True versus apparent malaria infection prevalence: the contribution of a Bayesian approach

Aims

To present a new approach for estimating the “true prevalence” of malaria and apply it to datasets from Peru, Vietnam, and Cambodia.

Methods

Bayesian models were developed for estimating both the malaria prevalence using different diagnostic tests (microscopy, PCR & ELISA), without the need of a gold standard, and the tests'' characteristics. Several sources of information, i.e. data, expert opinions and other sources of knowledge can be integrated into the model. This approach resulting in an optimal and harmonized estimate of malaria infection prevalence, with no conflict between the different sources of information, was tested on data from Peru, Vietnam and Cambodia.

Results

Malaria sero-prevalence was relatively low in all sites, with ELISA showing the highest estimates. The sensitivity of microscopy and ELISA were statistically lower in Vietnam than in the other sites. Similarly, the specificities of microscopy, ELISA and PCR were significantly lower in Vietnam than in the other sites. In Vietnam and Peru, microscopy was closer to the “true” estimate than the other 2 tests while as expected ELISA, with its lower specificity, usually overestimated the prevalence.

Conclusions

Bayesian methods are useful for analyzing prevalence results when no gold standard diagnostic test is available. Though some results are expected, e.g. PCR more sensitive than microscopy, a standardized and context-independent quantification of the diagnostic tests'' characteristics (sensitivity and specificity) and the underlying malaria prevalence may be useful for comparing different sites. Indeed, the use of a single diagnostic technique could strongly bias the prevalence estimation. This limitation can be circumvented by using a Bayesian framework taking into account the imperfect characteristics of the currently available diagnostic tests. As discussed in the paper, this approach may further support global malaria burden estimation initiatives.     

World Health Organization Global Estimates and Regional Comparisons of the Burden of Foodborne Disease in 2010

Illness and death from diseases caused by contaminated food are a constant threat to public health and a significant impediment to socio-economic development worldwide. To measure the global and regional burden of foodborne disease (FBD), the World Health Organization (WHO) established the Foodborne Disease Burden Epidemiology Reference Group (FERG), which here reports their first estimates of the incidence, mortality, and disease burden due to 31 foodborne hazards. We find that the global burden of FBD is comparable to those of the major infectious diseases, HIV/AIDS, malaria and tuberculosis. The most frequent causes of foodborne illness were diarrheal disease agents, particularly norovirus and Campylobacter spp. Diarrheal disease agents, especially non-typhoidal Salmonella enterica, were also responsible for the majority of deaths due to FBD. Other major causes of FBD deaths were Salmonella Typhi, Taenia solium and hepatitis A virus. The global burden of FBD caused by the 31 hazards in 2010 was 33 million Disability Adjusted Life Years (DALYs); children under five years old bore 40% of this burden. The 14 subregions, defined on the basis of child and adult mortality, had considerably different burdens of FBD, with the greatest falling on the subregions in Africa, followed by the subregions in South-East Asia and the Eastern Mediterranean D subregion. Some hazards, such as non-typhoidal S. enterica, were important causes of FBD in all regions of the world, whereas others, such as certain parasitic helminths, were highly localised. Thus, the burden of FBD is borne particularly by children under five years old–although they represent only 9% of the global population–and people living in low-income regions of the world. These estimates are conservative, i.e., underestimates rather than overestimates; further studies are needed to address the data gaps and limitations of the study. Nevertheless, all stakeholders can contribute to improvements in food safety throughout the food chain by incorporating these estimates into policy development at national and international levels.

Summary Points

• Thirty-one foodborne hazards caused 600 (95% uncertainty interval [UI] 420–960) million foodborne illnesses and 420,000 (95% UI 310,000–600,000) deaths in 2010.
• The global burden of FBD caused by the 31 hazards studied was 33 (95% UI 25–46) million DALYs in 2010.
• The most frequent causes of foodborne illness were diarrheal disease agents; particularly norovirus and Campylobacter spp.
• Foodborne diarrheal disease agents, particularly non-typhoidal Salmonella enterica, caused 230,000 (95% UI 160,000–320,000) deaths
• Other major causes of FBD deaths were Salmonella Typhi, Taenia solium, hepatitis A virus and aflatoxin.
• 40% of the FBD burden was among children under 5 years old.
• The African (AFR), South-East Asian (SEAR) and Eastern Mediterranean (EMR) D subregions had the highest FBD burden.
• Diarrheal disease agents were the leading cause of FBD burden in most subregions, and non-typhoidal Salmonella enterica caused an important burden in all subregions, particularly in the subregions in Africa.
• Other main causes of diarrheal FBD burden were enteropathogenic Escherichia coli, enterotoxigenic Escherichia coli and Vibrio cholerae in low-income subregions, and Campylobacter spp. in high-income subregions.
• The burden of aflatoxin was high in the AFR D, Western Pacific (WPR) B and SEAR B subregions, whereas dioxins caused the highest burden in SEAR D, EMR D and European (EUR) A and C subregions.
• In the South-East Asian subregions, there was a considerable burden of Salmonella Typhi; the burden of Opisthorchis spp. was concentrated in the SEAR B region, where the seafoodborne trematodes Paragonimus spp. and Clonorchis sinensis were also important.
• In Central and South American (AMR B and AMR D) subregions, T. solium and Toxoplasma gondii contributed significantly to the FBD burden.
• These estimates should inform policy development at national and international levels to improve food safety throughout the food chain.

