Use of oral cholera vaccines in an outbreak in Vietnam: a case control study

Background

Killed oral cholera vaccines (OCVs) are available but not used routinely for cholera control except in Vietnam, which produces its own vaccine. In 2007–2008, unprecedented cholera outbreaks occurred in the capital, Hanoi, prompting immunization in two districts. In an outbreak investigation, we assessed the effectiveness of killed OCV use after a cholera outbreak began.

Methodology/Principal Findings

From 16 to 28 January 2008, vaccination campaigns with the Vietnamese killed OCV were held in two districts of Hanoi. No cholera cases were detected from 5 February to 4 March 2008, after which cases were again identified. Beginning 8 April 2008, residents of four districts of Hanoi admitted to one of five hospitals for acute diarrhea with onset after 5 March 2008 were recruited for a matched, hospital-based, case-control outbreak investigation. Cases were matched by hospital, admission date, district, gender, and age to controls admitted for non-diarrheal conditions. Subjects from the two vaccinated districts were evaluated to determine vaccine effectiveness. 54 case-control pairs from the vaccinated districts were included in the analysis. There were 8 (15%) and 16 (30%) vaccine recipients among cases and controls, respectively. The vaccine was 76% protective against cholera in this setting (95% CI 5% to 94%, P = 0.042) after adjusting for intake of dog meat or raw vegetables and not drinking boiled or bottled water most of the time.

Conclusions/Significance

This is the first study to explore the effectiveness of the reactive use of killed OCVs during a cholera outbreak. Our findings suggest that killed OCVs may have a role in controlling cholera outbreaks.     

Age is an independent risk factor for left atrial dysfunction: results from an observational study

Introduction. The degenerative changes of myocardial tissue are thought to influence left atrial (LA) function. Changes of left atrial function are generally due to changes in left ventricle (LV) compliance. But valvular dysfunction and hypertension as comorbidity cannot be ignored. Women have a different clinical profile compared with men concerning the risk of heart failure. We investigated the influence of increasing age and gender corrected for comorbidity, on left atrial function. Methods. Using an open access echocardiography database, supplemented with additional LA function measurements, we defined three different LA function parameters. Odds ratios (OR) were calculated to reproduce the relation between age, gender and LA function. The association between age, gender and LA function was estimated, and corrected for comorbid conditions as valve disease, high blood pressure and LV dysfunction, using logistic regression. Results. Higher age was positively correlated with increased LA volume, decreased ejection fraction and increased LA kinetic energy. Age per decade increase, corrected for comorbidity, resulted in an increased risk of LA dysfunction (OR between 1.5 and 1.9). Gender had little influence on LA function parameters except for LA maximal volume. Men had a significantly larger LA maximal volume compared with women. Conclusions. In this open access echocardiography database, increasing age was correlated with LA dysfunction. Age per decade increase, corrected for comorbid conditions such as mitral and aortic valve disease, hypertension and heart failure, is an independent risk factor for LA dysfunction. The gender influence on LA dysfunction seems to be limited. (Neth Heart J 2010;18:243-7.)     

Optimizing one-dose and two-dose cholera vaccine allocation in outbreak settings: A modeling study

BackgroundA global stockpile of oral cholera vaccine (OCV) was established in 2013 for use in outbreak response and are licensed as two-dose regimens. Vaccine availability, however, remains limited. Previous studies have found that a single dose of OCV may provide substantial protection against cholera.MethodsUsing a mathematical model with two age groups paired with optimization algorithms, we determine the optimal vaccination strategy with one and two doses of vaccine to minimize cumulative overall infections, symptomatic infections, and deaths. We explore counterfactual vaccination scenarios in three distinct settings: Maela, the largest refugee camp in Thailand, with high in- and out-migration; N’Djamena, Chad, a densely populated region; and Haiti, where departments are connected by rivers and roads.ResultsOver the short term under limited vaccine supply, the optimal strategies for all objectives prioritize one dose to the older age group (over five years old), irrespective of setting and level of vaccination coverage. As more vaccine becomes available, it is optimal to administer a second dose for long-term protection. With enough vaccine to cover the whole population with one dose, the optimal strategies can avert up to 30% to 90% of deaths and 36% to 92% of symptomatic infections across the three settings over one year. The one-dose optimal strategies can avert 1.2 to 1.8 times as many cases and deaths compared to the standard two-dose strategy.ConclusionsIn an outbreak setting, speedy vaccination campaigns with a single dose of OCV is likely to avert more cases and deaths than a two-dose pro-rata campaign under a limited vaccine supply.     

An evolutionary computing approach for parameter estimation investigation of a model for cholera

We consider the problem of using time-series data to inform a corresponding deterministic model and introduce the concept of genetic algorithms (GA) as a tool for parameter estimation, providing instructions for an implementation of the method that does not require access to special toolboxes or software. We give as an example a model for cholera, a disease for which there is much mechanistic uncertainty in the literature. We use GA to find parameter sets using available time-series data from the introduction of cholera in Haiti and we discuss the value of comparing multiple parameter sets with similar performances in describing the data.     

