Mystery of the Ravenspurs, The by WHITE, Fred M.

The Ravenspurs have for generations resided quietly in prosperity and comfort at their seaside castle. But the clan is suddenly besieged with strange happenings which are dwindling the population of the family to only a few which remain, and those few find themselves in fear of becoming the very last of the powerful family if the cause of their untimely deaths and disappearances is not uncovered soon. It will take a great deal of detective work and a touch of travel to help unravel the mystery of the Ravenspurs. (Roger Melin)
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Vector competence of populations of <i>Aedes aegypti</i> from three distinct cities in Kenya for chikungunya virus

by Sheila B. Agha, Edith Chepkorir, Francis Mulwa, Caroline Tigoi, Samwel Arum, Milehna M. Guarido, Peris Ambala, Betty Chelangat, Joel Lutomiah, David P. Tchouassi, Michael J. Turell, Rosemary Sang

Background

In April, 2004, chikungunya virus (CHIKV) re-emerged in Kenya and eventually spread to the islands in the Indian Ocean basin, South-East Asia, and the Americas. The virus, which is often associated with high levels of viremia in humans, is mostly transmitted by the urban vector, Aedes aegypti. The expansion of CHIKV presents a public health challenge both locally and internationally. In this study, we investigated the ability of Ae. aegypti mosquitoes from three distinct cities in Kenya; Mombasa (outbreak prone), Kisumu, and Nairobi (no documented outbreak) to transmit CHIKV.

Methodology/Principal findings

Aedes aegypti mosquito populations were exposed to different doses of CHIKV (105.6–7.5 plaque-forming units[PFU]/ml) in an infectious blood meal. Transmission was ascertained by collecting and testing saliva samples from individual mosquitoes at 5, 7, 9, and 14 days post exposure. Infection and dissemination were estimated by testing body and legs, respectively, for individual mosquitoes at selected days post exposure. Tissue culture assays were used to determine the presence of infectious viral particles in the body, leg, and saliva samples. The number of days post exposure had no effect on infection, dissemination, or transmission rates, but these rates increased with an increase in exposure dose in all three populations. Although the rates were highest in Ae. aegypti from Mombasa at titers ≥106.9 PFU/ml, the differences observed were not statistically significant (χ2 ≤ 1.04, DF = 1, P ≥ 0.31). Overall, about 71% of the infected mosquitoes developed a disseminated infection, of which 21% successfully transmitted the virus into a capillary tube, giving an estimated transmission rate of about 10% for mosquitoes that ingested ≥106.9 PFU/ml of CHIKV. All three populations of Ae. aegypti were infectious as early as 5–7 days post exposure. On average, viral dissemination only occurred when body titers were ≥104 PFU/ml in all populations.

Conclusions/Significance

Populations of Ae. aegypti from Mombasa, Nairobi, and Kisumu were all competent laboratory vectors of CHIKV. Viremia of the infectious blood meal was an important factor in Ae. aegypti susceptibility and transmission of CHIKV. In addition to viremia levels, temperature and feeding behavior of Ae. aegypti may also contribute to the observed disease patterns.

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Expression of interferon-inducible chemokines and sleep/wake changes during early encephalitis in experimental African trypanosomiasis

by Claudia Laperchia, Chiara Tesoriero, Paul F. Seke-Etet, Valentina La Verde, Valeria Colavito, Gigliola Grassi-Zucconi, Jean Rodgers, Paul Montague, Peter G. E. Kennedy, Marina Bentivoglio

Background

Human African trypanosomiasis or sleeping sickness, caused by the parasite Trypanosoma brucei, leads to neuroinflammation and characteristic sleep/wake alterations. The relationship between the onset of these alterations and the development of neuroinflammation is of high translational relevance, but remains unclear. This study investigates the expression of interferon (IFN)-γ and IFN-inducible chemokine genes in the brain, and the levels of CXCL10 in the serum and cerebrospinal fluid prior to and during the encephalitic stage of trypanosome infection, and correlates these with sleep/wake changes in a rat model of the disease.

Methodology/Principal findings

The expression of genes encoding IFN-γ, CXCL9, CXCL10, and CXCL11 was assessed in the brain of rats infected with Trypanosoma brucei brucei and matched controls using semi-quantitative end-point RT-PCR. Levels of CXCL10 in the serum and cerebrospinal fluid were determined using ELISA. Sleep/wake states were monitored by telemetric recording. Using immunohistochemistry, parasites were found in the brain parenchyma at 14 days post-infection (dpi), but not at 6 dpi. Ifn-γ, Cxcl9, Cxcl10 and Cxcl11 mRNA levels showed moderate upregulation by 14 dpi followed by further increase between 14 and 21 dpi. CXCL10 concentration in the cerebrospinal fluid increased between 14 and 21 dpi, preceded by a rise in the serum CXCL10 level between 6 and 14 dpi. Sleep/wake pattern fragmentation was evident at 14 dpi, especially in the phase of wake predominance, with intrusion of sleep episodes into wakefulness.

