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Preheating of urine improves the specificity of urinary cryptococcal antigen testing using the lateral flow assay

PLoS Neglected Tropical Diseases News - 11 May 2017 - 9:00pm

by Fábio Brito-Santos, Marcela de Faria Ferreira, Luciana Trilles, Mauro de Medeiros Muniz, Valdiléa Gonçalves Veloso dos Santos, Filipe Anibal Carvalho-Costa, Wieland Meyer, Bodo Wanke, Márcia dos Santos Lazéra

Melioidosis: Clinical impact and public health threat in the tropics

PLoS Neglected Tropical Diseases News - 11 May 2017 - 9:00pm

by Ramar Perumal Samy, Bradley G. Stiles, Gautam Sethi, Lina H. K. Lim

This review briefly summarizes the geographical distribution and clinical impact of melioidosis, especially in the tropics. Burkholderia pseudomallei (a gram-negative bacterium) is the major causative agent for melioidosis, which is prevalent in Singapore, Malaysia, Thailand, Vietnam, and Northern Australia. Melioidosis patients are increasingly being recognized in other parts of the world. The bacteria are intrinsically resistant to many antimicrobial agents, but prolonged treatment, especially with combinations of antibiotics, may be effective. Despite therapy, the overall case fatality rate of septicemia in melioidosis remains significantly high. Intracellular survival of the bacteria within macrophages may progress to chronic infections, and about 10% of patients suffer relapses. In the coming decades, melioidosis will increasingly afflict travelers throughout many global regions. Clinicians managing travelers returning from the subtropics or tropics with severe pneumonia or septicemia should consider acute melioidosis as a differential diagnosis. Patients with open skin wounds, diabetes, or chronic renal disease are at higher risk for melioidosis and should avoid direct contact with soil and standing water in endemic regions. Furthermore, there are fears that B. pseudomallei may be used as a biological weapon. Technological advancements in molecular diagnostics and antibiotic therapy are improving the disease outcomes in endemic areas throughout Asia. Research and development efforts on vaccine candidates against melioidosis are ongoing.

Time trend of neurocysticercosis in children with seizures in a tertiary hospital of western Nepal

PLoS Neglected Tropical Diseases News - 10 May 2017 - 9:00pm

by Kalipatnam Seshagiri Rao, Sudhir Adhikari, Eva Gauchan, Brijesh Sathian, Ganesh B. K., Sahisnuta Basnet, Prabhat Kumar Tiwari, Namraj Bahadur, Rajnish Mishra

Introduction

Neurocysticercosis is a common cause of seizure disorders in children of Western Nepal. The clinical presentation is variable. The incidence varies depending on the food habits and ethnicity of the population. The present study was undertaken with the objective of studying the mode of presentation, radiological findings and to determine the recent trend of the disease in children of Western Nepal.

Methods

Records from the Department of Pediatrics, Manipal Teaching Hospital, Pokhara, Nepal of children aged 0–17 years admitted from 2003 to 2015 and with the discharge diagnosis of seizure and neurocysticercosis (NCC) were reviewed. The diagnosis was primarily based on clinical features, neurological involvement and CT and MRI studies. Seizures due to other CNS pathologies were excluded. Patients with NCC were treated with Albendazole15mg/kg/day for 28 days with supportive treatments for seizures and raised intracranial pressure. Patients were followed up for one year after the completion of the treatment.

Results

There were 1355 cases of seizure disorders, out of which 229 (16.90%) were NCC. There were 99 (43.23%) in the age group 6–10 years followed by 91 (41.09%) in the age group of 11–15 years. Seizures were the most common presenting symptom in 88.65%, followed by raised ICP in 9.61%. Neuropsychiatric changes were noted in 38 cases (16.59%). CT scan findings revealed single lesion in 78.16% and multiple lesions in 21.83%. Poisson regression analysis showed statistically significant decline of year-wise incidence of NCC cases (p<0.05) from 2003 to 2015.

Conclusion

The decline in the incidence of NCC in recent years is most probably attributed to improved hygiene with the construction of household toilets to avoid open free defecation and biannual deworming with Albendazole as a part of School Health and Nutrition Project.

