2014-2016年南充市儿童手足口病重症流行病学调查及危险因素分析

摘要 目的：了解南充市儿童重症手足口病流行病学特征及其相关危险因素,为降低儿童重症手足口病发病率提供依据。方法：对中国"疾病监测信息报告管理系统"中确诊的南充市（顺庆区、高坪区、嘉陵区、阆中市）2014-2016年儿童手足口病的病例信息进行研究,分析该市儿童手足口病疫情、时间分布、地区分布和人群分布特征,并应用单因素和多因素Logistic回归分析儿童重症手足口病危险因素。结果：2014-2016年顺庆区、高坪区、嘉陵区、阆中市共报告儿童手足口病8068例,其中重症病例426例,占5.28%。全年均有手足口病发生,4~7月为手足口病发病高峰期,2014年峰值明显高于2015年、2016年,重症手足口病时间分布和发病高峰期与以上相同。顺庆区、高坪区、嘉陵区、阆中市均有手足口病发生,阆中市重症病例比例均高于其他辖区,差异有统计学意义（P<0.05）。男性患儿重症病例构成比较高,不同性别患儿重症病例构成比比较差异有统计学意义（P<0.05）;重症病例主要集中在1~3岁儿童,不同年龄段重症病例构成比比较差异有统计学意义（P<0.05）,重症病例主要分布在散居儿童和农村儿童,不同生活方式、不同家庭住址重症病例构成比比较差异有统计学意义（P<0.05）;重症病例主要分布在3~6天时间间隔的就诊患儿,不同就诊时间间隔重症病例构成比比较差异有统计学意义（P<0.05）。多因素Logistic分析显示：年龄为1-3岁、散居、家庭住址为农村是重症手足口病的危险因素（P<0.05）。结论：年龄为1-3岁、散居、家庭住址为农村是重症手足口病的危险因素,应在流动人口集中、生活条件较差的地区开展手足口病的宣传教育,提高人们对手足口病防治的认知,对于1-3岁儿童应作为疾病重点防控对象,提高家长疾病防控意识,以降低重症手足口病的发病率。     

Disease characteristics and serological responses in patients with differing severity of COVID-19 infection: A longitudinal cohort study in Dhaka,Bangladesh

BackgroundCOVID-19 caused by SARS-CoV-2 ranges from asymptomatic to severe disease and can cause fatal and devastating outcome in many cases. In this study, we have compared the clinical, biochemical and immunological parameters across the different disease spectrum of COVID-19 in Bangladeshi patients.Methodology/Principal findingsThis longitudinal study was conducted in two COVID-19 hospitals and also around the community in Dhaka city in Bangladesh between November 2020 to March 2021. A total of 100 patients with COVID-19 infection were enrolled and classified into asymptomatic, mild, moderate and severe cases (n = 25/group). In addition, thirty age and sex matched healthy participants were enrolled and 21 were analyzed as controls based on exclusion criteria. After enrollment (study day1), follow-up visits were conducted on day 7, 14 and 28 for the cases.Older age, male gender and co-morbid conditions were the risk factors for severe COVID-19 disease. Those with moderate and severe cases of infection had low lymphocyte counts, high neutrophil counts along with a higher neutrophil-lymphocyte ratio (NLR) at enrollment; this decreased to normal range within 42 days after the onset of symptom. At enrollment, D-dimer, CRP and ferritin levels were elevated among moderate and severe cases. The mild, moderate, and severe cases were seropositive for IgG antibody by day 14 after enrollment. Moderate and severe cases showed significantly higher IgM and IgG levels of antibodies to SARS-CoV-2 compared to mild and asymptomatic cases.Conclusion/SignificanceWe report on the clinical, biochemical, and hematological parameters associated with the different severity of COVID-19 infection. We also show different profile of antibody response against SARS-CoV-2 in relation to disease severity, especially in those with moderate and severe disease manifestations compared to the mild and asymptomatic infection.     

Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

Pandemic influenza viruses often cause severe disease in middle-aged adults without preexisting comorbidities. The mechanism of illness associated with severe disease in this age group is not well understood. Here we find preexisting serum antibodies that cross-react with, but do not protect against, 2009 H1N1 influenza virus in middle-aged adults. Nonprotective antibody is associated with immune complex-mediated disease after infection. We detected high titers of serum antibody of low avidity for H1-2009 antigen, and low-avidity pulmonary immune complexes against the same protein, in severely ill individuals. Moreover, C4d deposition--a marker of complement activation mediated by immune complexes--was present in lung sections of fatal cases. Archived lung sections from middle-aged adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a previously unknown biological mechanism for the unusual age distribution of severe cases during influenza pandemics.     