     

Successful Outcome of Disseminated Fusarium musae Fungemia with Skin Localization Treated with Liposomal Amphotericin B and Voriconazole in a Patient with Acute Myeloid Leukemia

Fusarium spp. may cause invasive disseminated infections in immunocompromised patients, associated with significant morbidity and mortality. We describe a case of disseminated fusariosis with fungemia and skin localization caused by Fusarium musae in a patient with acute myeloid leukemia successfully treated using liposomal amphotericin B and voriconazole.

     

Carbon monoxide prevents hepatic mitochondrial membrane permeabilization

Background  

Low concentrations of carbon monoxide (CO) protect hepatocytes against apoptosis and confers cytoprotection in several models of liver. Mitochondria are key organelles in cell death control via their membrane permeabilization and the release of pro-apoptotic factors.     

Taenia solium Infections in a rural area of Eastern Zambia-a community based study

Background

Taenia solium taeniosis/cysticercosis is a parasitic infection occurring in many developing countries. Data on the status of human infections in Zambia is largely lacking. We conducted a community-based study in Eastern Zambia to determine the prevalence of human taeniosis and cysticercosis in a rural community.

Methods and Findings

Stool and serum samples were collected from willing participants. Geographical references of the participants'' households were determined and household questionnaires administered. Taeniosis was diagnosed in stool samples by coprology and by the polyclonal antibody-based copro-antigen enzyme-linked immunosorbent assay (copro-Ag ELISA), while cysticercosis was diagnosed in serum by the B158/B60 monoclonal antibody-based antigen ELISA (sero-Ag ELISA). Identification of the collected tapeworm after niclosamide treatment and purgation was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A total of 255 households from 20 villages participated in the study, 718 stool and 708 serum samples were collected and examined. Forty-five faecal samples (6.3%) were found positive for taeniosis on copro-Ag ELISA while circulating cysticercus antigen was detected in 5.8% (41/708) individuals. The tapeworm recovered from one of the cases was confirmed to be T. solium on PCR-RFLP. Seropositivity (cysticercosis) was significantly positively related to age (p = 0.00) and to copro-Ag positivity (taeniosis) (p = 0.03) but not to gender. Change point analysis revealed that the frequency of cysticercus antigens increased significantly in individuals above the age of 30. Copro-Ag positivity was not related to age or gender. The following risk factors were noted to be present in the study community: free-range pig husbandry system and poor sanitation with 47.8% of the households visited lacking latrines.

Conclusions

This study has recorded high taeniosis and cysticercosis prevalences and identified the need for further studies on transmission dynamics and impact of the disease on the local people.     

Multimodal imaging of stem cell implantation in the central nervous system of mice

During the past decade, stem cell transplantation has gained increasing interest as primary or secondary therapeutic modality for a variety of diseases, both in preclinical and clinical studies. However, to date results regarding functional outcome and/or tissue regeneration following stem cell transplantation are quite diverse. Generally, a clinical benefit is observed without profound understanding of the underlying mechanism(s). Therefore, multiple efforts have led to the development of different molecular imaging modalities to monitor stem cell grafting with the ultimate aim to accurately evaluate survival, fate and physiology of grafted stem cells and/or their micro-environment. Changes observed in one or more parameters determined by molecular imaging might be related to the observed clinical effect. In this context, our studies focus on the combined use of bioluminescence imaging (BLI), magnetic resonance imaging (MRI) and histological analysis to evaluate stem cell grafting. BLI is commonly used to non-invasively perform cell tracking and monitor cell survival in time following transplantation, based on a biochemical reaction where cells expressing the Luciferase-reporter gene are able to emit light following interaction with its substrate (e.g. D-luciferin). MRI on the other hand is a non-invasive technique which is clinically applicable and can be used to precisely locate cellular grafts with very high resolution, although its sensitivity highly depends on the contrast generated after cell labeling with an MRI contrast agent. Finally, post-mortem histological analysis is the method of choice to validate research results obtained with non-invasive techniques with highest resolution and sensitivity. Moreover end-point histological analysis allows us to perform detailed phenotypic analysis of grafted cells and/or the surrounding tissue, based on the use of fluorescent reporter proteins and/or direct cell labeling with specific antibodies. In summary, we here visually demonstrate the complementarities of BLI, MRI and histology to unravel different stem cell- and/or environment-associated characteristics following stem cell grafting in the CNS of mice. As an example, bone marrow-derived stromal cells, genetically engineered to express the enhanced Green Fluorescent Protein (eGFP) and firefly Luciferase (fLuc), and labeled with blue fluorescent micron-sized iron oxide particles (MPIOs), will be grafted in the CNS of immune-competent mice and outcome will be monitored by BLI, MRI and histology (Figure 1).     

