Estimate of Burden and Direct Healthcare Cost of Infectious Waterborne Disease in the United States

Provision of safe drinking water in the United States is a great public health achievement. However, new waterborne disease challenges have emerged (e.g., aging infrastructure, chlorine-tolerant and biofilm-related pathogens, increased recreational water use). Comprehensive estimates of the health burden for all water exposure routes (ingestion, contact, inhalation) and sources (drinking, recreational, environmental) are needed. We estimated total illnesses, emergency department (ED) visits, hospitalizations, deaths, and direct healthcare costs for 17 waterborne infectious diseases. About 7.15 million waterborne illnesses occur annually (95% credible interval [CrI] 3.88 million–12.0 million), results in 601,000 ED visits (95% CrI 364,000–866,000), 118,000 hospitalizations (95% CrI 86,800–150,000), and 6,630 deaths (95% CrI 4,520–8,870) and incurring US $3.33 billion (95% CrI 1.37 billion–8.77 billion) in direct healthcare costs. Otitis externa and norovirus infection were the most common illnesses. Most hospitalizations and deaths were caused by biofilm-associated pathogens (nontuberculous mycobacteria, Pseudomonas, Legionella), costing US $2.39 billion annually.     

The prevalence of gestational diabetes mellitus in Bangladesh: a systematic review and meta-analysis

International Journal of Diabetes in Developing Countries - Currently, gestational diabetes mellitus (GDM) is a major public health concern with a higher risk of adverse pregnancy outcomes for both...     

The prevalence of traumatic dental injuries to permanent anterior teeth and its relation with predisposing risk factors among 8-13 years school children of Vadodara city: An epidemiological study

Background and objective: dental trauma is an irreversible pathology that after occurrence is characterized by life-long debilitating effects. The objectives of this study were to measure the prevalence of anterior teeth fracture and their association with predisposing factors such as lip coverage, molar relationship, overjet, and variables such as age, sex, cause, and place of trauma. Materials and Methods: an epidemiological cross-sectional study was carried out among 3708 school children aged 8-13 years in the Vadodara city. All children completed a questionnaire related to history of trauma to their anterior teeth after which they were examined for lip competence, Angle's molar relationship amount of overjet and nature of trauma sustained. The results were statistically analyzed using the prevalence test, Chi-square test, and Mantel-Haenszel Common Odds Ratio. Results: the prevalence of traumatic injuries was 8.79% and the ratio of boys: girl's was 1.28:1. Inadequate lip coverage group sustained about five times more injuries than the adequate lip coverage group (P = 0.000, OR= 5.407). The maximum traumatic injuries were seen in children having Angle Class II Div 1 molar relationship and/or overjet greater than 5.5 mm and was statistically significant (P<0.05). Maximum number of injuries occurred at 9 years of age. The most predominant injuries were enamel fractures, the most common place for occurrence was home and fall against object, the most frequent cause. Conclusion: the prevalence of dental injuries in the Vadodara city is high and it has a great potential to be considered as an emerging public health problem.     

血浆总同型半胱氨酸测定在智力低下等神经精神异常病因调查中的应用

目的调查原因不明的神经精神异常及甲基丙二酸尿症患儿中同型半胱氨酸血症的发生情况,探讨荧光偏振免疫测定法进行血浆或血清总同型半胱氨酸测定的应用价值。方法对2000年1月至2007年12月因原因不明的智力低下、运动障碍、癫疒间、头痛等多种神经系统异常患儿799例,甲基丙二酸尿症126例患儿,采用荧光偏振免疫测定法检测血液总同型半胱氨酸,气相色谱质谱联用分析测定尿液有机酸,液相串联质谱法进行血液氨基酸、酯酰肉碱谱分析。结果925例高危患儿中共发现同型半胱氨酸血症128例（13.84%）。799例原因不明的神经系统疾病患儿中同型半胱氨酸血症27例（3.38%）,血液丙酰肉碱及游离氨基酸浓度正常。126例甲基丙二酸尿症患儿中合并同型半胱氨酸血症101例（80.16%）,血液丙酰肉碱浓度增高。结论甲基丙二酸尿症合并同型半胱氨酸血症是甲基丙二酸尿症的主要临床表型,为鉴别诊断、正确治疗,应及早进行血液总同型半胱氨酸测定。应用荧光偏振免疫测定法检测血清/血浆总同型半胱氨酸,是同型半胱氨酸血症高危筛查的可靠方法。     

