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Introduction: Respondent-driven sampling (RDS) offers a recruitment strategy for hard-to-reach populations. However, RDS faces logistical and theoretical challenges that threaten efficiency and validity in settings worldwide. We present innovative adaptations to conventional RDS to overcome barriers encountered in recruiting a large, representative sample of men who have sex with men (MSM) who travel internationally. Methods: Novel methodological adaptations for the “International Travel Research to Inform Prevention” or “I-TRIP” study were offering participants a choice between electronic and paper coupons referrals for recruitment and modifying the secondary incentives structure from small cash amounts to raffle entries for periodic large cash prize raffle drawings. Staged referral limit increases from 3 to 10 referrals and progressive addition of 70 seeds were also implemented. Results: There were 501 participants enrolled in up to 13 waves of growth. Among participants with a choice of referral methods, 81% selected electronic referrals. Of participants who were recruited electronically, 90% chose to remain with electronic referrals when it was their turn to recruit. The mean number of enrolled referrals was 0.91 for electronic referrals compared to 0.56 for paper coupons. Median referral lag time, i.e., the time interval between when recruiters were given their referrals and when a referred individual enrolled in the study, was 20 days (IQR 10–40) for electronic referrals, 20 days (IQR 8–58) for paper coupons, 20 days (IQR 10–41) for raffle entries and 33 days (IQR 16–148) for small cash incentives. Conclusions: The recruitment of MSM who travel internationally required maximizing known flexible tools of RDS while at the same time necessitating innovations to increase recruitment efficiency. Electronic referrals emerged as a major advantage in recruiting this hard-to-reach population who are of high socio-economic status, geographically diffuse and highly mobile. These enhancements may improve the performance of RDS in target populations with similar characteristics. [ABSTRACT FROM AUTHOR]

Background: Around 67 million pets are owned by households in the United Kingdom, and an increasing number of these are exotic animals. Approximately a third of pets are purchased through retail outlets or direct from breeders. A wide range of infections can be associated with companion animals. Objectives: This study uses a systematic literature review to describe the transmission of zoonotic disease in humans associated with a pet shop or other location selling pets (incidents of rabies tracebacks and zoonoses from pet food were excluded). Data sources: PubMed and EMBASE. Results: Fifty seven separate case reports or incidents were described in the 82 papers that were identified by the systematic review. Summary information on each incident is included in this manuscript. The infections include bacterial, viral and fungal diseases and range in severity from mild to life threatening. Infections associated with birds and rodents were the most commonly reported. Over half of the reports describe incidents in the Americas, and three of these were outbreaks involving more than 50 cases. Many of the incidents identified relate to infections in pet shop employees. Limitations: This review may have been subject to publication bias, where unusual and unexpected zoonotic infections may be over-represented in peer-reviewed publications. It was also restricted to English-language articles so that pathogens that are more common in non-Western countries, or in more exotic animals not common in Europe and the Americas, may have been under-represented. Conclusions/implications: A wide spectrum of zoonotic infections are acquired from pet shops. Salmonellosis and psittacosis were the most commonly documented diseases, however more unusual infections such as tularemia also appeared in the review. Given their potential to spread zoonotic infection, it is important that pet shops act to minimise the risk as far as possible. [ABSTRACT FROM AUTHOR]

The techniques used for diagnosis of canine visceral leishmaniasis (CVL) in Brazil ELISA and IFAT have been extensively questioned because of the accuracy of these tests. A recent change in the diagnosis protocol excluded IFAT and included the Dual-Path Platform (DPP). We evaluated the prevalence and incidence rates of Leishmania spp. before and after the change in the protocol. In addition, based on our results, we propose a new alternative that is less expensive for the screening and confirmation of CVL. Plasma samples were obtained from a serobank from dogs evaluated in a cross-sectional study (1,226 dogs) and in a cohort study of susceptible animals (n = 447), followed for 26 months. Serology testing was performed using ELISA, IFAT, and DPP. The incidence and prevalence of CVL were determined by using the protocol of the Visceral Leishmaniasis Control and Surveillance Program until 2012 (ELISA and IFAT using filter paper) and the protocol used after 2012 (DPP and ELISA using plasma). The prevalence was 6.2% and the incidence was 2.8 per 1,000 dog-months for the protocol used until 2012. For the new diagnosis protocol for CVL resulted in an incidence of 5.4 per 1,000 dog-months and a prevalence of 8.1%. Our results showed that the prevalence and incidence of infection were far greater than suggested by the previously used protocol and that the magnitude of infection in endemic areas has been underestimated. As tests are performed sequentially and euthanasia of dogs is carried out when the serological results are positive in both tests, the sequence does not affect the number of animals to be eliminated by the Control Program. Then we suggest to municipalities with a large demand of exams to use ELISA for screening and DPP for confirmation, since this allows easier performance and reduced cost. [ABSTRACT FROM AUTHOR]