Functional and phenotypic evaluation of eosinophils from patients with the acute form of paracoccidioidomycosis

PLoS Neglected Tropical Diseases News - 10 May 2017 - 9:00pm

by Fernanda Gambogi Braga, Luciana Pereira Ruas, Ricardo Mendes Pereira, Xinaida Taligare Lima, Edson Antunes, Ronei Luciano Mamoni, Maria Heloisa Souza Lima Blotta

Background

Eosinophilia is a typical finding of the acute/juvenile form of paracoccidioidomycosis (PCM), a systemic mycosis endemic in Latin America. This clinical form is characterized by depressed cellular immune response and production of Th2 cytokines. Moreover, it has been shown that the increased number of eosinophils in peripheral blood of patients returns to normal values after antifungal treatment. However, the role of eosinophils in PCM has never been evaluated. This study aimed to assess the phenotypic and functional characteristics of eosinophils in PCM.

Methods/Principal findings

In 15 patients with the acute form of the disease, we detected expression of MBP, CCL5 (RANTES) and CCL11 (eotaxin) in biopsies of lymph nodes and liver. In addition, there were higher levels of chemokines and granule proteins in the peripheral blood of patients compared to controls. Isolation of eosinophils from blood revealed a higher frequency of CD69+ and TLR2+ eosinophils in patients compared to controls, and a lower population of CD80+ cells. We also evaluated the fungicidal capacity of eosinophils in vitro. Our results revealed that eosinophils from PCM patients and controls exhibit similar ability to kill P. brasiliensis yeast cells, although eosinophils of patients were less responsive to IL-5 stimulation than controls.

Conclusion/Principal findings

In conclusion, we suggest that eosinophils might play a role in the host response to fungi and in the pathophysiology of PCM by inducing an intense and systemic inflammatory response in the initial phase of the infection.

An environmental assessment and risk map of <i>Ascaris lumbricoides</i> and <i>Necator americanus</i> distributions in Manufahi District, Timor-Leste

PLoS Neglected Tropical Diseases News - 10 May 2017 - 9:00pm

by Rebecca Wardell, Archie C. A. Clements, Aparna Lal, David Summers, Stacey Llewellyn, Suzy J. Campbell, James McCarthy, Darren J. Gray, Susana V. Nery

Background

In Timor-Leste there have been intermittent and ineffective soil-transmitted helminth (STH) deworming programs since 2004. In a resource-constrained setting, having information on the geographic distribution of STH can aid in prioritising high risk communities for intervention. This study aimed to quantify the environmental risk factors for STH infection and to produce a risk map of STH in Manufahi district, Timor-Leste.

Methodology/Principal findings

Georeferenced cross-sectional data and stool samples were obtained from 2,194 participants in 606 households in 24 villages in the Manufahi District as part of cross sectional surveys done in the context of the “WASH for Worms” randomised controlled trial. Infection status was determined for Ascaris lumbricoides and Necator americanus using real-time quantitative polymerase chain reaction. Baseline infection data were linked to environmental data obtained for each household. Univariable and multivariable multilevel mixed-effects logistic regression analysis with random effects at the village and household level were conducted, with all models adjusted for age and sex. For A. lumbricoides, being a school-aged child increased the odds of infection, whilst higher temperatures in the coolest quarter of the year, alkaline soils, clay loam/loam soils and woody savannas around households were associated with decreased infection odds. For N. americanus, greater precipitation in the driest month, higher average enhanced vegetation index, age and sandy loam soils increased infection odds, whereas being female and living at higher elevations decreased the odds of infection. Predictive risk maps generated for Manufahi based upon these final models highlight the high predicted risk of N. americanus infection across the district and the more focal nature of A. lumbricoides infection. The predicted risk of any STH infection is high across the entire district.

Conclusions/Significance

The widespread predicted risk of any STH infection in 6 to 18 year olds provides strong evidence to support strategies for control across the entire geographical area. As few studies include soil texture and pH in their analysis, this study adds to a growing body of evidence suggesting these factors influence STH infection distribution. This study also further supports that A. lumbricoides prefers acidic soils, highlighting a potential relatively unexplored avenue for control.