Conclusions/Significance

The results show a modest increase in Cxcl9 and Cxcl11 transcripts in the brain and the emergence of sleep/wake cycle fragmentation in the initial encephalitic stage, followed by increases in Ifn-γ and IFN-dependent chemokine transcripts in the brain and of CXCL10 in the cerebrospinal fluid. The latter parameter and sleep/wake alterations could provide combined humoral and functional biomarkers of the early encephalitic stage in African trypanosomiasis.

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Correlation between mosquito larval density and their habitat physicochemical characteristics in Mazandaran Province, northern Iran

by Seyed Hassan Nikookar, Mahmoud Fazeli-Dinan, Shahyad Azari-Hamidian, Seyed Nouraddin Mousavinasab, Mohsen Aarabi, Seyyed Payman Ziapour, Yahya Esfandyari, Ahmadali Enayati

Characteristics of mosquito larval habitats are important in determining whether they can survive and successfully complete their developmental stages. Therefore, data on the ecological factors affecting mosquito density and abundance especially the physicochemical properties of water of their breeding sites, can possibly be helpful in implementing larval management programs. Mosquito larvae were collected using a standard 350 ml dipper from fixed habitats including: artificial pool, river edge, creek and etc, in 30 villages of 16 counties from May-December 2014. Water samples were collected during larval collection and temperature (°C), acidity (pH), turbidity (NTU), electrical conductivity (μS/cm), alkalinity (mg/l CaCO3), total hardness (mg/l), nitrate (mg/l), chloride (mg/l), phosphate (mg/l) and sulphate (mg/l) were measured using standard methods. Spearman correlation coefficient, Kruskal-Wallis test of nonparametric analysis, Chi-square (χ2) analysis, regression analysis and C8 interspecific correlation coefficient were used for data analysis. A total of 7,566 mosquito larvae belonging to 15 species representing three genera were collected from fixed larval breeding places. Culex pipiens was the dominant species except in four villages where An. maculipennis s.l. and Cx. torrentium were predominant. There was a significant positive correlation between the density of Cx. pipiens and electrical conductivity, alkalinity, total hardness and chloride, whereas no significant negative correlation was observed between physicochemical factors and larval density. The highest interspecific association of up to 0.596 was observed between An. maculipennis s.l/An. pseudopictus followed by up to 0.435 between An. maculipennis s.l/An. hyrcanus and An. hyrcanus/An. pseudopictus. The correlations observed between physicochemical factors and larval density, can possibly confirm the effect of these parameters on the breeding activities of mosquitoes, and may be indicative of the presence of certain mosquito fauna in a given region.

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The location of Australian Buruli ulcer lesions—Implications for unravelling disease transmission

by Arvind Yerramilli, Ee Laine Tay, Andrew J. Stewardson, Peter G. Kelley, Emma Bishop, Grant A. Jenkin, Mike Starr, Janine Trevillyan, Andrew Hughes, N Deborah Friedman, Daniel P. O’Brien, Paul D. R. Johnson

Background

Buruli ulcer (BU), caused by Mycobacterium ulcerans, is increasing in incidence in Victoria, Australia. To improve understanding of disease transmission, we aimed to map the location of BU lesions on the human body.

Methods

Using notification data and clinical records review, we conducted a retrospective observational study of patients diagnosed with BU in Victoria from 1998–2015. We created electronic density maps of lesion locations using spatial analysis software and compared lesion distribution by age, gender, presence of multiple lesions and month of infection.

Findings

We examined 579 patients with 649 lesions; 32 (5.5%) patients had multiple lesions. Lesions were predominantly located on lower (70.0%) and upper (27.1%) limbs, and showed a non-random distribution with strong predilection for the ankles, elbows and calves. When stratified by gender, upper limb lesions were more common (OR 1·97, 95% CI 1·38–2·82, p<0·001) while lower limb lesions were less common in men than in women (OR 0·48, 95% CI 0·34–0·68, p<0·001). Patients aged ≥ 65 years (OR 3·13, 95% CI 1·52–6·43, p = 0·001) and those with a lesion on the ankle (OR 2·49, 95% CI 1·14–5·43, p = 0·02) were more likely to have multiple lesions. Most infections (71.3%) were likely acquired in the warmer 6 months of the year.

Interpretation

Comparison with published work in Cameroon, Africa, showed similar lesion distribution and suggests the mode of M. ulcerans transmission may be the same across the globe. Our findings also aid clinical diagnosis and provide quantitative background information for further research investigating disease transmission.