We report on the accuracy of using near-infrared spectroscopy (NIRS) to predict the age of Anopheles mosquitoes reared from wild larvae and a mixed age-wild adult population collected from pit traps after exposure to pyrethroids. The mosquitoes reared from wild larvae were estimated as <7 or ≥7 d old with an overall accuracy of 79%. The age categories of Anopheles mosquitoes that were not exposed to the insecticide papers were predicted with 78% accuracy whereas the age categories of resistant, susceptible and mosquitoes exposed to control papers were predicted with 82%, 78% and 79% accuracy, respectively. The ages of 85% of the wild-collected mixed-age Anopheles were predicted by NIRS as ≤8 d for both susceptible and resistant groups. The age structure of wild-collected mosquitoes was not significantly different for the pyrethroid-susceptible and pyrethroid-resistant mosquitoes (P = 0.210). Based on these findings, NIRS chronological age estimation technique for Anopheles mosquitoes may be independent of insecticide exposure and the environmental conditions to which the mosquitoes are exposed. [ABSTRACT FROM AUTHOR]

Plasma sterilization offers a faster, less toxic and versatile alternative to conventional sterilization methods. Using a relatively small, low temperature, atmospheric, dielectric barrier discharge surface plasma generator, we achieved ≥6 log reduction in concentration of vegetative bacterial and yeast cells within 4 minutes and ≥6 log reduction of Geobacillus stearothermophilus spores within 20 minutes. Plasma sterilization is influenced by a wide variety of factors. Two factors studied in this particular paper are the effect of using different dielectric substrates and the significance of the amount of liquid on the dielectric surface. Of the two dielectric substrates tested (FR4 and semi-ceramic (SC)), it is noted that the FR4 is more efficient in terms of time taken for complete inactivation. FR4 is more efficient at generating plasma as shown by the intensity of spectral peaks, amount of ozone generated, the power used and the speed of killing vegetative cells. The surface temperature during plasma generation is also higher in the case of FR4. An inoculated FR4 or SC device produces less ozone than the respective clean devices. Temperature studies show that the surface temperatures reached during plasma generation are in the range of 30°C–66°C (for FR4) and 20°C–49°C (for SC). Surface temperatures during plasma generation of inoculated devices are lower than the corresponding temperatures of clean devices. pH studies indicate a slight reduction in pH value due to plasma generation, which implies that while temperature and acidification may play a minor role in DBD plasma sterilization, the presence of the liquid on the dielectric surface hampers sterilization and as the liquid evaporates, sterilization improves. [ABSTRACT FROM AUTHOR]

Background: Dried blood spots (DBS) have been used as alternative specimens to plasma to increase access to HIV viral load (VL) monitoring and early infant diagnosis (EID) in remote settings. We systematically reviewed evidence on the performance of DBS compared to plasma for VL monitoring and EID. Methods and Findings: Thirteen peer reviewed HIV VL publications and five HIV EID papers were included. Depending on the technology and the viral load distribution in the study population, the percentage of DBS samples that are within 0.5 log of VL in plasma ranged from 52–100%. Because the input sample volume is much smaller in a blood spot, there is a risk of false negatives with DBS. Sensitivity of DBS VL was found to be 78–100% compared to plasma at VL below 1000 copies/ml, but this increased to 100% at a threshold of 5000 copies/ml. Unlike a plasma VL test which measures only cell free HIV RNA, a DBS VL also measures proviral DNA as well as cell-associated RNA, potentially leading to false positive results when using DBS. The systematic review showed that specificity was close to 100% at DBS VL above 5000 copies/ml, and this threshold would be the most reliable for predicting true virologic failure using DBS. For early infant diagnosis, DBS has a sensitivity of 100% compared to fresh whole blood or plasma in all studies. Conclusions: Although limited data are available for EID, DBS offer a highly sensitive and specific sampling strategy to make viral load monitoring and early infant diagnosis more accessible in remote settings. A standardized approach for sampling, storing, and processing DBS samples would be essential to allow successful implementation. Trial Registration: PROSPERO Registration #: CRD42013003621. [ABSTRACT FROM AUTHOR]

