Reduction and Return of Infectious Trachoma in Severely Affected Communities in Ethiopia

Trachoma is one of the leading causes of blindness in the developing world. The World Health Organization has a multi-pronged approach to controlling the ocular chlamydial infection that causes the disease, including distributing antibiotics to entire communities. Even a single community treatment dramatically reduces the prevalence of the infection. Unfortunately, infection returns back into communities after treatment, at least in severely affected areas such as rural Ethiopia. Here, we assess whether additional scheduled treatments in 16 communities in the Gurage area of Ethiopia further reduce infection, and whether the disease returns after distributions are stopped. In communities with the highest levels of trachoma ever studied, we find that repeated mass oral azithromycin distributions gradually reduce the prevalence of trachoma infection in a community, as long as these treatments are given frequently enough and to enough people in the community. Unfortunately, infection returns into the communities after the last treatment. Sustainable changes or complete local elimination of infection will be necessary to stop the return of ocular chlamydial in communities with very high prevalence of the disease

A rationale for continuing mass antibiotic distributions for trachoma

BACKGROUND: The World Health Organization recommends periodic mass antibiotic distributions to reduce the ocular strains of chlamydia that cause trachoma, the world's leading cause of infectious blindness. Their stated goal is to control infection, not to completely eliminate it. A single mass distribution can dramatically reduce the prevalence of infection. However, if infection is not eliminated in every individual in the community, it may gradually return back into the community, so often repeated treatments are necessary. Since public health groups are reluctant to distribute antibiotics indefinitely, we are still in need of a proven long-term rationale. Here we use mathematical models to demonstrate that repeated antibiotic distributions can eliminate infection in a reasonable time period. METHODS: We fit parameters of a stochastic epidemiological transmission model to data collected before and 6 months after a mass antibiotic distribution in a region of Ethiopia that is one of the most severely affected areas in the world. We validate the model by comparing our predicted results to Ethiopian data which was collected biannually for two years past the initial mass antibiotic distribution. We use the model to simulate the effect of different treatment programs in terms of local elimination of infection. RESULTS: Simulations show that the average prevalence of infection across all villages progressively decreases after each treatment, as long as the frequency and coverage of antibiotics are high enough. Infection can be eliminated in more villages with each round of treatment. However, in the communities where infection is not eliminated, it returns to the same average level, forming the same stationary distribution. This phenomenon is also seen in subsequent epidemiological data from Ethiopia. Simulations suggest that a biannual treatment plan implemented for 5 years will lead to elimination in 95% of all villages. CONCLUSION: Local elimination from a community is theoretically possible, even in the most severely infected communities. However, elimination from larger areas may require repeated biannual treatments and prevention of re-introduction from outside to treated areas

The conservation value of human-modified landscapes for the world's primates

Land-use change pushes biodiversity into human-modified landscapes, where native ecosystems are surrounded by anthropic land covers (ALCs). Yet, the ability of species to use these emerging covers remains poorly understood. We quantified the use of ALCs by primates worldwide, and analyzed species' attributes that predict such use. Most species use secondary forests and tree plantations, while only few use human settlements. ALCs are used for foraging by at least 86 species with an important conservation outcome: those that tolerate heavily modified ALCs are 26% more likely to have stable or increasing populations than the global average for all primates. There is no phylogenetic signal in ALCs use. Compared to all primates on Earth, species using ALCs are less often threatened with extinction, but more often diurnal, medium or large-bodied, not strictly arboreal, and habitat generalists. These findings provide valuable quantitative information for improving management practices for primate conservation worldwide

Community Risk Factors for Ocular Chlamydia Infection in Niger: Pre-Treatment Results from a Cluster-Randomized Trachoma Trial

Trachoma is one of the most important neglected tropical diseases because it is the leading cause of blindness from an infection in the world. There are about 1.3 million persons blind from the disease and many more at risk of blindness in the future. It is caused by the common bacterium Chlamydia trachomatis and can be treated with mass drug administrations (MDA) of azithromycin. We have begun a clinical trial in Niger, a country with limited resources in Africa, to determine the best treatment strategy. Our study from May to July 2010, which began before MDA's were given, showed that 26% of children aged 0–5 years were infected with the disease. In these children, we found that discharge from the nose, presence of flies on the face, and the number of years of education completed by the head of the household were risk factors for infection in 48 different communities. We hope to use this information about risk factors of infection to help guide future studies for trachoma and also to help with the WHO goal of eliminating the disease worldwide by the year 2020

Peptidoglycan-Modifying Enzyme Pgp1 Is Required for Helical Cell Shape and Pathogenicity Traits in Campylobacter jejuni

The impact of bacterial morphology on virulence and transmission attributes of pathogens is poorly understood. The prevalent enteric pathogen Campylobacter jejuni displays a helical shape postulated as important for colonization and host interactions. However, this had not previously been demonstrated experimentally. C. jejuni is thus a good organism for exploring the role of factors modulating helical morphology on pathogenesis. We identified an uncharacterized gene, designated pgp1 (peptidoglycan peptidase 1), in a calcofluor white-based screen to explore cell envelope properties important for C. jejuni virulence and stress survival. Bioinformatics showed that Pgp1 is conserved primarily in curved and helical bacteria. Deletion of pgp1 resulted in a striking, rod-shaped morphology, making pgp1 the first C. jejuni gene shown to be involved in maintenance of C. jejuni cell shape. Pgp1 contributes to key pathogenic and cell envelope phenotypes. In comparison to wild type, the rod-shaped pgp1 mutant was deficient in chick colonization by over three orders of magnitude and elicited enhanced secretion of the chemokine IL-8 in epithelial cell infections. Both the pgp1 mutant and a pgp1 overexpressing strain – which similarly produced straight or kinked cells – exhibited biofilm and motility defects. Detailed peptidoglycan analyses via HPLC and mass spectrometry, as well as Pgp1 enzyme assays, confirmed Pgp1 as a novel peptidoglycan DL-carboxypeptidase cleaving monomeric tripeptides to dipeptides. Peptidoglycan from the pgp1 mutant activated the host cell receptor Nod1 to a greater extent than did that of wild type. This work provides the first link between a C. jejuni gene and morphology, peptidoglycan biosynthesis, and key host- and transmission-related characteristics