Analysis of 5' nontranslated region of hepatitis A viral RNA genotype I from South Korea: comparison with disease severities

The aim of the study was to analyze genotype I hepatitis A virus (HAV) 5' nontranslated region (NTR) sequences from a recent outbreak in South Korea and compare them with reported sequences from Japan. We collected a total of 54 acute hepatitis A patients' sera from HAV genotype I [27 severe disease (prothrombin time INR ≥ 1.50) and 27 mild hepatitis (prothrombin time INR <1.00)], performed nested RT-PCR of 5' NTR of HAV directly sequenced from PCR products (～ 300 bp), and compared them with each other. We could detect HAV 5'NTR sequences in 19 of the 54 (35.1%) cases [12 of 27 severe cases (44.4%) and 7 of 27 self-limited cases (25.9%)], all of which were subgenotype IA. Sequence analysis revealed that sequences of severe disease had 93.6%-99.0% homology and of self-limited disease 94.3%-98.6% homology, compared to subgenotype IA HAV GBM wild-type IA sequence. In this study, confirmation of the 5'NTR sequence differences between severe disease and mild disease was not carried out. Comparison with Japanese HAV A10 revealed (222)C to G or T substitution in 8/12 cases of severe disease and (222)C to G or T and (392)G to A substitutions in 5/7 and 4/7 cases of mild disease, respectively, although the nucleotide sequences in this study showed high homology (93.6%-100%). In conclusion, HAV 5'NTR subgenotype IA from Korea had relatively high homology to Japanese sequences previously reported from Japan, and this region would be considered one of the antiviral targets. Further studies will be needed.     

高脂血症性胰腺炎26例临床治疗分析

目的:分析26例高脂血症性胰腺炎的治疗及预后,探讨高脂血症性胰腺炎的治疗特点。方法:总结我科03．8-06．10间收治的高脂血症性胰腺炎病人26例的治疗及预后。结果:在高脂血症性胰腺炎26例,其中重症病例11例,重症病例中死亡二例,手术三例,合并糖尿病4例、合并高血压、冠心病5例,在所有高脂血症性胰腺炎中除重症中2例死亡外,其余根据胰腺炎的严重程度不同采用相应的治疗办法而全部治愈。结论:高脂血症性胰腺炎的发病率相对较高,其并发病多、死亡率高,治疗以降血脂为主的多方位的综合治疗,血液净化是重症高脂血症性胰腺炎早期治疗一种较有用的方式。     

TGF-beta 1 variants in chronic beryllium disease and sarcoidosis

Evidence suggests a genetic predisposition to chronic beryllium disease (CBD) and sarcoidosis, which are clinically and pathologically similar granulomatous lung diseases. TGF-beta1, a cytokine involved in mediating the fibrotic/Th1 response, has several genetic variants which might predispose individuals to these lung diseases. We examined whether certain TGF-beta1 variants and haplotypes are found at higher rates in CBD and sarcoidosis cases compared with controls and are associated with disease severity indicators for both diseases. Using DNA from sarcoidosis cases/controls from A Case Control Etiologic Study of Sarcoidosis Group (ACCESS) and CBD cases/controls, TGF-beta1 variants were analyzed by sequence-specific primer PCR. No significant differences were found between cases and controls for either disease in the TGF-beta1 variants or haplotypes. The -509C and codon 10T were significantly associated with disease severity indicators in both CBD and sarcoidosis. Haplotypes that included the -509C and codon 10T were also associated with more severe disease, whereas one or more copies of the haplotype containing the -509T and codon 10C was protective against severe disease for both sarcoidosis and CBD. These studies suggest that the -509C and codon 10T, implicated in lower levels of TGF-beta1 protein production, are shared susceptibility factors associated with more severe granulomatous disease in sarcoidosis and CBD. This association may be due to lack of down-regulation by TGF-beta1, although future studies will be needed to correlate TGF-beta1 protein levels with known TGF-beta1 genotypes and assess whether there is a shared mechanisms for TGF-beta1 in these two granulomatous diseases.     

Mouse models of SMA: tools for disease characterization and therapeutic development

Mouse models of human disease are an important tool for studying disease mechanism and manifestation in a way that is physiologically relevant. Spinal muscular atrophy (SMA) is a neurodegenerative disease that is caused by deletion or mutation of the survival motor neuron gene (SMN1). The SMA disease is present in a spectrum of disease severities ranging from infant mortality, in the most severe cases, to minor motor impairment, in the mildest cases. The variability of disease severity inversely correlates with the copy number, and thus expression of a second, partially functional survival motor neuron gene, SMN2. Correspondingly, a plethora of mouse models has been developed to mimic these different types of SMA. These models express a range of SMN protein levels and extensively cover the severe and mild types of SMA, with neurological and physiological manifestation of disease supporting the relevance of these models. The SMA models provide a strong background for studying SMA and have already shown to be useful in pre-clinical therapeutic studies. The purpose of this review is to succinctly summarize the genetic and disease characteristic of the SMA mouse models and to highlight their use for therapeutic testing.     