Introduction: Role of vaginal sex in heterosexual transmission of HIV has been investigated but that of heterosexual anal sex (HAS) is not fully understood. This paper examines practice of HAS among Female Sex Workers (FSWs) and its correlates in India where the HIV epidemic is being primarily driven by core groups like FSWs. Methods: Data for this paper are drawn from Round I survey of 9667 FSWs in the Integrated Biological and Behavioral Assessment (IBBA) from 23 districts of 4 high HIV prevalent states of India. Bivariate and multivariate analysis identified factors associated with HAS. Results: Ever having anal sex was reported by 11.9% FSWs (95% CI: 11.3%–12.6%). Typology (AOR 2.20, 95% CI 1.64–2.95) and literacy (AOR 1.28, 95% CI 1.10–1.49) were positively associated with practice of HAS. Longer duration in sex trade (AOR 1.69, 95% CI 1.44–1.99), entertaining larger number of clients the previous week (AOR 1.78, 95% CI 1.47–2.15), alcohol consumption (AOR 1.21, 95% CI 1.03–1.42) and inability to negotiate condom use (AOR 1.53, 95% CI 1.28–1.83) were also correlated with HAS. Self-risk perception for HIV (AOR 1.46, 95% CI 1.25–1.71) did not impede HAS. Although symptoms of sexually transmitted infections (STIs) in the last 12 months were associated with anal sex (AOR 1.39, 95% CI 1.13–1.72) there was no significant association between laboratory confirmed HIV and other STIs with HAS. Conclusion: Practice of HAS by FSWs might significantly contribute to HIV transmission in India. This study also shows that despite self-risk perception for HIV, even literate FSWs with longer duration in sex work report HAS. General messages on condom use may not influence safe HAS. FSWs need to be targeted with specific messages on HIV transmission during anal sex. Women controlled prevention methods, such as rectal microbicides and vaginal microbicides are needed. [ABSTRACT FROM AUTHOR]

Bacterial polysaccharides have numerous clinical or industrial uses. Recombinant plants could offer the possibility of producing bacterial polysaccharides on a large scale and free of contaminating bacterial toxins and antigens. We investigated the feasibility of this proposal by cloning and expressing the gene for the type 3 synthase (cps3S) of Streptococcus pneumoniae in Nicotinia tabacum, using the pCambia2301 vector and Agrobacterium tumefaciens-mediated gene transfer. In planta the recombinant synthase polymerised plant-derived UDP-glucose and UDP-glucuronic acid to form type 3 polysaccharide. Expression of the cps3S gene was detected by RT-PCR and production of the pneumococcal polysaccharide was detected in tobacco leaf extracts by double immunodiffusion, Western blotting and high-voltage paper electrophoresis. Because it is used a component of anti-pneumococcal vaccines, the immunogenicity of the plant-derived type 3 polysaccharide was tested. Mice immunised with extracts from recombinant plants were protected from challenge with a lethal dose of pneumococci in a model of pneumonia and the immunised mice had significantly elevated levels of serum anti-pneumococcal polysaccharide antibodies. This study provides the proof of the principle that bacterial polysaccharide can be successfully synthesised in plants and that these recombinant polysaccharides could be used as vaccines to protect against life-threatening infections. [ABSTRACT FROM AUTHOR]

Background: More than two-thirds of the world's HIV-positive individuals live in sub-Saharan Africa, where genetic susceptibility to kidney disease is high and resources for kidney disease screening and antiretroviral therapy (ART) toxicity monitoring are limited. Equations to estimate glomerular filtration rate (GFR) from serum creatinine were derived in Western populations and may be less accurate in this population. Methods: We compared results from published GFR estimating equations with a direct measure of GFR by iohexol clearance in 99 HIV-infected, ART-naïve Kenyan adults. Iohexol concentration was measured from dried blood spots on filter paper. The bias ratio (mean of the ratio of estimated to measured GFR) and accuracy (percentage of estimates within 30% of the measured GFR) were calculated. Results: The median age was 35 years, and 60% were women. The majority had asymptomatic HIV, with median CD4+ cell count of 355 cells/mm3. Median measured GFR was 115 mL/min/1.73 m2. Overall accuracy was highest for the Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equation. Consistent with a prior report, bias and accuracy were improved by eliminating the coefficient for black race (85% of estimates within 30% of measured GFR). Accuracy of all equations was poor in participants with GFR 60–90 mL/min/1.73 m2 (<65% of estimates within 30% of measured GFR), although this subgroup was too small to reach definitive conclusions. Conclusions: Overall accuracy was highest for the CKD-EPI equation. Eliminating the coefficient for race further improved performance. Future studies are needed to determine the most accurate GFR estimate for use in individuals with GFR <90 mL/min/1.73 m2, in whom accurate estimation of kidney function is important to guide drug dosing. Direct measurement of GFR by iohexol clearance using a filter paper based assay is feasible for research purposes in resource-limited settings, and could be used to develop more accurate GFR estimates in African populations. [ABSTRACT FROM AUTHOR]

Background: Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases. Methods and Findings: For each disease, we performed a systematic search with no restriction on date or language of publication on Medline, Web of Knowledge, Cochrane CENTRAL and SCOPUS up to December 2010 to identify systematic reviews of public health interventions. We retrieved some 3176 records of which 85 full papers were assessed and 33 included in the review. The included papers investigated the effect of public health interventions on various outcome measures. All interventions were GRADE assessed to determine the strength of evidence. In addition we developed a systematic review quality score. The interventions included environmental interventions to control vectors, chemoprophylaxis, immunization, household and community water treatment, greening cities and community advice. For most reviews, GRADE showed low quality of evidence because of poor study design and high heterogeneity. Also for some key areas such as floods, droughts and other weather extremes, there are no adequate systematic reviews of potential public health interventions. Conclusion: In conclusion, we found the evidence base to be mostly weak for environmental interventions that could have the most value in a warmer world. Nevertheless, such interventions should not be dismissed. Future research on public health interventions for climate change adaptation needs to be concerned about quality in study design and should address the gap for floods, droughts and other extreme weather events that pose a risk to health. [ABSTRACT FROM AUTHOR]