Trial registration

ClinicalTrials.gov ACTRN12614000680662.

<i>Haemophilus ducreyi</i> DNA is detectable on the skin of asymptomatic children, flies and fomites in villages of Papua New Guinea

PLoS Neglected Tropical Diseases News - 10 May 2017 - 9:00pm

by Wendy Houinei, Charmie Godornes, August Kapa, Sascha Knauf, Eric Q. Mooring, Camila González-Beiras, Ronald Watup, Raymond Paru, Paul Advent, Sivauk Bieb, Sergi Sanz, Quique Bassat, Stanley M. Spinola, Sheila A. Lukehart, Oriol Mitjà

Background

Haemophilus ducreyi and Treponema pallidum subsp. pertenue are major causes of leg ulcers in children in Africa and the Pacific Region. We investigated the presence of DNA (PCR positivity) from these bacteria on asymptomatic people, flies, and household linens in an endemic setting.

Methodology/Principal findings

We performed a cross-sectional study in rural villages of Lihir Island, Papua New Guinea during a yaws elimination campaign. Participants were asymptomatic subjects recruited from households with cases of leg ulcers, and from households without cases of leg ulcers. We rubbed swabs on the intact skin of the leg of asymptomatic individuals, and collected flies and swabs of environmental surfaces. All specimens were tested by PCR for H. ducreyi and T. p. pertenue DNA. Of 78 asymptomatic participants that had an adequate specimen for DNA detection, H. ducreyi-PCR positivity was identified in 16 (21%) and T. p. pertenue-PCR positivity in 1 (1%). In subgroup analyses, H. ducreyi-PCR positivity did not differ in participants exposed or not exposed to a case of H. ducreyi ulcer in the household (24% vs 18%; p = 0.76). Of 17 cultures obtained from asymptomatic participants, 2 (12%) yielded a definitive diagnosis of H. ducreyi, proving skin colonization. Of 10 flies tested, 9 (90%) had H. ducreyi DNA and 5 (50%) had T. p. pertenue DNA. Of 6 bed sheets sampled, 2 (33%) had H. ducreyi DNA and 1 (17%) had T. p. pertenue DNA.

Conclusions/Significance

This is the first time that H. ducreyi DNA and colonization has been demonstrated on the skin of asymptomatic children and that H. ducreyi DNA and T. p. pertenue DNA has been identified in flies and on fomites. The ubiquity of H. ducreyi in the environment is a contributing factor to the spread of the organism.

Migratory phase of <i>Litomosoides sigmodontis</i> filarial infective larvae is associated with pathology and transient increase of S100A9 expressing neutrophils in the lung

by Gregory Karadjian, Frédéric Fercoq, Nicolas Pionnier, Nathaly Vallarino-Lhermitte, Emilie Lefoulon, Adélaïde Nieguitsila, Sabine Specht, Leo M. Carlin, Coralie Martin

Filarial infections are tropical diseases caused by nematodes of the Onchocercidae family such as Mansonella perstans. The infective larvae (L3) are transmitted into the skin of vertebrate hosts by blood-feeding vectors. Many filarial species settle in the serous cavities including M. perstans in humans and L. sigmodontis, a well-established model of filariasis in mice. L. sigmodontis L3 migrate to the pleural cavity where they moult into L4 around day 9 and into male and female adult worms around day 30. Little is known of the early phase of the parasite life cycle, after the L3 is inoculated in the dermis by the vector and enters the afferent lymphatic vessels and before the moulting processes in the pleural cavity. Here we reveal a pulmonary phase associated with lung damage characterized by haemorrhages and granulomas suggesting L3 reach the lung via pulmonary capillaries and damage the endothelium and parenchyma by crossing them to enter the pleural cavity. This study also provides evidence for a transient inflammation in the lung characterized by a very early recruitment of neutrophils associated with high expression levels of S100A8 and S100A9 proteins.