Low serum calcium: a new,important indicator of COVID-19 patients from mild/moderate to severe/critical

Background: Coronavirus disease 2019 (COVID-19) virus is still spreading, finding out the initial hits of viral infection is important to minimize the mild/moderate population, prevent disease aggravation and organs dysfunction.Objective: We investigated COVID-19 patients with different serum calcium levels.Design: We checked the serum calcium level of the patients based on days after symptom onset as well as the severity of COVID-19. We also checked multiorgan injuries and immune cytokines level in their blood.Results: Both mild/moderate and severe critical cases we observed showed low calcium level in the early stage of viral infection, while the severe/critical cases showed significant lower calcium level than mild/moderate cases in the early stage. We also found that low calcium level related to severe/critical multiorgan injuries especially in the mild/moderate population. Proinflammatory cytokine IL-6 also correlated to calcium change in both mild/moderate and severe/critical cases.Conclusions: Our finding indicates that calcium balance is a primal hit of COVID-19 and a biomarker of clinical severity at the beginning of symptom onset. Calcium is closely associated with virus-associated multiple organ injuries and the increase in inflammatory cytokines. Our results provide a new, important indicator of COVID-19 patients from mild/moderate to severe/critical: serum calcium.     

TERRAMYCIN IN URINARY TRACT INFECTIONS

Terramycin® is an effective agent in the control of urinary tract infections with organisms of the enteric group.The drug is tolerated by mouth and no serious side-reactions occur. In cases in which there is no organic or obstructive disease, the response to Terramycin as a urinary antiseptic is prompt and effective. In several cases in which there was severe organic and obstructive disease and the organism was highly resistant, the course of the disease was not altered by giving Terramycin.     

A 50-year perspective of a family with chromosome-14-linked Alzheimer’s disease

A Swedish family with two generations suffering from presenile dementia with an unusually severe Alzheimer encephalopathy was first reported in 1946. The hypothesis that the disease was inherited through a dominant gene is strongly supported by the follow-up 50years later of three additional generations and molecular genetic findings of a novel presenilin-1 gene mutation in the family. The pedigree contains six cases with well-documented dementia in four consecutive generations. The Alzheimer encephalopathy was unusually severe in the three cases studied post-mortem, with a pronounced involvement of the central grey structures, such as the claustrum, the nuclei around the third ventricle, the central thalamic nuclei and the brain stem. There were no vascular lesions and little amyloid angiopathy. All six affected cases showed the typical temporoparietal symptom pattern and other core symptoms of Alzheimer’s disease, such as logoclonia, myoclonic twitchings and major motor seizures. Other predominant features were psychomotor slowness, increased muscular tension, a stiff stooped gait and a rapid loss of weight. The symptom pattern is convincingly explained by the consistent and severe involvement of cortical and central grey structures and is probably linked to the presenilin-1 gene mutation. Received: 25 November 1997 / Accepted 4 December 1997     

The genotype-phenotype correlation in Pompe disease

Pompe disease is an autosomal recessive lysosomal glycogen storage disorder that is caused by acid α-glucosidase (GAA) deficiency and is due to pathogenic sequence variations in the corresponding GAA gene. The correlation between genotypes and phenotypes is strict, in that patients with the most severe phenotype, classic infantile Pompe disease, have two pathogenic mutations, one in each GAA allele, that prevent the formation of GAA or totally obliterates its function. All patients with less progressive phenotypes have at least one sequence variation that allows normal or low level synthesis of GAA leading to the formation of analytically measurable, low level GAA activity in most cases. There is an overall trend of finding higher GAA enzyme levels in patients with onset of symptoms in adulthood when compared to patients who show clinical manifestations in early childhood, aged 0-5 years, with a rapidly progressive course, but who lack the severe characteristics of classic infantile Pompe disease. However, several cases have been reported of adult-onset disease with very low GAA activity, which in all those cases corresponds with the GAA genotype. The clinical diversity observed within a large group of patients with functionally the same GAA genotype and the same c.-32-13C?>?T haplotype demonstrates that modifying factors can have a substantial effect on the clinical course of Pompe disease, disturbing the GAA genotype-phenotype correlation. The present day challenge is to identify these factors and explore them as therapeutic targets.     