Background & Aims: Dried blood spots (DBS) on filter paper have been successfully used to diagnose and monitor several infectious diseases. The aim was to investigate the performance of DBS in hepatitis B virus (HBV) diagnosis using commercial tests in comparison to standard methods. Methods: Paired DBS and plasma samples were collected from 200 patients: 100 patients with HBsAg negative status and 100 patients with HBsAg positive status. In the latter patient, HBeAg reactivity was tested. Ten samples of anti-HBs were collected from people vaccinated against HBV. We also studied 50 patients with positive HBV DNA viral load in plasma and 10 HBV DNA negative patients. HBV genotypes and gene polymerase mutations were determined in 10 randomly selected HBV-infected patients. The DBS sample consisted of 50 µL of whole blood, i.e. a 12-mm paper card. Results: The sensitivity thresholds of HBsAg and anti-HBs antibody were 0.30±0.08 IU/mL and 18.11±6.05 IU/mL, respectively, for DBS with 98% sensitivity and 100% specificity. Sensitivity was 98% and specificity 100% for the detection of HBV DNA on a blotter, considering an HBV DNA threshold of 914.1±157.8 IU/ml. Ten patients had an HBeAg positive status in plasma, all were detected positive using DBS. HBV genotyping and mutation detection were successfully performed on DBS, with full concordance between the 10 paired DBS and plasma samples. Conclusion: This study shows DBS is a reliable alternative to plasma specimens for quantifying and detecting HBsAg, anti-HBs, HBeAg and genotyping. DBS may increase the opportunities for HBV testing and treatment follow-up in hard-to-reach individuals. [ABSTRACT FROM AUTHOR]

To date, vaccination is the most cost-effective strategy to combat infectious diseases. Recently, a productivity gap affects the pharmaceutical industry. The productivity gap describes the situation whereby the invested resources within an industry do not match the expected product turn-over. While risk profiles (combining research and development timelines and transition rates) have been published for new chemical entities (NCE), little is documented on vaccine development. The objective is to calculate risk profiles for vaccines targeting human infectious diseases. A database was actively compiled to include all vaccine projects in development from 1998 to 2009 in the pre-clinical development phase, clinical trials phase I, II and III up to Market Registration. The average vaccine, taken from the preclinical phase, requires a development timeline of 10.71 years and has a market entry probability of 6%. Stratification by disease area reveals pandemic influenza vaccine targets as lucrative. Furthermore, vaccines targeting acute infectious diseases and prophylactic vaccines have shown to have a lower risk profile when compared to vaccines targeting chronic infections and therapeutic applications. In conclusion; these statistics apply to vaccines targeting human infectious diseases. Vaccines targeting cancer, allergy and autoimmune diseases require further analysis. Additionally, this paper does not address orphan vaccines targeting unmet medical needs, whether projects are in-licensed or self-originated and firm size and experience. Therefore, it remains to be investigated how these - and other - variables influence the vaccine risk profile. Although we find huge differences between the risk profiles for vaccine and NCE; vaccines outperform NCE when it comes to development timelines. [ABSTRACT FROM AUTHOR]

Background: A large proportion of patients receiving antiretroviral therapy (ART) in low and middle income countries (LMICs) have unknown treatment outcomes and are classified as lost to follow-up (LTFU). Physical tracing of patients classified as LTFU is common; however, effects of tracing on outcomes remains unclear. The objective of this systematic review is to compare estimates of LTFU, mortality and retention in LMIC in cohorts of patients with and without physical tracing. Methods and Findings: We systematically identified studies in LMIC programmatic settings using MEDLINE (2003–2011) and HIV conference abstracts (2009–2011). Studies reporting the proportion LTFU 12-months after ART initiation were included. Tracing activities were determined from manuscripts or by contacting study authors. Studies were classified as “tracing studies” if physical tracing was available for the majority of patients. Summary estimates from the 2 groups of studies (tracing and non-tracing) for LTFU, mortality, stop of ART, transfers out, and retention on ART were determined. 261 papers and 616 abstracts were identified of which 39 studies comprising 54 separate cohorts (n = 187,666) met inclusion criteria. Of those, physical tracing was available for 46% of cohorts. Treatment programs with physical tracing activities had lower estimated LTFU (7.6% vs. 15.1%; p<.001), higher estimated mortality (10.5% vs. 6.6%; p = .006), higher retention on ART (80.0 vs. 75.8%; p = .04) and higher retention at the original site (80.0% vs. 72.9%; p = .02). Conclusions: Knowledge of patient tracing is critical when interpreting program outcomes of LTFU, mortality and retention. The reduction of the proportion LTFU in tracing studies was only partially explained by re-classification of unknown outcomes. These data suggest that tracing may lead to increased re-engagement of patients in care, rather than just improved classification of unknown outcomes. [ABSTRACT FROM AUTHOR]

