Campylobacter Enteritis on Hopi and Navajo Indian Reservations—Clinical and Epidemiologic Features

From June 22 through September 30, 1981, stool specimens from 522 Hopi and Navajo outpatients were cultured because of diarrheal illnesses at the Keams Canyon Indian Health Service Hospital, Arizona. Campylobacter jejuni was isolated from the specimens of 26 (5%) of the patients. This pathogen was found as frequently as Shigella in patients younger than 2 years or older than 20 years, but was significantly less common in the 2 to 20-year age group (P<.000001). Campylobacter enteritis was indistinguishable clinically from shigellosis in adult patients, but in children younger than 5 years, a rectal temperature higher than 38°C (100.5°F) was significantly more common with Shigella than with Campylobacter infection (P=.003). In a field study of 20 families, we found that households with a case of Campylobacter enteritis were more likely than age- and community-matched controls to own farm animals (P=.05), but were not more likely to own household pets. C jejuni is less common than Shigella as a cause of summer seasonal diarrhea and dysentery among the Hopi and Navajos; the striking differences in the age-specific rates of these two infections suggest different routes of transmission.     

Infection Status of Hospitalized Diarrheal Patients with Gastrointestinal Protozoa, Bacteria, and Viruses in the Republic of Korea

To understand protozoan, viral, and bacterial infections in diarrheal patients, we analyzed positivity and mixed-infection status with 3 protozoans, 4 viruses, and 10 bacteria in hospitalized diarrheal patients during 2004-2006 in the Republic of Korea. A total of 76,652 stool samples were collected from 96 hospitals across the nation. The positivity for protozoa, viruses, and bacteria was 129, 1,759, and 1,797 per 10,000 persons, respectively. Especially, Cryptosporidium parvum was highly mixed-infected with rotavirus among pediatric diarrheal patients (29.5 per 100 C. parvum positive cases), and Entamoeba histolytica was mixed-infected with Clostridium perfringens (10.3 per 100 E. histolytica positive cases) in protozoan-diarrheal patients. Those infected with rotavirus and C. perfringens constituted relatively high proportions among mixed infection cases from January to April. The positivity for rotavirus among viral infection for those aged ≤ 5 years was significantly higher, while C. perfringens among bacterial infection was higher for ≥ 50 years. The information for association of viral and bacterial infections with enteropathogenic protozoa in diarrheal patients may contribute to improvement of care for diarrhea as well as development of control strategies for diarrheal diseases in Korea.     

Response to antibiotics of Proteus strains isolated from different types of clinical material

The data on the study of the antibiotic response to 42 Proteus strains isolated from different sources in the hospitals of Kharkov are presented. The isolates belonged to P. mirabilis and P. vulgaris. Many strains were resistant to gentamicin, ampicillin and carbenicillin irrespective of the isolation source. 58.0 and 90.3 per cent of the strains isolated from patients with intestinal infections, 66.6 and 100 per cent of the strains isolated from patients with otitis, 33.3 and 66.6 per cent of the strains isolated from patients with bronchopulmonary affections and 100 and 100 per cent of the strains isolated from patients with urological diseases were resistant to gentamicin and carbenicillin, respectively. As for ampicillin, the respective figures were 74.2, 66.6, 66.6 and 100 per cent. All the strains of P. vulgaris isolated from patients with otitis, urological diseases and bronchopulmonary affections were resistant to ampicillin. The MIC of carbenicillin for all the strains except 4 indole-positive strains of P. vulgaris isolated from the faeces and bronchial excreta was much higher than the borderline values.     

