The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study

BackgroundIn 2013, a stockpile of oral cholera vaccine (OCV) was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both.ConclusionsReactive vaccination campaigns using a single dose of OCV may avert more cases and deaths than a standard two-dose campaign when vaccine supplies are limited, while at the same time reducing logistical complexity. These findings should motivate consideration of the trade-offs between one- and two-dose campaigns in resource-constrained settings, though further field efficacy data are needed and should be a priority in any one-dose campaign.     

Effect of Mass Supplementation with Ready-to-Use Supplementary Food during an Anticipated Nutritional Emergency

Background

Previous studies have shown the benefits of ready-to-use supplementary food (RUSF) distribution in reducing the incidence and prevalence of severe acute malnutrition.

Methods and Findings

To compare the incidence of wasting, stunting and mortality between children aged 6 to 23 mo participating and not participating in distributions of RUSF, we implemented two exhaustive prospective cohorts including all children 60 cm to 80 cm, resident in villages of two districts of Maradi region in Niger (n = 2238). Villages (20) were selected to be representative of the population. All registered children were eligible for the monthly distributions between July and October 2010. Age, sex, height, weight, and Mid-Upper Arm Circumference (MUAC) were measured at baseline and two weeks after each distribution; the amount and type of distribution and the amount shared and remaining were also assessed. We compared the incidence of wasting, stunting, and mortality among children participating in the distribution (intervention) of RUSF versus children not participating in the distribution (comparison). The absolute rate of wasting was 4.71 events per child-year (503 events/106.59 child-year) in the intervention group and 4.98 events per child-year (322 events/64.54 child-year) in the comparison group. The intervention group had a small but higher weight-for-length Z-score gain (−0.2z vs. −0.3z) and less loss of MUAC than the comparison group (−2.8 vs. −4.0 mm). There was no difference in length gain (2.7 vs. 2.8 cm). Mortality was lower for children whose households received the intervention than those who did not (adjusted HR 0.55, 95% CI: 0.32–0.98).

Conclusions

Short-term distribution with RUSF for children 6 to 23 months improve the nutritional status of children at risk for malnutrition. Fewer children who participated in the RUSF distribution died than those who did not.     

Does the Effectiveness of Control Measures Depend on the Influenza Pandemic Profile?

Background

Although strategies to contain influenza pandemics are well studied, the characterization and the implications of different geographical and temporal diffusion patterns of the pandemic have been given less attention.

Methodology/Main Findings

Using a well-documented metapopulation model incorporating air travel between 52 major world cities, we identified potential influenza pandemic diffusion profiles and examined how the impact of interventions might be affected by this heterogeneity. Clustering methods applied to a set of pandemic simulations, characterized by seven parameters related to the conditions of emergence that were varied following Latin hypercube sampling, were used to identify six pandemic profiles exhibiting different characteristics notably in terms of global burden (from 415 to >160 million of cases) and duration (from 26 to 360 days). A multivariate sensitivity analysis showed that the transmission rate and proportion of susceptibles have a strong impact on the pandemic diffusion. The correlation between interventions and pandemic outcomes were analyzed for two specific profiles: a fast, massive pandemic and a slow building, long-lasting one. In both cases, the date of introduction for five control measures (masks, isolation, prophylactic or therapeutic use of antivirals, vaccination) correlated strongly with pandemic outcomes. Conversely, the coverage and efficacy of these interventions only moderately correlated with pandemic outcomes in the case of a massive pandemic. Pre-pandemic vaccination influenced pandemic outcomes in both profiles, while travel restriction was the only measure without any measurable effect in either.

Conclusions

Our study highlights: (i) the great heterogeneity in possible profiles of a future influenza pandemic; (ii) the value of being well prepared in every country since a pandemic may have heavy consequences wherever and whenever it starts; (iii) the need to quickly implement control measures and even to anticipate pandemic emergence through pre-pandemic vaccination; and (iv) the value of combining all available control measures except perhaps travel restrictions.     

Histopathological effects of cisplatin,doxorubicin and 5-flurouracil (5-FU) on the liver of male albino rats

Cisplatin, doxorubicin and fluorouracil (5-FU), drugs belonging to different chemical classes, have been extensively used for chemotherapy of various cancers. Despite extensive investigations into their hepatotoxicity, there is very limited information on their effects on the structure and ultra-structure of liver cells in vivo. Here, we demonstrate for the first time, the effects of these three anticancer drugs on rat liver toxicity using both light and electron microscopy. Light microscopic observations revealed that higher doses of cisplatin and doxorubicin caused massive hepatotoxicity compared to 5-FU treatment, including dissolution of hepatic cords, focal inflammation and necrotic tissues. Interestingly, low doses also exhibited abnormal changes, including periportal fibrosis, degeneration of hepatic cords and increased apoptosis. These changes were confirmed at ultrastructural level, including vesiculated rough endoplasmic reticulum and atrophied mitochondria with ill-differentiated cisternae, dense collection of macrophages and lymphocytes as well as fibrocytes with collagenous fibrils manifesting early sign of fibrosis, especially in response to cisplatin and doxorubicin -treatment. Our results provide in vivo evidence, at ultrastructural level, of direct hepatotoxicity caused by cisplatin, doxorubicin and 5-FU at both light and electron microscopi. These results can guide the design of appropriate treatment regimen to reduce the hepatotoxic effects of these anticancer drugs.     