Use of Cumulative Incidence of Novel Influenza A/H1N1 in Foreign Travelers to Estimate Lower Bounds on Cumulative Incidence in Mexico

Background

An accurate estimate of the total number of cases and severity of illness of an emerging infectious disease is required both to define the burden of the epidemic and to determine the severity of disease. When a novel pathogen first appears, affected individuals with severe symptoms are more likely to be diagnosed. Accordingly, the total number of cases will be underestimated and disease severity overestimated. This problem is manifest in the current epidemic of novel influenza A/H1N1.

Methods and Results

We used a simple approach to leverage measures of incident influenza A/H1N1 among a relatively small and well observed group of US, UK, Spanish and Canadian travelers who had visited Mexico to estimate the incidence among a much larger and less well surveyed population of Mexican residents. We estimate that a minimum of 113,000 to 375,000 cases of novel influenza A/H1N1 have occurred in Mexicans during the month of April, 2009. Such an estimate serves as a lower bound because it does not account for underreporting of cases in travelers or for nonrandom mixing between Mexican residents and visitors, which together could increase the estimates by more than an order of magnitude.

Conclusions

We find that the number of cases in Mexican residents may exceed the number of confirmed cases by two to three orders of magnitude. While the extent of disease spread is greater than previously appreciated, our estimate suggests that severe disease is uncommon since the total number of cases is likely to be much larger than those of confirmed cases.     

The Impact of Cardiac Diseases during Pregnancy on Severe Maternal Morbidity and Mortality in Brazil

Background

To evaluate maternal heart disease as a cause or complicating factor for severe morbidity in the setting of the Brazilian Network for Surveillance of Severe Maternal Morbidity.

Methods and Findings

Secondary data analysis of this multicenter cross-sectional study was implemented in 27 referral obstetric units in Brazil. From July 2009 to June 2010, a prospective surveillance was conducted among all delivery hospitalizations to identify cases of severe maternal morbidity (SMM), including Potentially Life-Threatening Conditions (PLTC) and Maternal Near Miss (MNM), using the new criteria established by the WHO. The variables studied included: sociodemographic characteristics, clinical and obstetric history of the women; perinatal outcome and the occurrence of maternal outcomes (PLTC, MNM, MD) between groups of cardiac and non-cardiac patients. Only heart conditions with hemodynamic impact characterizing severity of maternal morbidity were considered. 9555 women were included in the Network with severe pregnancy-related complications: 770 maternal near miss cases and 140 maternal death cases. A total of 293 (3.6%) cases were related to heart disease and the condition was known before pregnancy in 82.6% of cases. Maternal near miss occurred in 15% of cardiac disease patients (most due to clinical-surgical causes, p<0.001) and 7.7% of non-cardiac patients (hemorrhagic and hypertensive causes, p<0.001). Maternal death occurred in 4.8% of cardiac patients and in 1.2% of non-cardiac patients, respectively.

Conclusions

In this study, heart disease was significantly associated with a higher occurrence of severe maternal outcomes, including maternal death and maternal near miss, among women presenting with any severe maternal morbidity.     

Cytokine Response Signatures in Disease Progression and Development of Severe Clinical Outcomes for Leptospirosis

Background

The role of the immune response in influencing leptospirosis clinical outcomes is not yet well understood. We hypothesized that acute-phase serum cytokine responses may play a role in disease progression, risk for death, and severe pulmonary hemorrhage syndrome (SPHS).

Methodology/Principal Findings

We performed a case-control study design to compare cytokine profiles in patients with mild and severe forms of leptospirosis. Among patients hospitalized with severe disease, we compared those with fatal and nonfatal outcomes. During active outpatient and hospital-based surveillance we prospectively enrolled 172 patients, 23 with mild disease (outpatient) and 149 with severe leptospirosis (hospitalized). Circulating concentrations of pro- and anti-inflammatory cytokines at the time of patient presentation were measured using a multiplex bead array assay. Concentrations of IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, and TNF-α were significantly higher (P<0.05) in severe disease compared to mild disease. Among severe patients, levels of IL-6 (P<0.001), IL-8 (P = 0.0049) and IL-10 (P<0.001), were higher in fatal compared to non-fatal cases. High levels of IL-6 and IL-10 were independently associated (P<0.05) with case fatality after adjustment for age and days of symptoms. IL-6 levels were higher (P = 0.0519) among fatal cases who developed SPHS than among who did not.