Resistance of Shigella to antibiotics

Antibiotic sensitivity of 104 Shigella clinical strains and 104 Escherichia coli strains isolated from patients with acute dysentery not treated with antibiotics in 1986-1987 was studied. It was shown that 100 per cent of the dysentery pathogens and colon bacilli were antibiotic resistant. Strains resistant simultaneously to chloramphenicol, ampicillin, streptomycin, tetracycline, monomycin and kanamycin were the most frequent among the dysentery pathogens. Colon bacilli and dysentery pathogens isolated from the same patient had specific sets of antibiotic resistance markers. Pathogenetic therapy of dysentery and exclusion of antibiotic use for several years did not result in lower numbers of Shigella antibiotic resistant strains.     

Primary liver cancer in Cote d'Or (Burgundy). Results of three year's systematic registration in a well defined French population

The registry of digestive tract cancers set up for the department of Cote d'Or (455, 727) was used to study primary liver cancer. The crude annual incidence rate was 10.4 per 100 000 for males, 2.3 per 100 000 for females. Among other cancer registries annual age standardized rates: 7.6 per 100 000 in males, 1.4 per 100 000 in females are in the intermediate range, close to the figure reported in Geneva and higher than incidence rates reported elsewhere in Europe. Most cancers were hepatocullular carcinomas (83%). Significant etiological factors were the sex ratio (5, 4), alcoholic cirrhosis associated with primary liver cancer in 61% of the patients. The one year crude survival rate was 8%.     

The clinical laboratory assessment of vancomycin (Edicin) efficacy in treating suppurative wounds of the skin and soft tissues, burn wounds and the infectious complications of burns]

Clinical and bacteriological efficacies of vancomycin (Edicin, LEK) in the treatment of 17 patients with wound infection and 13 patients with thermal affections were studied. The clinical efficacy in the group of the patients with purulent wounds of the soft tissues amounted to 94.1 per cent and that in the patients with thermal affections was 92.3 per cent. The bacteriological effect was recorded in 86.6 per cent of the patients with purulent wounds of the soft tissues and in 69.3 per cent of the patients with burn infections. The drug intolerability was observed in two cases.     

Detection of Shigella antigens in the feces of patients with acute intestinal diseases using a coagglutination reaction

A total of 113 patients with acute intestinal diseases have been examined with the use of the coagglutination test. 84.95% of the patients showed the presence of different Shigella antigens. In patients with bacteriologically confirmed dysentery the corresponding Shigella antigens were detected in 96.97% of cases in S. sonnei dysentery, in 90% of cases in S. flexneri dysentery, in 75% of cases in S. newcastle dysentery and in 100% of bases in S. boydii dysentery. In 81.6% of patients with acute intestinal diseases of unknown etiology the coagglutination test revealed the presence of various Shigella antigens.     

Diarrhea, pneumonia, and infectious disease mortality in children aged 5 to 14 years in India

Background

Little is known about the causes of death in children in India after age five years. The objective of this study is to provide the first ever direct national and sub-national estimates of infectious disease mortality in Indian children aged 5 to 14 years.

Methods

A verbal autopsy based assessment of 3 855 deaths is children aged 5 to 14 years from a nationally representative survey of deaths occurring in 2001–03 in 1·1 million homes in India.

Results

Infectious diseases accounted for 58% of all deaths among children aged 5 to 14 years. About 18% of deaths were due to diarrheal diseases, 10% due to pneumonia, 8% due to central nervous system infections, 4% due to measles, and 12% due to other infectious diseases. Nationally, in 2005 about 59 000 and 34 000 children aged 5 to 14 years died from diarrheal diseases and pneumonia, corresponding to mortality of 24·1 and 13·9 per 100 000 respectively. Mortality was nearly 50% higher in girls than in boys for both diarrheal diseases and pneumonia.

Conclusions

Approximately 60% of all deaths in this age group are due to infectious diseases and nearly half of these deaths are due to diarrheal diseases and pneumonia. Mortality in this age group from infectious diseases, and diarrhea in particular, is much higher than previously estimated.     

