may be responsible for 4.5% of lung cancers. An increased risk of bladder might be due to water chlorination by-products. The available evidence on cancer risk following exposure to other environmental pollutants, including, pesticides, dioxins and electro-magnetic fields, is inconclusive.     

Immune responses induced by intranasal imiquimod and implications for therapeutics in rhinovirus infections

Notwithstanding the progress recently made in immunology and virology, there is yet no effective, specific treatment for the common cold. Symptomatic treatment is minimally effective. An anecdotal report of rapid clearing of the common cold of recent onset after intranasal application of imiquimod in several subjects by one of the authors, made us test the hypothesis that this treatment works through the secretion of interferon by the nasal mucosa. We decided to do an animal study in primates (Indian Macaca Mulata): 5 treatment and 3 control animals were used. Imiquimod or placebo was massaged into the nares of the animals and periodic samples of post-nasal fluid were taken and measurements for Interferon alpha (IFNalpha) and Tumor Necrosis Factor alpha (TNFalpha) were made by ELISA methods, and kinetic studies. mRNA IFNalpha was also isolated and analyzed by quantitative competitive RT-PCR. The internal standard was constructed to be complementary to and compete with oligonucleotide primers and for amplification of target sequences. One intranasal application of imiquimod rapidly (1-4 Hours) induced high levels of mRNA for IFNalpha, and minimal levels in the control animals. Rapid induction of INFalpha, and proportional increase of TNFalpha sustained for 4 and 6 hours respectively were noted. No adverse reactions to treatment were found in macaques during this short period of intranasal imiquimod usage (except in one macaque with a short period of lacrimation). No animal had cytotoxic effects when examined at 6 hr, 12 hr, 24 hr or 48 hr, except one animal, which had an episode of lacrimation for 6 hr post treatment. Thus both safety and efficacy of short treatment with imiquimod is proven in this animal model. Proof of principle for intranasal treatment of the common cold with imiquimod is shown. We think that this work will encourage a number of double blind clinical trials to confirm the effectiveness of the intranasal treatment of the common cold with imiquimod.     

Viral infections and cancer: epidemiological aspects.

Viral infections represent one of the areas in which cancer research has made the greatest advances in the last 20 years. In 1981, only two viruses were known to cause human cancer, i.e., the Epstein-Barr virus (EBV) and the hepatitis B virus (HBV). By 1995, it was estimated that approximately 15% of all cancers occurring world-wide were attributable to viral infections, and the oncogenic role of seven viruses [i.e., EBV, HBV, hepatitis C virus (HCV), human papillomavirus (HPV), human immunodeficiency virus (HIV), human herpesvirus-8 (HHV-8), and human T cell leukemia virus type I (HTLV-I)] has been well-established. In this paper, the epidemiological evidence concerning some of the major aspects of the association between viruses and cancer are summarised.     

Flies as a source of enteric pathogens in a rural village in Thailand

The village of Ban Pong in northeastern Thailand was studied from January through December 1981 to determine the importance of flies as a source of enteric pathogens. The number of flies (predominantly Musca domestica) increased in kitchens and animal pens in the hot dry spring, when the incidence of diarrhea was highest in the village. Enterotoxigenic Escherichia coli, Shigella spp., non-O1 Vibrio cholerae, and Vibrio fluvalis were isolated from fly pools in yards (69%), animal pens (38%), bathrooms (35%), and kitchens (8%). Enterotoxigenic E. coli was isolated from one fly pool in May and from another in June, when the incidence of such infections was highest in the village. Flies often carry and presumably disseminate enteric pathogens in rural Thailand.     

Nocardia cyriacigeorgica is a significant pathogen responsible for nocardiosis in Japan and Thailand

Nocardia cyriacigeorgica is a recently described species. During routine diagnostic testing of 121 clinical isolates, we found that about one fourth of the strains from Japan (19 isolates) and Thailand (8 isolates), which were identified in our laboratories as N. asteroides, in fact belong to N. cyriacigeorgica. To our knowledge, this is the first report of infection due to N. cyriacigeorgica in Japan and Thailand, and the third report of infection anywhere in the world. Although N. cyriacigeorgica is usually differentiated from other Nocardia species by utilization of glucose and gluconate, we found that it can also be differentiated by a characteristic synergistic effect between imipenem (IPM) and tobramycin (TOB).     