This paper explored our hypothesis that sRNA (18∼30 bp) deep sequencing technique can be used as an efficient strategy to identify microorganisms other than viruses, such as prokaryotic and eukaryotic pathogens. In the study, the clean reads derived from the sRNA deep sequencing data of wild-caught ticks and mosquitoes were compared against the NCBI nucleotide collection (non-redundant nt database) using Blastn. The blast results were then analyzed with in-house Python scripts. An empirical formula was proposed to identify the putative pathogens. Results showed that not only viruses but also prokaryotic and eukaryotic species of interest can be screened out and were subsequently confirmed with experiments. Specially, a novel Rickettsia spp. was indicated to exist in Haemaphysalis longicornis ticks collected in Beijing. Our study demonstrated the reuse of sRNA deep sequencing data would have the potential to trace the origin of pathogens or discover novel agents of emerging/re-emerging infectious diseases. [ABSTRACT FROM AUTHOR]

Leishmaniasis remains one of the world's most devastating neglected tropical diseases. It mainly affects developing countries, where it often co-exists with chronic malnutrition, one of the main risk factors for developing the disease. Few studies have been published, however, on the relationship between leishmaniasis progression and malnutrition. The present paper reports the influence of protein malnutrition on the immune response and visceral disease development in adult hamsters infected with Leishmania infantum fed either standard or low protein diets. The low protein diet induced severe malnutrition in these animals, and upon infection with L. infantum 33% had severe visceral leishmaniasis compared to only 8% of animals fed the standard diet. The infected, malnourished animals showed notable leukocyte depletion, mild specific antibody responses, impairment of lymphoproliferation, presence of parasites in blood (16.67% of the hamsters) and significant increase of the splenic parasite burden. Animals fed standard diet suffered agranulocytosis and monocytopenia, but showed stronger specific immune responses and had lower parasite loads than their malnourished counterparts. The present results show that protein malnutrition promotes visceral leishmaniasis and provide clues regarding the mechanisms underlying the impairment of the immune system. [ABSTRACT FROM AUTHOR]

Objective: This paper describes the physical structure and environmental contamination in selected hospital wards in three government hospitals in Bangladesh. Methods: The qualitative research team conducted 48 hours of observation in six wards from three Bangladeshi tertiary hospitals in 2007. They recorded environmental contamination with body secretions and excretions and medical waste and observed ward occupant handwashing and use of personal protective equipment. They recorded number of persons, number of open doors and windows, and use of fans. They measured the ward area and informally observed waste disposal outside the wards. They conducted nine focus group discussions with doctors, nurses and support staff. Results: A median of 3.7 persons were present per 10 m2 of floor space in the wards. A median of 4.9 uncovered coughs or sneezes were recorded per 10 m2 per hour per ward. Floors in the wards were soiled with saliva, spit, mucous, vomitus, feces and blood 125 times in 48 hours. Only two of the 12 patient handwashing stations had running water and none had soap. No disinfection was observed before or after using medical instruments. Used medical supplies were often discarded in open containers under the beds. Handwashing with soap was observed in only 32 of 3,373 handwashing opportunities noted during 48 hours. Mosquitoes and feral cats were commonly observed in the wards. Conclusions: The physical structure and environment of our study hospitals are conducive to the spread of infection to people in the wards. Low-cost interventions on hand hygiene and cleaning procedures for rooms and medical equipment should be developed and evaluated for their practicality and effectiveness. [ABSTRACT FROM AUTHOR]

Multi-drug resistant tuberculosis (MDR-TB) represents a threat to health and development in countries with high TB burden. China’s MDR-TB prevalence rate of 6.8% is the highest in the world. Interventions to remove barriers against effective TB control, and prevention of MDR-TB are urgently needed in the country. This paper reports a cross-sectional questionnaire survey of 513 pulmonary TB (PTB) patients, and qualitative interviews of 10 healthcare workers (HCWs), and 15 PTB patients. The objective was to assess barriers against effective control of PTB and prevention of MDR-TB by elucidating the perspectives of patients and healthcare providers. Results showed that more than half of the patients experienced patient delay of over 12.5 days. A similar proportion also experienced detection delay of over 30 days, and delay in initiating treatment of over 31 days. Consulting a non-TB health facility ≥3 times before seeking care at TB dispensary was a risk factor for both detection delay [AOR (95% CI): 1.89(1.07, 3.34) and delay in initiating treatment[AOR (95% CI): 1.88 (1.06, 3.36). Results revealed poor implementation of Directly Observed Therapy (DOT), whereby treatment of 34.3% patients was never monitored by HCWs. Only 31.8% patients had ever accessed TB health education before their TB diagnosis. Qualitative data consistently disclosed long patient delay, and indicated that patient’s poor TB knowledge and socioeconomic barriers were primary reasons for patient delay. Seeking care and being treated at a non-TB hospital was an important reason for detection delay. Patient’s long work hours and low income increased risk for treatment non-adherence. Evidence-based measures to improve TB health seeking behavior, reduce patient and detection delays, improve the quality of DOT, address financial and system barriers, and increase access to TB health promotion are urgently needed to address the burgeoning prevalence of MDR-TB in China. [ABSTRACT FROM AUTHOR]