Distribution of cancer mortality rates by province in South Africa

IntroductionCancer mortality rates are expected to increase in developing countries. Cancer mortality rates by province remain largely unreported in South Africa. This study described the 2014 age standardised cancer mortality rates by province in South Africa, to provide insight for strategic interventions and advocacy.Methods2014 deaths data were retrieved from Statistics South Africa. Deaths from cancer were extracted using 10th International Classification of Diseases (ICD) codes for cancer (C00-C97). Adjusted 2013 mid-year population estimates were used as a standard population. All rates were calculated per 100 000 individuals.ResultsNearly 38 000 (8%) of the total deaths in South Africa in 2014 were attributed to cancer. Western Cape Province had the highest age standardised cancer mortality rate in South Africa (118, 95% CI: 115–121 deaths per 100 000 individuals), followed by the Northern Cape (113, 95% CI: 107–119 per 100 000 individuals), with the lowest rate in Limpopo Province (47, 95% CI: 45–49 per 100 000). The age standardised cancer mortality rate for men (71, 95% CI: 70–72 per 100 000 individuals) was similar to women (69, 95% CI: 68–70 per 100 000). Lung cancer was a major driver of cancer death in men (13, 95% CI: 12.6–13.4 per 100 000). In women, cervical cancer was the leading cause of cancer death (13, 95% CI: 12.6–13.4 per 100 000 individuals).ConclusionThere is a need to further investigate the factors related to the differences in cancer mortality by province in South Africa. Raising awareness of risk factors and screening for cancer in the population along with improved access and quality of health care are also important.     

Research on Parvovirus B19 infections and chronic articular manifestations in a Tunisian hospital

Parvovirus B19 infection is often associated with acute and chronic joint diseases thus suggesting an etiologic role for the virus in these pathologies. In this work, we looked for a possible correlation between Parvovirus B19 infection and certain types of chronic inflammatory rheumatisms. We therefore, screened a population of 100 patients with different chronic inflammatory rheumatismal affections for serological markers of Parvovirus B19 infection. All patients were Tunisians of both sexes, who presented at the service of Rheumatology of the Charles Nicolle Hospital, Tunis. One hundred blood donors were taken as controls. Specific Immunoenzyme Assays of the ELISA type (Biotrin International, France) were used to detect anti-Parvovirus IgG and IgM. On the other hand, viral DNA was sought by nested PCR in synovial fluid from 14 patients. The data obtained indicate that specific anti-Parvovirus B19 IgG was detectable in the sera of 80.7% of patients and 43% of controls. In contrast, none of the sera was found positive for specific IgM antibodies. Synovial fluid samples could be collected from 14 anti-Parvovirus B19 seropositive patients and were tested for the presence of viral DNA. None of the samples was found positive. The results of our serological study reinforce the hypothesis that Parvovirus B19 infection is associated with rheumatismal joint affections. However, the lack of detectable viral DNA in synovial fluid of the tested seropositive patients points to an indirect role of the virus in these joint disorders.     

Haemolytic-uraemic syndrome complicating shigella dystentery in south Indian children.

Shigella dysentery caused 65% of all cases of acute renal failure (ARF) seen in children treated at the Christian Medical College Hospital, Vellore, during the 33 months ending September 1977. In the 40 children with ARF secondary to shigella dysentery, haematological findings suggested that they were suffering from the haemolytic-uraemic syndrome, and glomerular hypercellularity and fibrin deposition were present in all 12 patients whose renal histology could be studied. Peritoneal dialysis was the main element of treatment: 43% of children who underwent dialysis improved, compared with only 25% of those who did not undergo dialysis. The haemolytic-uraemic syndrome precipitated by bacillary dystentery is therefore the most important cause of ARF in children aged under 5 years in Tamil Nadu and the adjoining area of Andhra Pradesh.     

A 20-year prospective study of cirrhosis.