Inference for constrained estimation of tumor size distributions

SUMMARY: In order to develop better treatment and screening programs for cancer prevention programs, it is important to be able to understand the natural history of the disease and what factors affect its progression. We focus on a particular framework first outlined by Kimmel and Flehinger (1991, Biometrics, 47, 987-1004) and in particular one of their limiting scenarios for analysis. Using an equivalence with a binary regression model, we characterize the nonparametric maximum likelihood estimation procedure for estimation of the tumor size distribution function and give associated asymptotic results. Extensions to semiparametric models and missing data are also described. Application to data from two cancer studies is used to illustrate the finite-sample behavior of the procedure.     

The characteristics of a cholera outbreak in Pushkino District, the Azerbaijan SSR

The outbreak of cholera in the Pushkino District of the Azerbaijan SSR, caused by the penetration of Vibrio cholerae into the water of the irrigation system, is described. Altogether 2 cholera patients and 39 Vibrio carriers were detected. The etiological agent of this infection was V. cholerae eltor, serovar Ogawa, with typical phenotype characteristics. From all patients and 37 carriers virulent strains and from 2 carriers faintly virulent strains were isolated. In this outbreak family foci were clearly observed, but the transmission of infection through everyday contacts was practically of no importance. The foci with multiple cases were formed due to the action of one transmission factor: contaminated water.     

A prescribing incentive scheme for non-fundholding general practices: an observational study.

OBJECTIVE: To examine the effects of a financial incentive scheme on prescribing in non-fundholding general practices. DESIGN: Observational study. SETTING: Non-fundholding general practices in former Northern region in 1993-4. INTERVENTION: Target savings were set for each group of practices; those that achieved them were paid a portion of the savings. MAIN OUTCOME MEASURES: Financial performance; prescribing patterns in major therapeutic groups and some specific therapeutic areas; rates of generic prescribing; and performance against a measure of prescribing quality. SUBJECTS: 459 non-fundholding general practices, grouped into three bands according to the ratio of their indicative prescribing amount to the local average (band A > or = 10% above average, B between average and 10% above, C below average). RESULTS: 102 (23%) of 442 practices achieved their target savings (18%, 19%, and 27% of bands A, B, and C respectively). Band C practices that achieved their target had a lower per capita prescribing frequency for gastrointestinal drugs, inhaled steroids, antidepressants, and hormone replacement therapy. There were no other significant differences in prescribing frequency, and no reduction in the quality of prescribing in achieving practices. Total savings of pounds 1.54 m on indicative prescribing amounts were achieved. Payments from the incentive scheme and discretionary quality awards resulted in pounds 463,000 being returned to practices for investment in primary care. CONCLUSIONS: The prescribing behaviour of non-fundholding general practitioners responded to financial incentives in a similar way to that of fundholding practitioners. The incentive scheme did not seem to reduce the quality of prescribing.     

Valproic acid is associated with cognitive decline in HIV-infected individuals: a clinical observational study

Background  

Valproic acid (VPA) is often used to control pain in HIV-related neuropathy. However, the effect of VPA on cognitive functions in advanced HIV-infected individuals is largely unknown. A recent study would suggest that it may have a neuroprotective effect, the doses used were low and the observation period short.     

Influenza virus in human exhaled breath: an observational study

Background

Recent studies suggest that humans exhale fine particles during tidal breathing but little is known of their composition, particularly during infection.

Methodology/Principal Findings

We conducted a study of influenza infected patients to characterize influenza virus and particle concentrations in their exhaled breath. Patients presenting with influenza-like-illness, confirmed influenza A or B virus by rapid test, and onset within 3 days were recruited at three clinics in Hong Kong, China. We collected exhaled breath from each subject onto Teflon filters and measured exhaled particle concentrations using an optical particle counter. Filters were analyzed for influenza A and B viruses by quantitative polymerase chain reaction (qPCR). Twelve out of thirteen rapid test positive patients provided exhaled breath filter samples (7 subjects infected with influenza B virus and 5 subjects infected with influenza A virus). We detected influenza virus RNA in the exhaled breath of 4 (33%) subjects–three (60%) of the five patients infected with influenza A virus and one (14%) of the seven infected with influenza B virus. Exhaled influenza virus RNA generation rates ranged from <3.2 to 20 influenza virus RNA particles per minute. Over 87% of particles exhaled were under 1 µm in diameter.

Conclusions

These findings regarding influenza virus RNA suggest that influenza virus may be contained in fine particles generated during tidal breathing, and add to the body of literature suggesting that fine particle aerosols may play a role in influenza transmission.     