Misdirected antibody responses against an N-terminal epitope on human rhinovirus VP1 as explanation for recurrent RV infections

Rhinoviruses (RVs) are the primary cause of upper respiratory tract infections, generally known as the common cold. Moreover, RV infections can trigger severe exacerbations of asthma and chronic obstructive pulmonary disease (COPD). We expressed the 4 major RV capsid proteins, VP1-VP4, in Escherichia coli and used these proteins as well as recombinant and synthetic VP1 fragments to study and map antibody responses in RV-infected humans. VP1, which on infection binds to ICAM 1, was identified as a major target for the memory immune response, residing in the IgG1 subclass and IgA class. Interestingly, this response was mainly directed against an N-terminal 20 mer peptide in VP1, P1a, which becomes exposed on intact RV only when it docks to its receptor ICAM 1. Molecular modeling using the 3-dimensional RV capsid structures revealed that P1a was localized inside the capsid and outside the areas involved in receptor binding or RV neutralization. Our results suggest misdirection of antibody responses against a nonprotective epitope as a mechanism how RV escapes immunity and causes recurrent infections. Based on these findings, it may be possible to design vaccines against RV infections and RV-induced respiratory diseases.     

Flies as a source of enteric pathogens in a rural village in Thailand.

The village of Ban Pong in northeastern Thailand was studied from January through December 1981 to determine the importance of flies as a source of enteric pathogens. The number of flies (predominantly Musca domestica) increased in kitchens and animal pens in the hot dry spring, when the incidence of diarrhea was highest in the village. Enterotoxigenic Escherichia coli, Shigella spp., non-O1 Vibrio cholerae, and Vibrio fluvalis were isolated from fly pools in yards (69%), animal pens (38%), bathrooms (35%), and kitchens (8%). Enterotoxigenic E. coli was isolated from one fly pool in May and from another in June, when the incidence of such infections was highest in the village. Flies often carry and presumably disseminate enteric pathogens in rural Thailand.     

Population-genetic evidence for two species in Anopheles minimus in Thailand

ABSTRACT. Sympatric occurrence of homozygotes for two electro-morphs controlled by a locus for octanol dehydrogenase, and the absence of heterozygotes, at two localities, indicates two isomorphic species within the taxon Anopheles minimus Theobald in Thailand. This view is supported by significant, relative deficiences of heterozygotes at other electromorphic loci. Gene frequency data are reported for seven electro-morphic loci in An.minimus sensu lato from eleven localities: one of the newly recognized species predominated in all but one locality and the second was confined to two localities. This species pair of An.minimus s.l. was clearly distinguished from An.aconitus Donitz, An.pampanai Biittiker & Beales and An.varuna Iyengar, three species closely related to An.minimus s.l. in the series Myzomyia of Anopheles subgenus Cellia.     

Electron microscopy as a diagnostic method in the epidemiological surveillance of poxvirus infections

The materials of work lasting for 11 years and including the study of 3,425 samples collected at different periods after the eradication of smallpox from patients suspected for orthopoxvirus infection indicate high effectiveness of electron microscopy and especially immune electron microscopy as an integral part of diagnostic examination.     

Severe infections caused by Propionibacterium acnes: an underestimated pathogen in late postoperative infections.

Propionibacterium acnes belongs to the cutaneous flora of humans and is rarely considered a pathogen in human diseases. It is a frequent contaminant in blood cultures; however, in some patients it has been identified as the causative agent of life-threatening infections. Within the last years we have observed an abrupt increase in severe P. acnes infections which prompted us to study in detail the clinical and microbiological features, risk factors, and outcomes of these cases. In a retrospective review of microbiological records of 905 Propionibacterium isolates from a five-year period (1990-95), 70 were identified from 20 patients with clinical and microbiological evidence of a P. acnes infection. The clinical syndromes included endocarditis (7 patients), post-craniotomy infections (6 patients), arthritis and spondylodiscitis (4 patients), endophthalmitis (2 patients) and pansinusitis (1 patient). The predominant predisposing conditions were previous surgery preceding the infection from 2 weeks to 4 years and implantation of foreign bodies such as prosthetic heart valves, intraocular lenses and ventriculo-peritoneal shunts. Therapy consisted of intravenous antibiotics in all cases and surgical procedures to remove infected tissue in eighteen patients. The outcome was favorable in sixteen patients (80 percent) who had a complete recovery. These data confirm the pathogenic potential of P. acnes in late post-surgical infections, in particular after implantation of a foreign body, and suggest a combined therapeutic approach with intravenous antibiotics and surgical removal of the infected tissue.     