Zika virus-like particle (VLP) based vaccine

by Hélène Boigard, Alexandra Alimova, George R. Martin, Al Katz, Paul Gottlieb, Jose M. Galarza

The newly emerged mosquito-borne Zika virus poses a major public challenge due to its ability to cause significant birth defects and neurological disorders. The impact of sexual transmission is unclear but raises further concerns about virus dissemination. No specific treatment or vaccine is currently available, thus the development of a safe and effective vaccine is paramount. Here we describe a novel strategy to assemble Zika virus-like particles (VLPs) by co-expressing the structural (CprME) and non-structural (NS2B/NS3) proteins, and demonstrate their effectiveness as vaccines. VLPs are produced in a suspension culture of mammalian cells and self-assembled into particles closely resembling Zika viruses as shown by electron microscopy studies. We tested various VLP vaccines and compared them to analogous compositions of an inactivated Zika virus (In-ZIKV) used as a reference. VLP immunizations elicited high titers of antibodies, as did the In-ZIKV controls. However, in mice the VLP vaccine stimulated significantly higher virus neutralizing antibody titers than comparable formulations of the In-ZIKV vaccine. The serum neutralizing activity elicited by the VLP vaccine was enhanced using a higher VLP dose and with the addition of an adjuvant, reaching neutralizing titers greater than those detected in the serum of a patient who recovered from a Zika infection in Brazil in 2015. Discrepancies in neutralization levels between the VLP vaccine and the In-ZIKV suggest that chemical inactivation has deleterious effects on neutralizing epitopes within the E protein. This along with the inability of a VLP vaccine to cause infection makes it a preferable candidate for vaccine development.

Abnormal neurobehaviour and impaired memory function as a consequence of <i>Toxocara canis</i>- as well as <i>Toxocara cati</i>-induced neurotoxocarosis

by Elisabeth Janecek, Patrick Waindok, Marion Bankstahl, Christina Strube

Background

Neuroinvasive larvae of the worldwide occurring zoonotic roundworms Toxocara canis and T. cati may induce neurotoxocarosis (NT) in humans, provoking a variety of symptoms including cognitive deficits as well as neurological dysfunctions. An association with neuropsychological disorders has been discussed. Similar symptoms have been described in T. canis-infected mice, whereas data on T. cati-induced NT are rare. Therefore, it was aimed to obtain insights into the impact on neurobehaviour as well as progression of neurological symptoms and behavioural alterations during the course of NT directly comparing T. canis- and T. cati-infected mice as models for human NT.

Methodology/Principal findings

C57BL/6 mice were orally infected with 2000 embryonated T. canis or T. cati eggs, respectively, the control group received tap water. Mice were screened weekly for neurobehavioural alterations and memory function starting one day prior infection until 97 days post infection (pi; T. canis-infection) and day 118 pi (T. cati-infection, uninfected control). Mostly motoric and neurological parameters were affected in T. canis-infected mice starting day 20 pi with severe progression accompanied by stereotypical circling. In contrast, T. cati-infected mice mostly showed reduced response to sudden sound stimulus (indicator for excitability) and flight behaviour starting day 6 pi. Interestingly, enhanced grooming behaviour was observed exclusively in T. cati-infected mice, indicating a possible role of neurotransmitter dysregulation. Reduced exploratory behaviour and memory impairment was observed in both infection groups with delayed onset and less severe progression in T. cati- compared to T. canis-infected mice.

Conclusions/Significance

Results highlight the need to consider T. cati beside T. canis as causative agent of human NT. Findings provide valuable hints towards differences in key regulatory mechanisms during T. canis- and T. cati-induced NT, contributing to a comprehensive picture and consequently a broader understanding of NT, which will aid in developing strategies towards prevention in addition to novel diagnostic and therapeutic approaches.

<i>Brugia malayi</i> microfilariae adhere to human vascular endothelial cells in a C3-dependent manner

by Jan-Hendrik Schroeder, David McCarthy, Tadge Szestak, Darren A. Cook, Mark J. Taylor, Alister G. Craig, Charlotte Lawson, Rachel A. Lawrence