Voluntary activation failure is detectable in some myositis patients with persisting quadriceps femoris weakness: an observational study

This cross-sectional, observational study was undertaken to examine whether voluntary activation failure could contribute to the persisting weakness observed in some patients with treated idiopathic inflammatory myositis. In 20 patients with myositis of more than six months' duration (5 males, 15 females; mean [± 1 SD] age 53 [11] years) and 102 normal subjects (44 males, 58 females; mean age 32 [8] years), isometric maximum voluntary contractions (MVCs) of the dominant quadriceps femoris (QF) were quantified. Absolute MVC results of normal subjects and patients were then normalised with respect to lean body mass (force per units of lean body mass), giving a result in Newtons per kilogram. Based on mass-normalised force data of normal subjects, patients were arbitrarily stratified into "weak" and "not weak" subgroups. During further MVC attempts, the "twitch interpolation" technique was used to assess whether the QF voluntary activation of patients was complete. This technique relies on the fact that, because muscle activation is incomplete during submaximal voluntary contractions, electrical stimulation of the muscle can induce force increments superimposed on the submaximal voluntary force being generated. No between-gender differences were seen in the mass-normalised MVC results of healthy subjects, so the gender-combined results of 6.6 (1.5) N/kg were used for patient stratification. No between-gender difference was found for mass-normalised MVCs in patients: males 5.4 (3.2) and females 3.0 (1.7) N/kg (p > 0.05). Mass-normalised MVCs of male patients were as great as those of normal subjects (p > 0.05), but mass-normalised MVCs of female patients were significantly smaller than those of the normal subjects (p < 0.001). Only one of the six "not weak" patients exhibited interpolated twitches during electrical stimulation, but six of the 14 "weak" patients did, the biggest twitches being seen in the weakest patient. That interpolated twitches can be induced in some myositis patients with ongoing QF weakness during supposed MVCs clearly suggests that voluntary activation failure does contribute to QF weakness in those patients.     

Controlling tungiasis in an impoverished community: an intervention study

Background

In Brazil, tungiasis is endemic in some resource-poor communities where various domestic and sylvatic animals act as reservoirs for this zoonosis. To determine the effect of control measures on the prevalence and intensity of infestation of human and animal tungiasis, a repeated cross-sectional survey with intervention was carried out.

Methodology/Principal Findings

In a traditional fishing community in Northeast Brazil, humans and reservoir animals were treated, and premise-spraying using an insecticide was done, while a second fishing community served as a control. Both communities were followed up 10 times during a 12-month period. At baseline, prevalence of tungiasis was 43% (95% confidence interval [CI]: 35%–51%) and 37% (95% CI: 31%–43%) in control and intervention villages, respectively. During the study, prevalence of tungiasis dropped to 10% (95% CI: 8%–13%; p<0.001) in the intervention village, while the prevalence remained at a high level in the control village. However, after one year, at the end of the study, in both communities the prevalence of the infestation had reached pre-intervention levels. Whereas the intensity of infestation was significantly reduced in the intervention community (p<0.001), and remained low at the end of the study (p<0.001), it did not change in the control village.

Conclusion/Significance

Our study shows that a reduction of prevalence and intensity of infestation is possible, but in impoverished communities a long-lasting reduction of disease occurrence can only be achieved by the regular treatment of infested humans, the elimination of animal reservoirs, and, likely, through environmental changes.

Trial Registration

Controlled-Trials.com ISRCTN27670575     

Carotid bruits as predictor for carotid stenoses detected by ultrasonography: an observational study

Background  

Carotid surgery in asymptomatic subjects with carotid stenosis is effective to prevent ischemic stroke. There is, however, uncertainty how to find such persons at risk, because mass screening with carotid artery ultrasonography (US) is not cost-effective. Signs of carotid bruits corresponding to the carotid arteries may serve as a tool to select subjects for further investigation. This study is thus aimed at determining the usefulness of carotid bruits in the screening of carotid stenoses.     

Economic impact of a nationwide outbreak of salmonellosis: cost-benefit of early intervention.

The recognition and investigation of an outbreak of food poisoning in 1982 due to chocolate contaminated with Salmonella napoli enabled the food that carried the salmonella to be identified and four fifths of the implicated consignment of chocolate to be withdrawn. The economic benefits of prompt intervention in the outbreak have been assessed. The cost of the outbreak was over 0.5 pounds m. It is estimated that five deaths were prevented by the intervention and that 185 admissions to hospital and 29,000 cases of S napoli enteritis were avoided. This successful investigation yielded a 3.5-fold rate of return to the public sector and a 23.3-fold return to society on an investment in public health surveillance. A methodology is described that can be used to estimate the benefits of early intervention in outbreaks of foodborne illness and topics for further research are suggested. It is concluded that public health authorities and industry have much to gain by collaborating in the research into the design of cost effective programmes to prevent foodborne infections.