The Ras guanine nucleotide exchange factor RasGRF1 promotes matrix metalloproteinase-3 production in rheumatoid arthritis synovial tissue

Introduction  

Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients share many similarities with transformed cancer cells, including spontaneous production of matrix metalloproteinases (MMPs). Altered or chronic activation of proto-oncogenic Ras family GTPases is thought to contribute to inflammation and joint destruction in RA, and abrogation of Ras family signaling is therapeutic in animal models of RA. Recently, expression and post-translational modification of Ras guanine nucleotide releasing factor 1 (RasGRF1) was found to contribute to spontaneous MMP production in melanoma cancer cells. Here, we examine the potential relationship between RasGRF1 expression and MMP production in RA, reactive arthritis, and inflammatory osteoarthritis synovial tissue and FLS.     

Mortality Risk among Children Admitted in a Large-Scale Nutritional Program in Niger, 2006

Background

In 2006, the Médecins sans Frontières nutritional program in the region of Maradi (Niger) included 68,001 children 6–59 months of age with either moderate or severe malnutrition, according to the NCHS reference (weight-for-height<80% of the NCHS median, and/or mid-upper arm circumference<110 mm for children taller than 65 cm and/or presence of bipedal edema). Our objective was to identify baseline risk factors for death among children diagnosed with severe malnutrition using the newly introduced WHO growth standards. As the release of WHO growth standards changed the definition of severe malnutrition, which now includes many children formerly identified as moderately malnourished with the NCHS reference, studying this new category of children is crucial.

Methodology

Program monitoring data were collected from the medical records of all children admitted in the program. Data included age, sex, height, weight, MUAC, clinical signs on admission including edema, and type of discharge (recovery, death, and default/loss to follow up). Additional data included results of a malaria rapid diagnostic test due to Plasmodium falciparum (Paracheck®) and whether the child was a resident of the region of Maradi or came from bordering Nigeria to seek treatment. Multivariate logistic regression was performed on a subset of 27,687 children meeting the new WHO growth standards criteria for severe malnutrition (weight-for-height<−3 Z score, mid-upper arm circumference<110 mm for children taller than 65 cm or presence of bipedal edema). We explored two different models: one with only basic anthropometric data and a second model that included perfunctory clinical signs.

Principal Findings

In the first model including only weight, height, sex and presence of edema, the risk factors retained were the weight/height^1.84 ratio (OR: 5,774; 95% CI: [2,284; 14,594]) and presence of edema (7.51 [5.12; 11.0]). A second model, taking into account supplementary data from perfunctory clinical examination, identified other risk factors for death: apathy (9.71 [6.92; 13.6]), pallor (2.25 [1.25; 4.05]), anorexia (1.89 [1.35; 2.66]), fever>38.5°C (1.83 [1.25; 2.69]), and age below 1 year (1.42 [1.01; 1.99]).

Conclusions

Although clinicians will continue to perform screening using clinical signs and anthropometry, these risk indicators may provide additional criteria for the assessment of absolute and relative risk of death. Better appraisal of the child''s risk of death may help orientate the child towards either hospitalization or ambulatory care. As the transition from the NCHS growth reference to the WHO standards will increase the number of children classified as severely malnourished, further studies should explore means to identify children at highest risk of death within this group using simple and standardized indicators.     

Prevalence and Risk Factors of Lassa Seropositivity in Inhabitants of the Forest Region of Guinea: A Cross-Sectional Study

Background

Lassa fever is a viral hemorrhagic fever endemic in West Africa. The reservoir host of the virus is a multimammate rat, Mastomys natalensis. Prevalence estimates of Lassa virus antibodies in humans vary greatly between studies, and the main modes of transmission of the virus from rodents to humans remain unclear. We aimed to (i) estimate the prevalence of Lassa virus–specific IgG antibodies (LV IgG) in the human population of a rural area of Guinea, and (ii) identify risk factors for positive LV IgG.

Methods and Findings

A population-based cross-sectional study design was used. In April 2000, all individuals one year of age and older living in three prefectures located in the tropical secondary forest area of Guinea (Gueckedou, Lola and Yomou) were sampled using two-stage cluster sampling. For each individual identified by the sampling procedure and who agreed to participate, a standardized questionnaire was completed to collect data on personal exposure to potential risk factors for Lassa fever (mainly contact with rodents), and a blood sample was tested for LV IgG. A multiple logistic regression model was used to determine risk factors for positive LV IgG. A total of 1424 subjects were interviewed and 977 sera were tested. Prevalence of positive LV Ig was of 12.9% [10.8%–15.0%] and 10.0% [8.1%–11.9%] in rural and urban areas, respectively. Two risk factors of positive LV IgG were identified: to have, in the past twelve months, undergone an injection (odds ratio [OR] = 1.8 [1.1–3.1]), or lived with someone displaying a haemorrhage (OR = 1.7 [1.1–2.9]). No factors related to contacts with rats and/or mice remained statistically significant in the multivariate analysis.

Conclusions

Our study underlines the potential importance of person-to-person transmission of Lassa fever, via close contact in the same household or nosocomial exposure.     

Natural occurrence of deoxynivalenol, 3-acetyl-deoxynivalenol, 15-acetyl-deoxynivalenol,nivalenol, 4,7-dideoxynivalenol,and zearalenone in polish wheat

Three wheat samples collected in 1987 in Central Poland and naturally infected withFusarium spp were analyzed for the presence ofFusarium spp andFusarium toxins. Heads were separated into three fractions: kernels with visibleFusarium damage, healthy looking kernels, and chaff + rachis. The samples contained deoxynivalenol (2.0 – 40.0μg/g), nivalenol (O.O1μg/g), 4,7-dideoxynivalenol (0.10 – 0.15μg/g). 15-acetyldeoxynivalenol (0.10–2.00 μg/g), 3-acetyldeoxynivalenol (O/1Oμg/g), and zearalenone (0.01–2.00μg/g). This is the first report about 15 - acetyldeoxynivalenol in European wheat and the co-occurrence of 3 - acetyldeoxynivalenol and 15-acetyldeoxynivalenol in the same sample of contaminated cereals.