Brugia malayi causes the human tropical disease, lymphatic filariasis. Microfilariae (Mf) of this nematode live in the bloodstream and are ingested by a feeding mosquito vector. Interestingly, in a remarkable co-evolutionary adaptation, Mf appearance in the peripheral blood follows a circadian periodicity and reaches a peak when the mosquito is most likely to feed. For the remaining hours, the majority of Mf sequester in the lung capillaries. This circadian phenomenon has been widely reported and is likely to maximise parasite fitness and optimise transmission potential. However, the mechanism of Mf sequestration in the lungs remains largely unresolved. In this study, we demonstrate that B. malayi Mf can, directly adhere to vascular endothelial cells under static conditions and under flow conditions, they can bind at high (but not low) flow rates. High flow rates are more likely to be experienced diurnally. Furthermore, a non-periodic nematode adheres less efficiently to endothelial cells. Strikingly C3, the central component of complement, plays a crucial role in the adherence interaction. These novel results show that microfilariae have the ability to bind to endothelial cells, which may explain their sequestration in the lungs, and this binding is increased in the presence of inflammatory mediators.

In a randomized trial, the live attenuated tetravalent dengue vaccine TV003 is well-tolerated and highly immunogenic in subjects with flavivirus exposure prior to vaccination

by Stephen S. Whitehead, Anna P. Durbin, Kristen K. Pierce, Dan Elwood, Benjamin D. McElvany, Ellen A. Fraser, Marya P. Carmolli, Cecilia M. Tibery, Noreen A. Hynes, Matthew Jo, Janece M. Lovchik, Catherine J. Larsson, Elena A. Doty, Dorothy M. Dickson, Catherine J. Luke, Kanta Subbarao, Sean A. Diehl, Beth D. Kirkpatrick

Trial registration

ClinicalTrials.gov TV003

Associations between selective attention and soil-transmitted helminth infections, socioeconomic status, and physical fitness in disadvantaged children in Port Elizabeth, South Africa: An observational study

by Stefanie Gall, Ivan Müller, Cheryl Walter, Harald Seelig, Liana Steenkamp, Uwe Pühse, Rosa du Randt, Danielle Smith, Larissa Adams, Siphesihle Nqweniso, Peiling Yap, Sebastian Ludyga, Peter Steinmann, Jürg Utzinger, Markus Gerber

Background

Socioeconomically deprived children are at increased risk of ill-health associated with sedentary behavior, malnutrition, and helminth infection. The resulting reduced physical fitness, growth retardation, and impaired cognitive abilities may impede children’s capacity to pay attention. The present study examines how socioeconomic status (SES), parasitic worm infections, stunting, food insecurity, and physical fitness are associated with selective attention and academic achievement in school-aged children.

Methodology

The study cohort included 835 children, aged 8–12 years, from eight primary schools in socioeconomically disadvantaged neighborhoods of Port Elizabeth, South Africa. The d2-test was utilized to assess selective attention. This is a paper and pencil letter-cancellation test consisting of randomly mixed letters d and p with one to four single and/or double quotation marks either over and/or under each letter. Children were invited to mark only the letters d that have double quotation marks. Cardiorespiratory fitness was assessed via the 20 m shuttle run test and muscle strength using the grip strength test. The Kato-Katz thick smear technique was employed to detect helminth eggs in stool samples. SES and food insecurity were determined with a pre-tested questionnaire, while end of year school results were used as an indicator of academic achievement.

Principal findings

Children infected with soil-transmitted helminths had lower selective attention, lower school grades (academic achievement scores), and lower grip strength (all p<0.05). In a multiple regression model, low selective attention was associated with soil-transmitted helminth infection (p<0.05) and low shuttle run performance (p<0.001), whereas higher academic achievement was observed in children without soil-transmitted helminth infection (p<0.001) and with higher shuttle run performance (p<0.05).

Conclusions/Significance

Soil-transmitted helminth infections and low physical fitness appear to hamper children’s capacity to pay attention and thereby impede their academic performance. Poor academic achievement will make it difficult for children to realize their full potential, perpetuating a vicious cycle of poverty and poor health.

Trial registration

ClinicalTrials.gov ISRCTN68411960

Yaws resurgence in Bankim, Cameroon: The relative effectiveness of different means of detection in rural communities

by Alphonse Um Boock, Paschal Kum Awah, Ferdinand Mou, Mark Nichter

Background

Yaws is an infectious, debilitating and disfiguring disease of poverty that mainly affects children in rural communities in tropical areas. In Cameroon, mass-treatment campaigns carried out in the 1950s reduced yaws to such low levels that it was presumed the disease was eradicated. In 2010, an epidemiological study in Bankim Health District detected 29 cases of yaws. Five different means of detecting yaws in clinical and community settings were initiated in Bankim over the following five years.