Fulminant cryptosporidiosis after near-drowning: a human Cryptosporidium parvum strain implicated in invasive gastrointestinal adenocarcinoma and cholangiocarcinoma in an experimental model

In the present work, we report the characterization of a Cryptosporidium parvum strain isolated from a patient who nearly drowned in the Deule River (Lille, France) after being discharged from the hospital where he had undergone allogeneic stem cell transplantation. After being rescued and readmitted to the hospital, he developed fulminant cryptosporidiosis. The strain isolated from the patient's stools was identified as C. parvum II2A15G2R1 (subtype linked to zoonotic exposure) and inoculated into SCID mice. In this host, this virulent C. parvum isolate induced not only severe infection but also invasive gastrointestinal and biliary adenocarcinoma. The observation of adenocarcinomas that progressed through all layers of the digestive tract to the subserosa and spread via blood vessels confirmed the invasive nature of the neoplastic process. These results indicate for the first time that a human-derived C. parvum isolate is able to induce digestive cancer. This study is of special interest considering the exposure of a large number of humans and animals to this waterborne protozoan, which is highly tumorigenic when inoculated in a rodent model.     

Circulating surfactant protein D as a potential lung-specific biomarker of health outcomes in COPD: a pilot study

Background

There is a paucity of surrogate lung-specific biological markers that can be used to track disease progression and predict clinical outcomes in chronic obstructive pulmonary disease (COPD). The principal aim of this pilot study was to determine whether circulating surfactant protein D (SPD) or Clara Cell protein-16 (CC16) levels are associated with lung function or health status in patients with severe COPD.

Methods

We studied 23 patients with advanced COPD. Lung function measurements, Chronic Respiratory Disease Questionnaire (CRQ) scores, and serum levels of SPD, CC16, and C-reactive protein (CRP) were determined at baseline and at 3 months.

Results

At baseline, FEV₁ was inversely associated with serum SPD levels (P = 0.045) but not with CC16 (P = 0.675) or CRP levels (P = 0.549). Over a 3 month period, changes in SPD levels correlated significantly with changes in CRQ scores (adjusted P = 0.008) such that patients who had the largest declines in serum SPD levels experienced the largest gains in health status. The association was particularly notable between circulating SPD level and the dyspnea domain of the CRQ score (P = 0.018). Changes in CC16 or CRP levels did not correlate with changes in CRQ scores.

Conclusion

Changes in serum SPD levels tracked well with changes in health status over a 3 month period in patients with severe COPD. These data suggest that circulating SPD levels may be useful biomarkers to track health outcomes of COPD patients.     

Do cleaning organisms reduce the stress response of client reef fish?

Background

Marine cleaning interactions in which cleaner fish or shrimps remove parasites from visiting 'client' reef fish are a textbook example of mutualism. However, there is yet no conclusive evidence that cleaning organisms significantly improve the health of their clients. We tested the stress response of wild caught individuals of two client species, Chromis dimidiata and Pseudanthias squamipinnis, that had either access to a cleaner wrasse Labroides dimidiatus, or to cleaner shrimps Stenopus hispidus and Periclimenes longicarpus, or no access to cleaning organisms.

Results

For both client species, we found an association between the presence of cleaner organisms and a reduction in the short term stress response of client fish to capture, transport and one hour confinement in small aquaria, as measured with cortisol levels.

Conclusion

It is conceivable that individuals who are more easily stressed than others pay a fitness cost in the long run. Thus, our data suggest that marine cleaning mutualisms are indeed mutualistic. More generally, measures of stress responses or basal levels may provide a useful tool to assess the impact of interspecific interactions on the partner species.     

Heavy drinking relates to positive valence ratings of alcohol cues

A positive family history of alcohol use disorders (FH) is a robust predictor of personal alcohol abuse and dependence. Exposure to problem-drinking models is one mechanism through which family history influences alcohol-related cognitions and drinking patterns. Similarly, exposure to alcohol advertisements is associated with alcohol involvement and the relationship between affective response to alcohol cues and drinking behavior has not been well established. In addition, the collective contribution that FH, exposure to different types of problem-drinking models (e.g. parents, peers) and personal alcohol use have on appraisal of alcohol-related stimuli has not been evaluated with a large sample. We investigated the independent effects of FH, exposure to problem-drinking models and personal alcohol use on valence ratings of alcohol pictures in a college sample. College students (n = 227) completed measures of personal drinking and substance use, exposure to problem-drinking models, FH and ratings on affective valence of 60 alcohol pictures. Greater exposure to non-familial problem-drinkers predicted greater drinking among college students (beta = 0.17, P < 0.01). However, personal drinking was the only predictor of valence ratings of alcohol pictures (beta = -0.53, P < 0.001). Personal drinking level predicted valence ratings of alcohol cues over and above FH, exposure to problem-drinking models and demographic characteristics. This suggests that positive affective responses to alcohol pictures are more a function of personal experience (i.e. repeated heavy alcohol use) than vicarious learning.