A Novel Iminosugar UV-12 with Activity against the Diverse Viruses Influenza and Dengue (Novel Iminosugar Antiviral for Influenza and Dengue)

Iminosugars are capable of targeting the life cycles of multiple viruses by blocking host endoplasmic reticulum α-glucosidase enzymes that are required for competent replication of a variety of enveloped, glycosylated viruses. Iminosugars as a class are approved for use in humans with diseases such as diabetes and Gaucher’s disease, providing evidence for safety of this class of compounds. The in vitro antiviral activity of iminosugars has been described in several publications with a subset of these demonstrating in vivo activity against flaviviruses, herpesviruses, retroviruses and filoviruses. Although there is compelling non-clinical in vivo evidence of antiviral efficacy, the efficacy of iminosugars as antivirals has yet to be demonstrated in humans. In the current study, we report a novel iminosugar, UV-12, which has efficacy against dengue and influenza in mouse models. UV-12 exhibits drug-like properties including oral bioavailability and good safety profile in mice and guinea pigs. UV-12 is an example of an iminosugar with activity against multiple virus families that should be investigated in further safety and efficacy studies and demonstrates potential value of this drug class as antiviral therapeutics.     

Cross‐sectional survey of the disaster preparedness of nurses across the Asia–Pacific region

Healthcare workers who have received disaster preparedness education are more likely to report a greater understanding of disaster preparedness. However, research indicates that current nursing curricula do not adequately prepare nurses to respond to disasters. This is the first study to assess Asia–Pacific nurses' perceptions about their level of disaster knowledge, skills, and preparedness. A cross‐sectional survey was conducted with 757 hospital and community nurses in seven Asia–Pacific countries. Data were collected using the modified Disaster Preparedness Evaluation Tool. Participants were found to have overall low‐to‐moderate levels of disaster knowledge, skills and preparedness, wherein important gaps were identified. A majority of the variance in disaster preparedness scores was located at the level of the individual respondent, not linked to countries or institutions. Multilevel random effects modelling identified disaster experience and education as significant factors of positive perceptions of disaster knowledge, skills, and management. The first step toward disaster preparedness is to ensure frontline health workers are able to respond effectively to disaster events. The outcomes of this study have important policy and education implications.     

From the Cover: PNAS Plus: Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8+ T cells