Escherichia coli infections in newborn puppies--clinical and epidemiological investigations

Epidemiological analyses were performed in five breeding kennels with Escherichia coli infections in newborn pups using pulsed field gel electrophoresis (PFGE). Previous reports demonstrated the high discriminatory power of this method and its usefulness for detecting epidemiologically related isolates. A total of 113 E. coli strains were isolated from vagina, faeces, oral cavity, milk and organs from 19 adult dogs, and 57 diseased or dead pups from 12 litters. Restriction enzyme analyses were performed using XbaI and BlnI digests and the resulting 91 DNA patterns were aligned for comparison. The results showed that a total of 60% of E. coli strains from progeny were also found in vaginal samples of the mothers. Another bacterial source was the faeces found within the kennels. One instance of milk and oral cavity isolates of the mother was found to be identical with strains isolated from the pups. The results indicate that for repeated cases of E. coli infections in neonates, diagnostic procedures of vaginal and faecal swabs from dams result in isolation of the responsible bacteria with high probability and further suggest that preterm treatment could help to control bacterial diseases and losses in pups. In addition, the observation that two canine strains were found to be identical with an E. coli strain isolated from a human case of diarrhoea strongly supports the canine reservoir hypothesis.     

Human papillomavirus infections: new perspectives for prevention and treatment

Human papillomaviruses (HPVs) have been recognized as the main etiologic agent of cervical cancer and other anogenital neoplasms, and a leading cause of death from cancer worldwide. In the last twenty years, extensive research has contributed to document the molecular mechanisms of virus persistence and malignant transformation, confirming a direct role of viral proteins in these processes. A clear understanding of the molecular epidemiology of HPVs and the availability of powerful molecular diagnostic techniques have provided the background for prevention strategies of HPV-related carcinomas. Since these viruses are highly prevalent in the general population, strict screening programs are still necessary. Recently, major breakthroughs have emerged from immunological studies. Indeed, these studies have paved the way for medical treatment of HPV infections and provided the first highly effective preventive vaccines. For these principal reasons, the time has come for a great effort towards the eradication of these important human pathogens. The present review summarizes the main aspects of the virology, molecular epidemiology and molecular biology of HPV infection and highlights the recent perspectives of prevention and treatment of the HPV-related disease.     

Severe Human Influenza Infections in Thailand: Oseltamivir Treatment and Risk Factors for Fatal Outcome

Background

Influenza is often not recognized as an important cause of severe or fatal disease in tropical and subtropical countries in Southeast Asia. The extent to which Oseltamivir treatment may protect against a fatal outcome in severe influenza infections is not known. Thailand''s National Avian Influenza Surveillance (NAIS) system affords a unique opportunity to describe the epidemiology of laboratory-confirmed severe and fatal human influenza infections.

Methodology/Principal Findings

During January 2004 through December 2006, 11,641 notifications to the NAIS were investigated in 73 of 76 Thai provinces. Clinical and demographic data and respiratory swab specimens were collected and tested by PCR for influenza. Using the NAIS database, we identified all patients with laboratory confirmed human influenza (A/H3N2, A/H1N1 and Type B) infection. A retrospective medical record review was conducted on all fatal cases with laboratory confirmed influenza and from a sample of hospitalized cases in 28 provinces. The association of underlying risk factors, Oseltamivir treatment and risk of a fatal outcome were examined. Human influenza infections were identified in 2,075 (18%) cases. Twenty-two (1%) deaths occurred including seven deaths in children less than ten years of age. Thirty-five percent of hospitalized human influenza infections had chest X-ray confirmed pneumonia. Current or former smoking; advanced age, hypertension and underlying cardiovascular, pulmonary or endocrine disease were associated with a fatal outcome from human influenza infection. Treatment with Oseltamivir was statistically associated with survival with a crude OR of .11 (95% CI: 0.04–0.30) and .13 (95% CI: 0.04–0.40) after controlling for age.

Conclusions

Severe and fatal human influenza infections were commonly identified in the NAIS designed to identify avian A/H5N1 cases. Treatment with Oseltamivir is associated with survival in hospitalized human influenza pneumonia patients.     

From within-host interactions to epidemiological competition: a general model for multiple infections

Many hosts are infected by several parasite genotypes at a time. In these co-infected hosts, parasites can interact in various ways thus creating diverse within-host dynamics, making it difficult to predict the expression and the evolution of virulence. Moreover, multiple infections generate a combinatorial diversity of cotransmission routes at the host population level, which complicates the epidemiology and may lead to non-trivial outcomes. We introduce a new model for multiple infections, which allows any number of parasite genotypes to infect hosts and potentially coexist in the population. In our model, parasites affect one another''s within-host growth through density-dependent interactions and by means of public goods and spite. These within-host interactions determine virulence, recovery and transmission rates, which are then integrated in a transmission network. We use analytical solutions and numerical simulations to investigate epidemiological feedbacks in host populations infected by several parasite genotypes. Finally, we discuss general perspectives on multiple infections.