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A strategy for scaling up access to comprehensive care in adults with Chagas disease in endemic countries: The Bolivian Chagas Platform

by Maria-Jesus Pinazo, Jimy Pinto, Lourdes Ortiz, Jareth Sánchez, Wilson García, Ruth Saravia, Mirko-R Cortez, Silvia Moriana, Enric Grau, Daniel Lozano, Joaquim Gascon, Faustino Torrico

Background

Bolivia has the highest prevalence of Chagas disease (CD) in the world (6.1%), with more than 607,186 people with Trypanosoma cruzi infection, most of them adults. In Bolivia CD has been declared a national priority. In 2009, the Chagas National Program (ChNP) had neither a protocol nor a clear directive for diagnosis and treatment of adults. Although programs had been implemented for congenital transmission and for acute cases, adults remained uncovered. Moreover, health professionals were not aware of treatment recommendations aimed at this population, and research on CD was limited; it was difficult to increase awareness of the disease, understand the challenges it presented, and adapt strategies to cope with it. Simultaneously, migratory flows that led Bolivian patients with CD to Spain and other European countries forced medical staff to look for solutions to an emerging problem.

Intervention

In this context, thanks to a Spanish international cooperation collaboration, the Bolivian platform for the comprehensive care of adults with CD was created in 2009. Based on the establishment of a vertical care system under the umbrella of ChNP general guidelines, six centres specialized in CD management were established in different epidemiological contexts. A common database, standardized clinical forms, a and a protocolized attention to adults patients, together with training activities for health professionals were essential for the model success. With the collaboration and knowledge transfer activities between endemic and non-endemic countries, the platform aims to provide care, train health professionals, and create the basis for a future expansion to the National Health System of a proven model of care for adults with CD.

Results

From 2010 to 2015, a total of 26,227 patients were attended by the Platform, 69% (18,316) were diagnosed with T. cruzi, 8,567 initiated anti-parasitic treatment, more than 1,616 health professionals were trained, and more than ten research projects developed. The project helped to increase the number of adults with CD diagnosed and treated, produce evidence-based clinical practice guidelines, and bring about changes in policy that will increase access to comprehensive care among adults with CD. The ChNP is now studying the Platform’s health care model to adapt and implement it nationwide.

Conclusions

This strategy provides a solution to unmet demands in the care of patients with CD, improving access to diagnosis and treatment. Further scaling up of diagnosis and treatment will be based on the expansion of the model of care to the NHS structures. Its sustainability will be ensured as it will build on existing local resources in Bolivia. Still human trained resources are scarce and the high staff turnover in Bolivia is a limitation of the model. Nevertheless, in a preliminary two-years-experience of scaling up this model, this limitations have been locally solved together with the health local authorities.

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Persistent infection due to a small-colony variant of <i>Burkholderia pseudomallei</i> leads to PD-1 upregulation on circulating immune cells and mononuclear infiltration in viscera of experimental BALB/c mice

by Jia-Xiang See, Samudi Chandramathi, Mahmood Ameen Abdulla, Jamuna Vadivelu, Esaki M. Shankar

Background

Melioidosis is a neglected tropical disease endemic across South East Asia and Northern Australia. The etiological agent, Burkholderia pseudomallei (B.pseudomallei), is a Gram-negative, rod-shaped, motile bacterium residing in the soil and muddy water across endemic regions of the tropical world. The bacterium is known to cause persistent infections by remaining latent within host cells for prolonged duration. Reactivation of the recrudescent disease often occurs in elders whose immunity wanes. Moreover, recurrence rates in melioidosis patients can be up to ~13% despite appropriate antibiotic therapy, suggestive of bacterial persistence and inefficacy of antibiotic regimens. The mechanisms behind bacterial persistence in the host remain unclear, and hence understanding host immunity during persistent B. pseudomallei infections may help designing potential immunotherapy.

Methodology/Principal findings

A persistent infection was generated using a small-colony variant (SCV) and a wild-type (WT) B. pseudomallei in BALB/c mice via intranasal administration. Infected mice that survived for >60 days were sacrificed. Lungs, livers, spleens, and peripheral blood mononuclear cells were harvested for experimental investigations. Histopathological changes of organs were observed in the infected mice, suggestive of successful establishment of persistent infections. Moreover, natural killer (NK) cell frequency was increased in SCV- and WT-infected mice. We observed programmed death-1 (PD-1) upregulation on B cells of SCV- and WT-infected mice. Interestingly, PD-1 upregulation was only observed on NK cells and monocytes of SCV-infected mice. In contrast, cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) downregulation was seen on NK cells of WT-infected mice, and on monocytes of SCV- and WT-infected mice.

Conclusions/Significance

The SCV and the WT of B. pseudomallei distinctly upregulated PD-1 expression on B cells, NK cells, and monocytes to dampen host immunity, which likely facilitates bacterial persistence. PD-1/PD-L1 pathway appears to play an important role in the persistence of B. pseudomallei in the host.

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We are not Charlie and we will never be.