A total of 512 people from a defined population in west Birmingham served by a district general hospital were found to have cirrhosis in the period 1959-76. The annual incidence rose from 5.6 per 100 000 to a peak of 15.3 per 100 000 in 1974. This was due to an increase in the incidence of alcoholic cirrhosis, which in the last six years accounted for two-thirds of cases. The proportion of patients with decompensated cirrhosis when first seen (65%) did not alter during the 18 years. This was reflected in a death rate of 78% among the 468 patients traced up to the end of 1978. Liver failure, hepatoma, and gastrointestinal haemorrhage accounted for almost three-quarters of the deaths. The proportion of patients who survived for five years was 36% for alcoholic cirrhosis, 14% for cryptogenic cirrhosis, and 60% for chronic active hepatitis, and these figures too remained constant throughout the 18 years. Modern methods of treatment for decompensated cirrhosis did not improve prognosis and only abstention in patients with alcoholic cirrhosis had a beneficial effect on survival. Since alcoholic cirrhosis is now the most common form of the disease it is important to recognise those at risk and to encourage abstinence; also, more efforts are needed to identify the causes of cryptogenic cirrhosis. Whatever the cause, cirrhosis needs to be diagnosed before decompensation occurs, if treatment is to have any effect.     

Treatment of dysentery in children with a combination of monomycin and Eleutherococcus]

An acute dysentery process was studied in 100 children at the age of 1 to 14 years treated with monomycin; 54 patients (the 1st group) were treated with monomycin in combination with eleuterococcus and 46 patients (the 2nd group) were treated with monomycin alone. The dysentery process in the both groups was close. However, the increase in the levels of gamma-globulin, antidysentery antibodies and the phases of changes in the index of phagocytosis completeness during the disease were more pronounced in the patients of the 2nd group than those in the children of the 1st group. Recovery of the patients of the 1st group was registered earlier. It was concluded that eleuterococcus as an adaptagen provided recovery of the patients at lower efforts of the protection mechanisms. Wide use of eleuterococcus in combination with monomycin for the treatment of children with dysentery is recommended.     

Bringing Stem Cell‐Based Therapies for Type 1 Diabetes to the Clinic: Early Insights from Bioprocess Economics and Cost‐Effectiveness Analysis

Differentiation of pluripotent stem cells (PSCs) into β cells could provide insulin independence for type 1 diabetes (T1D) patients. This approach would reduce the clinical complications that most patients managed on intensive insulin therapy (IIT) face. However, bottlenecks of PSC manufacturing and limited engraftment of encapsulated cells hinder the long‐term effectiveness of these therapies. A bioprocess decision‐support tool is combined with a disease state‐transition model to evaluate the cost‐effectiveness of the stem cell‐based therapy against IIT. Clinical effectiveness is assessed in quality‐adjusted life years (QALYs). Manufacturing costs per patient reduce from $430 000 to $160 000 with optimization of batch size and annual demand. For 96% of the patients, cell therapy improves the quality of life compared to IIT. Cost savings are achieved for 2% of the population through prevention of renal disease. The therapy is cost‐effective for 3.4% of patients when a willingness to pay (WTP) of up to $150 000 per QALY is considered. A 75% cost reduction in the cell therapy price increases cost‐effectiveness likelihood to 51% at $100 000 per QALY. This study highlights the need for scalable manufacturing platforms for stem cell therapies, as well as to prioritizing access to the therapy to patients with an increased likelihood of costly complications.     

Agent-Based Model Forecasts Aging of the Population of People Who Inject Drugs in Metropolitan Chicago and Changing Prevalence of Hepatitis C Infections