Public health surveillance systems provide valuable data for reliable predication of future epidemic events. This paper describes a study that used nine types of infectious disease data collected through a national public health surveillance system in mainland China to evaluate and compare the performances of four time series methods, namely, two decomposition methods (regression and exponential smoothing), autoregressive integrated moving average (ARIMA) and support vector machine (SVM). The data obtained from 2005 to 2011 and in 2012 were used as modeling and forecasting samples, respectively. The performances were evaluated based on three metrics: mean absolute error (MAE), mean absolute percentage error (MAPE), and mean square error (MSE). The accuracy of the statistical models in forecasting future epidemic disease proved their effectiveness in epidemiological surveillance. Although the comparisons found that no single method is completely superior to the others, the present study indeed highlighted that the SVMs outperforms the ARIMA model and decomposition methods in most cases. [ABSTRACT FROM AUTHOR]

Bacteria of the family Rickettsiaceae have always been largely studied not only for their importance in the medical field, but also as model systems in evolutionary biology. In fact, they share a recent common ancestor with mitochondria. The most studied species, belonging to genera Rickettsia and Orientia, are hosted by terrestrial arthropods and include many human pathogens. Nevertheless, recent findings show that a large part of Rickettsiaceae biodiversity actually resides outside the group of well-known pathogenic bacteria. Collecting data on these recently described non-conventional members of the family is crucial in order to gain information on ancestral features of the whole group. Although bacteria of the family Rickettsiaceae, and of the whole order Rickettsiales, are formally described as non-flagellated prokaryotes, some recent findings renewed the debate about this feature. In this paper we report the first finding of members of the family displaying numerous flagella and active movement inside their host cells. These two new taxa are hosted in aquatic environments by protist ciliates and are described here by means of ultrastructural and molecular characterization. Data here reported suggest that the ancestor of Rickettsiales displayed flagellar movement and re-evaluate the hypothesis that motility played a key-role in the origin of mitochondria. Moreover, our study highlights that the aquatic environment represents a well exploited habitat for bacteria of the family Rickettsiaceae. Our results encourage a deep re-consideration of ecological and morphological traits of the family and of the whole order. [ABSTRACT FROM AUTHOR]

The Rhodnius Pacific group is composed of three species: Rhodnius pallescens, R. colombiensis and R. ecuadoriensis, which are considered important vectors of trypanosomes (Trypanosoma cruzi and T. rangeli) infecting humans. This group is considered as a recent trans-Andean lineage derived from the widespread distributed sister taxa R. pictipes during the later uplift of northern Andes mountain range. The widest spread species R. pallescens may be a complex of two divergent lineages with different chromosomal attributes and a particular biogeographical distribution across Central America and Colombia with several southern populations in Colombia occupying the same sylvatic habitat as its sister species R. colombiensis. Although the taxonomy of Rhodnius Pacific group has been well studied, the unresolved phylogenetic and systematic issues are the target of this paper. Here we explore the molecular phylogeography of this species group analyzing two mitochondrial (ND4 and cyt b) and one nuclear (D2 region of ribosomal 28S gene) gene sequences. The molecular analyses suggest an early divergence of the species R. ecuadoriensis and R. colombiensis, followed by a recent expansion of R. pallescens lineages. The phylogenetic relationship between sympatric R. pallescens Colombian lineage and R. colombiensis was further explored using wing morphometry, DNA genome size measurements, and by analyzing chromosomal behavior of hybrids progeny obtained from experimental crosses. Our results suggest that the diversification of the two R. pallescens lineages was mainly influenced by biogeographical events such as (i) the emergence of the Panama Isthmus, while the origin and divergence of R. colombiensis was associated with (ii) the development of particular genetic and chromosomal features that act as isolation mechanisms from its sister species R. pallescens (Colombian lineage). These findings provide new insights into the evolution of the Rhodnius Pacific group and the underlying biological processes that occurred during its divergence. [ABSTRACT FROM AUTHOR]