Conclusion/Significance

This study shows that severe cases of leptospirosis are differentiated from mild disease by a “cytokine storm” process, and that IL-6 and IL-10 may play an immunopathogenic role in the development of life-threatening outcomes in human leptospirosis.     

Mephenesin as a relaxing agent in the treatment of tetanus; clinical experience in 12 cases

Maintenance of a patent airway in cases of tetanus is best accomplished by means of tracheotomy performed early in the course of the disease. This eliminates the possibility of upper respiratory obstruction and facilitates the elimination of irritating and obstructing secretions from the lower respiratory passages. In many cases the amount of sedation required is decidedly reduced following tracheotomy. The combination of phenobarbital and Tolserol(R) is very satisfactory in controlling the muscular rigidity and spasm in cases of moderately severe tetanus. In severe cases, response is not always satisfactory. Severe respiratory depression was observed in only one case in which phenobarbital and Tolserol(R) were used.     

Is antiviral therapy indicated in patients with rheumatological diseases?]

There is recently being observed increase of the specific weight of the opportunistic bacterial-and-viral infections, the initial onset or reactivation of which are associated with the immunity suppression, e.g. due to immunosuppressive therapy. Viral infection in cases with rheumatic diseases often leads to severe process of the main disease and development of serious complications, such as hepatitis, nephritis, pneumonia and others. This is especially actual at the early stages of the disease in cases with viral infection in the anamnesis, since in such cases it activates the main disease, that of course raises the question of the use of antiviral agents in the complex therapy.     

Human babesiosis: an emerging tick-borne disease

Human babesiosis is an important emerging tick-borne disease. Babesia divergens, a parasite of cattle, has been implicated as the most common agent of human babesiosis in Europe, causing severe disease in splenectomized individuals. In the US, Babesia microti, a babesial parasite of small mammals, has been the cause of over 300 cases of human babesiosis since 1969, resulting in mild to severe disease, even in non-splenectomised patients. Changing ecology has contributed greatly to the increase and expansion of human babesiosis in the US. A relatively recently described babesial parasite, the WA1-type, has been shown to be the causative agent in seven human cases in the western US. This parasite is closely related to babesial parasites isolated from large wild ungulates in California. Like B. microti, WA1-type parasites cause mild to severe disease and the immunopathogenesis of these parasites is distinctly different from each other in experimental infections of hamsters and mice. A B. divergens-like parasite was also identified as the cause of a fatal human babesiosis case in Missouri. Isolated cases of human babesisosis have been described in Africa and Mexico, but the causative parasites were not well characterized. Standard diagnostic techniques for human infection, such as examination of Giemsa-stained thin blood smears and serology, have been complemented with molecular techniques, such as PCR. Current treatment for babesiosis is focused on a regimen of clindamycin and quinine, although new drugs have shown promise. Prevention of infection relies on self-monitoring for the presence of ticks and, in some locations, targeted application of pesticides to decrease tick abundance. Identification of human infection with Babesia spp. will probably increase as physicians and the public become more aware of the disease, as people live and recreate in rural tick-infested areas, and as the numbers of immunocompromised individuals increase.     

Interleukin-6 is a potential biomarker for severe pandemic H1N1 influenza A infection

Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data.     

Inflammatory bowel disease in the West Indies.

Inflammatory bowel disease is generally assumed to be rare among negroes and Indians. Over 10 years 34 cases of ulcerative colitis and 14 cases of Crohn''s disease were seen in one medical and one surgical unit in Port-of-Spain, Trinidad. Twenty-six patients were Negroes, 18 were Indians, three were of mixed race, and one was Caucasian. In many of these patients the disease was extensive and several of those with Crohn''s disease suffered severe complications. The assumption that inflammatory bowel disease is rare among West Indians of African and Indian origin therefore seems to be wrong.     

Interferon in patients with hemorrhagic fever with renal syndrome

The in vitro production of alpha- and gamma-interferon (IF) by peripheral blood lymphocytes (PBL) and the concentration of serum IF in 50 patients having hemorrhagic fever with renal syndrome (HFRS), as well as the possibility of the formation of spontaneous IF by PBL and the influence of the patient blood plasma on alpha-IF genesis, was studied. The development of HFRS was accompanied by a rise in the level of serum IF with different speed, depending on the severity of the disease with simultaneous suppression of the lymphocytes capacity for alpha- and especially gamma-IF production. In cases of moderate and severe forms of the disease no restoration of the IF system occurred by the moment of discharge from the hospital. In a few patients spontaneous IF in low titers was determined. In cases of the moderate form of the disease in the oligoanuretic period and the severe form of the disease in the oligoanuretic and polyuretic periods the patients' blood plasma essentially suppressed the production of alpha-IF by PBL.