People who inject drugs (PWID) are at high risk for blood-borne pathogens transmitted during the sharing of contaminated injection equipment, particularly hepatitis C virus (HCV). HCV prevalence is influenced by a complex interplay of drug-use behaviors, social networks, and geography, as well as the availability of interventions, such as needle exchange programs. To adequately address this complexity in HCV epidemic forecasting, we have developed a computational model, the Agent-based Pathogen Kinetics model (APK). APK simulates the PWID population in metropolitan Chicago, including the social interactions that result in HCV infection. We used multiple empirical data sources on Chicago PWID to build a spatial distribution of an in silico PWID population and modeled networks among the PWID by considering the geography of the city and its suburbs. APK was validated against 2012 empirical data (the latest available) and shown to agree with network and epidemiological surveys to within 1%. For the period 2010–2020, APK forecasts a decline in HCV prevalence of 0.8% per year from 44(±2)% to 36(±5)%, although some sub-populations would continue to have relatively high prevalence, including Non-Hispanic Blacks, 48(±5)%. The rate of decline will be lowest in Non-Hispanic Whites and we find, in a reversal of historical trends, that incidence among non-Hispanic Whites would exceed incidence among Non-Hispanic Blacks (0.66 per 100 per years vs 0.17 per 100 person years). APK also forecasts an increase in PWID mean age from 35(±1) to 40(±2) with a corresponding increase from 59(±2)% to 80(±6)% in the proportion of the population >30 years old. Our studies highlight the importance of analyzing subpopulations in disease predictions, the utility of computer simulation for analyzing demographic and health trends among PWID and serve as a tool for guiding intervention and prevention strategies in Chicago, and other major cities.     

The determination in saliva of IgA antibodies to Shigella ribosomes for the diagnosis of dysentery

The levels of antiribosomal antibodies to Shigella ribosomes in serum and saliva samples from 38 dysentery patients (15 S. sonnei cases and 23 S. flexneri cases), 14 patients with salmonellosis and 136 healthy adults were determined in ELISA with ribosomes from S. sonnei R-mutant used as solid-phase antigen. High levels of "normal" antiribosomal IgA, IgG and IgM antibodies were revealed in the sera of healthy persons while the level of salivary IgA antibodies was very low. In dysentery infection no increase in the levels of serum IgG and IgM antibodies and only a slight increase in the level of IgA antibodies were revealed. Local immune response was manifested by the early (on days 2-4 from the onset of infection) and significant augmentation (12- to 16-fold) of salivary antiribosomal IgA antibodies. An increase in the level of these antibodies was registered in 95-100% of dysentery patients but not in patients with salmonellosis, which made it possible to recommend the method for diagnosing shigellosis. Immune response to Shigella ribosomal antigens, in contrast to the response induced by Shigella O-antigen, is almost exclusively local.     

Impact of Maternal Country of Birth on Type-1-Diabetes Therapy and Outcome in 27,643 Children and Adolescents from the DPV Registry

Objective

To study the impact of maternal country of birth on type-1-diabetes (T1D) therapy and outcome.

Study Design and Methods

27,643 T1D patients aged ≤20 years with documented maternal country of birth from the multicenter German/Austrian diabetes patient registry (DPV) were analyzed. Patients were categorized based on their mother’s origin: Germany/Austria (reference), Turkey, Southern Europe, and Eastern Europe. To compare BMI standard deviation score (BMI-SDS), diabetes therapy and outcome between groups, multivariable regression was applied with adjustments for age, sex and duration of diabetes. Based on observed marginal frequencies, adjusted estimates were calculated. Linear regression was used for continuous data, logistic regression for binary data and Poisson regression for count data. All statistical analyses were performed using SAS 9.4. Significance was set at a two-tailed p<0.05.