Background: Since launching of antiretroviral (ART) treatment, the numbers of patients enrolled in to ART are increasing in many developing countries. But many studies done across Africa including Ethiopia on antiretroviral therapy programs have shown higher mortality at the first six months of treatment initiation. But the factors associated with this high mortality are poorly characterized. So this study aims to determine mortality and identify predictors of it among patients on ART. Methods: Retrospective cohort study was employed among a total of 520 records of patients who were enrolled on antiretroviral therapy in Aksum hospital from September 2006 to August 2011. Baseline patient records were extracted from electronic and paper based medical records database and analysed using Kaplan Meier survival and Cox proportional hazard model to identify the independent predictors of mortality of patients on ART. Results: A total of 46 (8.85%) deaths was observed giving an overall mortality rate of 3.2 per 100 person-years. The independent predictor of mortality identified for this cohort were haemoglobin level <11 mg/dl (Hazard Ratio (HR) = 1.9, 95%-CI = 1.01, 3.52), CD4 cell counts lower than 50 cells/µl (HR = 2.1, 95%- CI = 1.13,3.89), Male gender (HR = 1.9, 95%-CI = 1.01,3.52), Weight <40 kg (HR = 2.3,95% CI = 1.24,4.55), primary level of education and lower (HR = 2.6, 95%- CI = 1.29,5.55). Conclusions: The over all mortality of adults patients on ART was low but higher in the early months of ART initiation. low levels of haemoglobin <11 gm/dl, lower CD4 cell count, male gender, weight <40 Kg and individuals who have primary level of education and lower were indentified as the independent predictors of mortality. For this reason, early initiation of ART despite the CD4 count and method of HIV diagnosis, nutritional support and close monitoring of patients in the early periods of ART treatment initiation is very crucial to improve patient survival. [ABSTRACT FROM AUTHOR]

People with TB and/or HIV frequently experience severe economic barriers to health care, including out-of-pocket expenses related to diagnosis and treatment, as well as indirect costs due to loss of income. These barriers can both aggravate economic hardship and prevent or delay diagnosis, treatment and successful outcome, leading to increased transmission, morbidity and mortality. WHO, UNAIDS and the ILO argue that economic support of various kinds is essential to enable vulnerable people to protect themselves from infection, avoid delayed diagnosis and treatment, overcome barriers to adherence, and avert destitution. This paper analyses successful country proposals to the Global Fund to Fight AIDS, Tuberculosis and Malaria that include economic support in Rounds 7 and 10; 36 and 20 HIV and TB grants in Round 7 and 32 and 26, respectively, in Round 10. Of these, up to 84 percent included direct or indirect economic support for beneficiaries, although the amount constituted a very small proportion of the total grant. In TB grants, the objectives of economic support were generally clearly stated, and focused on mechanisms to improve treatment uptake and adherence, and the case was most clearly made for MDR-TB patients. In HIV grants, the objectives were much broader in scope, including mitigation of adverse economic and social effects of HIV and its treatment on both patients and families. The analysis shows that economic support is on the radar for countries developing Global Fund proposals, and a wide range of economic support activities are in place. In order to move forward in this area, the wealth of country experience that exists needs to be collated, assessed and disseminated. In addition to trials, operational research and programme evaluations, more precise guidance to countries is needed to inform evidence-based decision about activities that are cost-effective, affordable and feasible. [ABSTRACT FROM AUTHOR]

No matching vaccine is immediately available when a novel influenza strain breaks out. Several nonvaccine-related strategies must be employed to control an influenza epidemic, including antiviral treatment, patient isolation, and immigration detection. This paper presents the development and application of two regional dynamic models of influenza with Pontryagin’s Maximum Principle to determine the optimal control strategies for an epidemic and the corresponding minimum antiviral stockpiles. Antiviral treatment was found to be the most effective measure to control new influenza outbreaks. In the case of inadequate antiviral resources, the preferred approach was the centralized use of antiviral resources in the early stage of the epidemic. Immigration detection was the least cost-effective; however, when used in combination with the other measures, it may play a larger role. The reasonable mix of the three control measures could reduce the number of clinical cases substantially, to achieve the optimal control of new influenza. [ABSTRACT FROM AUTHOR]

Individual behavioral response to the spreading of an epidemic plays a crucial role in the progression of the epidemic itself. The risk perception induces individuals to adopt a protective behavior, as for instance reducing their social contacts, adopting more restrictive hygienic measures or undergoing prophylaxis procedures. In this paper, starting with a previously developed lattice-gas SIR model, we construct a coupled behavior-disease model for influenza spreading with spontaneous behavioral changes. The focus is on self-initiated behavioral changes that alter the susceptibility to the disease, without altering the contact patterns among individuals. Three different mechanisms of awareness spreading are analyzed: the local spreading due to the presence in the neighborhood of infective individuals; the global spreading due to the news published by the mass media and to educational campaigns implemented at institutional level; the local spreading occurring through the “thought contagion” among aware and unaware individuals. The peculiarity of the present approach is that the awareness spreading model is calibrated on available data on awareness and concern of the population about the risk of contagion. In particular, the model is validated against the A(H1N1) epidemic outbreak in Italy during the season, by making use of the awareness data gathered by the behavioral risk factor surveillance system (PASSI). We find that, increasing the accordance between the simulated awareness spreading and the PASSI data on risk perception, the agreement between simulated and experimental epidemiological data improves as well. Furthermore, we show that, within our model, the primary mechanism to reproduce a realistic evolution of the awareness during an epidemic, is the one due to globally available information. This result highlights how crucial is the role of mass media and educational campaigns in influencing the epidemic spreading of infectious diseases. [ABSTRACT FROM AUTHOR]