Regional cortical volumes and congenital heart disease: a MRI study in 22q11.2 deletion syndrome

Children with congenital heart disease (CHD) who survive surgery often present impaired neurodevelopment and qualitative brain anomalies. However, the impact of CHD on total or regional brain volumes only received little attention. We address this question in a sample of patients with 22q11.2 deletion syndrome (22q11DS), a neurogenetic condition frequently associated with CHD. Sixty-one children, adolescents, and young adults with confirmed 22q11.2 deletion were included, as well as 80 healthy participants matched for age and gender. Subsequent subdivision of the patients group according to CHD yielded a subgroup of 27 patients with normal cardiac status and a subgroup of 26 patients who underwent cardiac surgery during their first years of life (eight patients with unclear status were excluded). Regional cortical volumes were extracted using an automated method and the association between regional cortical volumes, and CHD was examined within a three-condition fixed factor. Robust protection against type I error used Bonferroni correction. Smaller total cerebral volumes were observed in patients with CHD compared to both patients without CHD and controls. The pattern of bilateral regional reductions associated with CHD encompassed the superior parietal region, the precuneus, the fusiform gyrus, and the anterior cingulate cortex. Within patients, a significant reduction in the left parahippocampal, the right middle temporal, and the left superior frontal gyri was associated with CHD. The present results of global and regional volumetric reductions suggest a role for disturbed hemodynamic in the pathophysiology of brain alterations in patients with neurodevelopmental disease and cardiac malformations

Pneumocystis murina colonization in immunocompetent surfactant protein A deficient mice following environmental exposure

<p>Abstract</p> <p>Background</p> <p><it>Pneumocystis spp</it>. are opportunistic pathogens that cause pneumonia in immunocompromised humans and animals. <it>Pneumocystis </it>colonization has also been detected in immunocompetent hosts and may exacerbate other pulmonary diseases. Surfactant protein A (SP-A) is an innate host defense molecule and plays a role in the host response to <it>Pneumocystis</it>.</p> <p>Methods</p> <p>To analyze the role of SP-A in protecting the immunocompetent host from <it>Pneumocystis </it>colonization, the susceptibility of immunocompetent mice deficient in SP-A (KO) and wild-type (WT) mice to <it>P. murina </it>colonization was analyzed by reverse-transcriptase quantitative PCR (qPCR) and serum antibodies were measured by enzyme-linked immunosorbent assay (ELISA).</p> <p>Results</p> <p>Detection of <it>P. murina </it>specific serum antibodies in immunocompetent WT and KO mice indicated that the both strains of mice had been exposed to <it>P. murina </it>within the animal facility. However, P. <it>murina </it>mRNA was only detected by qPCR in the lungs of the KO mice. The incidence and level of the mRNA expression peaked at 8–10 weeks and declined to undetectable levels by 16–18 weeks. When the mice were immunosuppressed, <it>P. murina </it>cyst forms were also only detected in KO mice. <it>P. murina </it>mRNA was detected in <it>SCID </it>mice that had been exposed to KO mice, demonstrating that the immunocompetent KO mice are capable of transmitting the infection to immunodeficient mice. The pulmonary cellular response appeared to be responsible for the clearance of the colonization. More CD4+ and CD8+ T-cells were recovered from the lungs of immunocompetent KO mice than from WT mice, and the colonization in KO mice depleted CD4+ cells was not cleared.</p> <p>Conclusion</p> <p>These data support an important role for SP-A in protecting the immunocompetent host from <it>P. murina </it>colonization, and provide a model to study <it>Pneumocystis </it>colonization acquired via environmental exposure in humans. The results also illustrate the difficulties in keeping mice from exposure to <it>P. murina </it>even when housed under barrier conditions.</p

ICAR: endoscopic skull‐base surgery

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Glucose and norepinephrine challenges during abomasal infusion of cis or trans octadecenoates in Holstein cows

This experiment determined the effects of infusion of mixtures of fat containing predominantly cis-C-18:1 or trans-C-18:1 fatty acids into the abomasum on responses of cows to glucose and norepinephrine challenges administered i.v. Six lactating Holstein cows, each with a rumen cannula, were arranged in two Latin squares with 21-d periods. The common basal diet contained 40% forage and 60% concentrate. Treatments were the uninfused control, 750 g/d of a cis fat mixture (65% high oleic sunflower oil and 35% cocoa butter), and 750 g/d of a trans fat mixture (93% shortening and 7% corn oil) infused into the abomasum via a tube that passed through the rumen cannula. Glucose challenges (0.4 mg/kg of BW, administered i.v.) were conducted on d 18, and norepinephrine challenges (0.7 mu g/kg of BW, administered i.v.) were conducted on d 19 of each experimental period. Despite a lower percentage of fat in milk for trans than for cis treatment, disappearance rates of glucose, secretion of insulin after glucose challenge, and appearance rates of NEFA and triglycerides after norepinephrine challenge mere similar between treatments. Thus, these data support the hypothesis that trans-C-18:1 fatty acids affect the synthesis of milk fat in the mammary gland of lactating cows