Results

83.3% of patients were offspring of native mothers. A Turkish, Southern or Eastern European background was documented in 2.4%, 1.7% and 4.3% of individuals. After demographic adjustment, patients with migration background had a higher mean BMI-SDS (Turkey, Southern Europe or Eastern Europe vs. Germany/Austria: 0.58±0.03, 0.40±0.04, or 0.37±0.02 vs. 0.31±0.01; ±SE) and a lower use of insulin pumps (26.8%, 27.9%, or 32.6% vs. 37.9%) compared to offspring of native mothers. Mean HbA1c was worst in individuals of Turkish mothers (Turkey vs. Germany/Austria: 69.7±0.7 vs. 66.6±0.1 mmol/mol; ±SE). Patients of Eastern European descent had an increased rate of severe hypoglycemia (22.09±0.13 vs. 16.13±0.02 events per 100 patient-years) and ketoacidosis was more prevalent in offspring of Turkish or Southern European mothers (7.50±0.10, or 7.13±0.11 vs. 6.54±0.02 events per 100 patient-years). Patients of Turkish descent were more often hospitalized (57.2±2.7 vs. 48.5±0.4 per 100 patient-years). All differences were significant.

Conclusion

The differences in diabetes therapy and outcome among patients with distinct migration background suggest that specific challenges have to be considered in clinical care.     

Scaling up diarrhea prevention and treatment interventions: a Lives Saved Tool analysis

Background

Diarrhea remains a leading cause of mortality among young children in low- and middle-income countries. Although the evidence for individual diarrhea prevention and treatment interventions is solid, the effect a comprehensive scale-up effort would have on diarrhea mortality has not been estimated.

Methods and Findings

We use the Lives Saved Tool (LiST) to estimate the potential lives saved if two scale-up scenarios for key diarrhea interventions (oral rehydration salts [ORS], zinc, antibiotics for dysentery, rotavirus vaccine, vitamin A supplementation, basic water, sanitation, hygiene, and breastfeeding) were implemented in the 68 high child mortality countries. We also conduct a simple costing exercise to estimate cost per capita and total costs for each scale-up scenario. Under the ambitious (feasible improvement in coverage of all interventions) and universal (assumes near 100% coverage of all interventions) scale-up scenarios, we demonstrate that diarrhea mortality can be reduced by 78% and 92%, respectively. With universal coverage nearly 5 million diarrheal deaths could be averted during the 5-year scale-up period for an additional cost of US$12.5 billion invested across 68 priority countries for individual-level prevention and treatment interventions, and an additional US$84.8 billion would be required for the addition of all water and sanitation interventions.

Conclusion

Using currently available interventions, we demonstrate that with improved coverage, diarrheal deaths can be drastically reduced. If delivery strategy bottlenecks can be overcome and the international community can collectively deliver on the key strategies outlined in these scenarios, we will be one step closer to achieving success for the United Nations'' Millennium Development Goal 4 (MDG4) by 2015. Please see later in the article for the Editors'' Summary     

Nonelectrolyte penetration and sodium fluxes through the axolemma of resting and stimulated medium sized axons of the squid Doryteuthis plei

The penetration of ¹⁴C-labeled erythritol, mannitol, and sucrose through the axolemma was determined in medium sized paired axons, one at rest and the other stimulated 25 times per sec. The resting permeabilities, in 10^-7 cm/sec, are erythritol, 2.9 ± 0.3 (mean ± SEM); mannitol, 2.3 ± 0.4; and sucrose 0.9 ± 0.1. In the stimulated axons they are: erythritol, 5.2 ± 0.3; mannitol, 4.0 ± 0.5; and sucrose, 1.8 ± 0.3. Thus, the calculated permeabilities during activity (1 msec per impulse), in the same units, are: 100, 75, and 38, respectively. These changes in permeability are reversible. The effects of external potassium and sodium concentrations on erythritol penetration were also studied. At rest, erythritol penetration is independent of potassium and sodium concentrations. In the stimulated axons, erythritol penetration decreases when the extracellular sodium is diminished. Sodium influx (not the efflux) decreases during rest and activity when the extracellular sodium is diminished. The diminution during activity of erythritol and sodium entries in low sodium solutions may be related to a decrease of a drag effect of sodium ions on the nonelectrolyte molecules or to independent effects of the sodium concentration on sodium influx and the nonelectrolyte pathways. The axolemma discriminates among erythritol, mannitol, sucrose, and the different ionic species during rest and activity.