The role of CD8⁺ T cells in dengue virus infection and subsequent disease manifestations is not fully understood. According to the original antigenic sin theory, skewing of T-cell responses induced by primary infection with one serotype causes less effective response upon secondary infection with a different serotype, predisposing individuals to severe disease. A comprehensive analysis of CD8⁺ responses in the general population from the Sri Lankan hyperendemic area, involving the measurement of ex vivo IFNγ responses associated with more than 400 epitopes, challenges the original antigenic sin theory. Although skewing of responses toward primary infecting viruses was detected, this was not associated with impairment of responses either qualitatively or quantitatively. Furthermore, we demonstrate higher magnitude and more polyfunctional responses for HLA alleles associated with decreased susceptibility to severe disease, suggesting that a vigorous response by multifunctional CD8⁺ T cells is associated with protection from dengue virus disease.Dengue virus (DENV) is the etiologic agent of dengue fever (DF), the most significant mosquito-borne viral disease in humans. Disease can be caused by any of the four DENV serotypes (DENV1 to -4), which share 67–75% sequence homology with one another (1). DENV transmission occurs in more than 100 countries and is an increasing public health problem in tropical and subtropical regions (2). Demographic changes, urbanization, and international travel contribute to the expansion of geographical areas where transmission occurs, and all four DENV serotypes are now circulating in Asia, Africa, and the Americas (3, 4). Up to 100 million DENV infections occur every year (5), and severity can range from asymptomatic to an acute self-limiting febrile illness (DF). In a small proportion of patients, the disease can exacerbate and progress to dengue hemorrhagic fever (DHF) and/or dengue shock syndrome (DSS), characterized by severe vascular leakage, thrombocytopenia, and hemorrhagic manifestations (4).Although natural infection by any of the four DENV serotypes (primary infection) produces a lasting protective immunity against reinfection by the same serotype, it does not protect against infections with other serotypes (secondary infections) (6, 7). Epidemiologic studies have shown that the majority of individuals that develop DHF/DSS had been previously infected with a different serotype (8). Consequently, the development of DENV vaccines has been hampered by the potential risk of vaccine-related adverse events and the requirement to induce long-lasting protective immune responses against all four DENV serotypes simultaneously (9). The cause for the increased frequency of DHF following secondary infections has not been fully elucidated. One hypothesis is that serotype cross-reactive antibodies exacerbate disease by increasing infection of cells bearing Fcγ receptors, resulting in higher viral loads and more severe disease via this antibody-dependent enhancement (ADE) of infection (10, 11). Indeed, nonhuman primate and murine models have demonstrated that antibodies can lead to enhancement of DENV infection and disease in vivo (12–15).Another hypothesis postulates that T cells raised against the first infecting serotype dominate during a secondary heterologous infection in a phenomenon termed “original antigenic sin” (16, 17). This term was first applied to the humoral response to influenza epidemics (18) but has also been observed in CD8⁺ T-cell responses against lymphocytic choriomeningitis virus (19). This hypothesis postulates that, during secondary infection, expansion of preexisting lower avidity cross-reactive memory T cells dominate the responses over that of naïve T cells that are of higher avidity for the new DENV serotype. This expansion of low avidity T cells results in less efficient elimination of DENV-infected cells.A role for T cells in control of DENV infection is suggested by several studies that implicate HLA associations as a genetic component to variable susceptibility to DENV disease (20–26). However, it has not been addressed whether these associations might indicate a positive or detrimental role for T-cell responses. One major obstacle to the elucidation of the function of T cells is the lack of a comprehensive characterization of HLA-restricted DENV responses in the context of natural infection.Herein, we present a comprehensive analysis of functional T-cell memory against DENV and are able to correlate this with HLA alleles expressed in the very same donors. Collectively, the data suggest an HLA-linked protective role of CD8⁺ T-cell responses and do not support a causative role for CD8⁺ T cells in the induction of severe disease following secondary heterologous infection.     

Study of effusion cytology in patients with simultaneous malignancy and ascites

Objective: To evaluate sensitivity of effusion cytology in detecting malignancy Materials and methods: Effusion cytology was studied from 37 malignancy associated and 28 non malignancy associated ascitic fluid samples. Results: Out of 65 cases, 44 (67.7%) effusions were reported negative, 15 (23.1%) were positive and 6 (9.2%) were suspicious for malignancy. Thus total 21 effusions (32.3%) were tumour cell positive. All 21 (100%) were true positive, none (0%) was false positive, 28 (63.6%) were true negative and 16 (36.4%) were false negative. Thus ascitic fluid cytology had sensitivity of 56.7% and specificity of 100%. Predictive value of positive test and negative test was 100% and 63.6% respectively. Stomach was the most common primary site of malignancy associated with ascites (11 /37 i.e. 29.7%) where as adenocarcinoma was the most common type of malignancy (11/15 i.e.73.3%) in ascitic fluid cytology. Conclusion: Ascitic fluid cytology is a simple and useful procedure with sensitivity of 56.7% and should be routinely requested. Key words: Ascitic fluid, Effusion cytology.     

Polymorphism of glutathione S-transferase omega gene and risk of cancer

Polymorphic glutathione S-transferase (GST) genes causing variations in enzyme activity may influence individual susceptibility to cancer. Though polymorphisms have been reported in GSTO1 and GSTO2, their predisposition to cancer risk has not yet been explored. In this case control study, 28 cases of hepatocellular carcinoma, 30 cases of cholangiocarcinoma, 31 cases of colorectal cancer, 30 cases of breast cancer and 98 controls were compared for frequencies of GSTO1 and GSTO2 genotypes. The statistical analysis provided the support for the difference in genotypic distribution for GSTO1*A140D between hepatocellular carcinoma (OR 23.83, CI 95%: 5.07-127), cholangiocarcinoma (OR 8.5, CI 95%: 2.07-37.85), breast cancer (OR 3.71, CI 95%: 1.09-13.02) and control. With regards to GSTO2*N140D polymorphism, there was no difference in genotypic distribution between all the types of cancer and control. The study suggests that GSTO1*A140D polymorphism could play an important role as a risk factor for the development of hepatocellular carcinoma, cholangiocarcinoma and breast cancer.