The clinical serial interval of an infectious disease is the time between date of symptom onset in an index case and the date of symptom onset in one of its secondary cases. It is a quantity which is commonly collected during a pandemic and is of fundamental importance to public health policy and mathematical modelling. In this paper we present a novel method for calculating the serial interval distribution for a Markovian model of household transmission dynamics. This allows the use of Bayesian MCMC methods, with explicit evaluation of the likelihood, to fit to serial interval data and infer parameters of the underlying model. We use simulated and real data to verify the accuracy of our methodology and illustrate the importance of accounting for household size. The output of our approach can be used to produce posterior distributions of population level epidemic characteristics. [ABSTRACT FROM AUTHOR]

Involved in many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, G-protein-coupled receptors (GPCRs) are among the most frequent targets of therapeutic drugs. It is time-consuming and expensive to determine whether a drug and a GPCR are to interact with each other in a cellular network purely by means of experimental techniques. Although some computational methods were developed in this regard based on the knowledge of the 3D (dimensional) structure of protein, unfortunately their usage is quite limited because the 3D structures for most GPCRs are still unknown. To overcome the situation, a sequence-based classifier, called “iGPCR-drug”, was developed to predict the interactions between GPCRs and drugs in cellular networking. In the predictor, the drug compound is formulated by a 2D (dimensional) fingerprint via a 256D vector, GPCR by the PseAAC (pseudo amino acid composition) generated with the grey model theory, and the prediction engine is operated by the fuzzy K-nearest neighbour algorithm. Moreover, a user-friendly web-server for iGPCR-drug was established at http://www.jci-bioinfo.cn/iGPCR-Drug/. For the convenience of most experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated math equations presented in this paper just for its integrity. The overall success rate achieved by iGPCR-drug via the jackknife test was 85.5%, which is remarkably higher than the rate by the existing peer method developed in 2010 although no web server was ever established for it. It is anticipated that iGPCR-Drug may become a useful high throughput tool for both basic research and drug development, and that the approach presented here can also be extended to study other drug – target interaction networks. [ABSTRACT FROM AUTHOR]

The number of travel-acquired dengue infections has seen a consistent global rise over the past decade. An increased volume of international passenger air traffic originating from regions with endemic dengue has contributed to a rise in the number of dengue cases in both areas of endemicity and elsewhere. This paper reports results from a network-based risk assessment model which uses international passenger travel volumes, travel routes, travel distances, regional populations, and predictive species distribution models (for the two vector species, Aedes aegypti and Aedes albopictus) to quantify the relative risk posed by each airport in importing passengers with travel-acquired dengue infections. Two risk attributes are evaluated: (i) the risk posed by through traffic at each stopover airport and (ii) the risk posed by incoming travelers to each destination airport. The model results prioritize optimal locations (i.e., airports) for targeted dengue surveillance. The model is easily extendible to other vector-borne diseases. [ABSTRACT FROM AUTHOR]

This paper explores the effect of social relations and gender-based conflicts on the uptake of HIV testing in the South and Central provinces of Zambia. We conducted a community-based cross-sectional study of 1716 randomly selected individuals. Associations were examined using mixed-effect multivariable logistic regression. A total of 264 men (64%) and 268 women (56%) had never tested for HIV. The strongest determinants for not being tested were disruptive couple relationships (OR = 2.48 95% CI = 1.00–6.19); tolerance to gender-based violence (OR = 2.10 95% CI = 1.05–4.32) and fear of social rejection (OR = 1.48 95% CI = 1.23–1.80). In the Zambian context, unequal power relationships within the couple and the community seem to play a pivotal role in the decision to test which until now have been largely underestimated. Policies, programs and interventions to rapidly increase HIV testing need to urgently address gender-power inequity in relationships and prevent gender-based violence to reduce the negative impact on the lives of couples and families. [ABSTRACT FROM AUTHOR]

Developing appropriate risk messages during challenging situations like public health outbreaks is complicated. The focus of this paper is on how First Nations and Metis people in Manitoba, Canada, responded to the public health management of pandemic H1N1, using a focus group methodology (n = 23 focus groups). Focus group conversations explored participant reactions to messaging regarding the identification of H1N1 virus risk groups, the H1N1 vaccine and how priority groups to receive the vaccine were established. To better contextualize the intentions of public health professionals, key informant interviews (n = 20) were conducted with different health decision makers (e.g., public health officials, people responsible for communications, representatives from some First Nations and Metis self-governing organizations). While risk communication practice has improved, ‘one size’ messaging campaigns do not work effectively, particularly when communicating about who is most ‘at-risk’. Public health agencies need to pay more attention to the specific socio-economic, historical and cultural contexts of First Nations and Metis citizens when planning for, communicating and managing responses associated with pandemic outbreaks to better tailor both the messages and delivery. More attention is needed to directly engage First Nations and Metis communities in the development and dissemination of risk messaging. [ABSTRACT FROM AUTHOR]