Methodology

This observational study reviews data on the number of cases of yaws identified by each of the five yaws detection approaches: 1) passive yaws detection at local clinics after staff attended Neglected Tropical Disease awareness workshops, 2) community-based case detection carried out in remote communities by hospital staff who relied on community health workers to identify cases, 3) yaws screening following mass Buruli Ulcer outreach programs being piloted in the district, 4) school-based screening programs conducted as stand-alone and follow-up activities to mass outreach events, and 5) house to house active surveillance activities conducted in thirty-eight communities. Implementation of each of the four community-based approaches was observed by a team of health social scientists tasked with assessing the strengths and limitations of each detection method.

Findings

Eight hundred and fifteen cases of yaws were detected between 2012 and 2015. Only 7% were detected at local clinics. Small outreach programs and household surveys detected yaws in a broad spectrum of communities. The most successful means of yaws detection, accounting for over 70% of cases identified, were mass outreach programs and school based screenings in communities where yaws was detected.

Conclusion

The five interventions for detecting yaws had a synergistic effect and proved to be valuable components of a yaws eradication program. Well planned, culturally sensitive mass outreach educational programs accompanied by school-based programs proved to be particularly effective in Bankim. Including yaws detection in a Buruli Ulcer outreach program constituted a win-win situation, as the demonstration effect of yaws treatment (rapid cure) increased confidence in early Buruli ulcer treatment. Mass outreach programs functioned as magnets for both diseases as well as other kinds of chronic wounds that future outreach programs need to address.

A nonsense mutation in <i>TLR5</i> is associated with survival and reduced IL-10 and TNF-α levels in human Melioidosis

by Panjaporn Chaichana, Narisara Chantratita, Florian Brod, Sirikamon Koosakulnirand, Kemajittra Jenjaroen, Suchintana Chumseng, Manutsanun Sumonwiriya, Mary N. Burtnick, Paul J. Brett, Prapit Teparrukkul, Direk Limmathurotsakul, Nicholas P. J. Day, Susanna J. Dunachie, T. Eoin West

Background

Melioidosis, caused by the flagellated bacterium Burkholderia pseudomallei, is a life-threatening and increasingly recognized emerging disease. Toll-like receptor (TLR) 5 is a germline-encoded pattern recognition receptor to bacterial flagellin. We evaluated the association of a nonsense TLR5 genetic variant that truncates the receptor with clinical outcomes and with immune responses in melioidosis.

Methodology/Principle findings

We genotyped TLR5 c.1174C>T in 194 acute melioidosis patients in Thailand. Twenty-six (13%) were genotype CT or TT. In univariable analysis, carriage of the c.1174C>T variant was associated with lower 28-day mortality (odds ratio (OR) 0.21, 95% confidence interval (CI) 0.05–0.94, P = 0.04) and with lower 90-day mortality (OR 0.25, 95% CI 0.07–086, P = 0.03). In multivariable analysis adjusting for age, sex, diabetes and renal disease, the adjusted OR for 28-day mortality in carriers of the variant was 0.24 (95% CI 0.05–1.08, P = 0.06); and the adjusted OR for 90-day mortality was 0.27 (95% CI 0.08–0.97, P = 0.04). c.1174C>T was associated with a lower rate of bacteremia (P = 0.04) and reduced plasma levels of IL-10 (P = 0.049) and TNF-α (P < 0.0001). We did not find an association between c.1174C>T and IFN-γ ELISPOT (T-cell) responses (P = 0.49), indirect haemagglutination titers or IgG antibodies to bacterial flagellin during acute melioidosis (P = 0.30 and 0.1, respectively).

Conclusions/Significance

This study independently confirms the association of TLR5 c.1174C>T with protection against death in melioidosis, identifies lower bacteremia, IL-10 and TNF-α production in carriers of the variant with melioidosis, but does not demonstrate an association of the variant with acute T-cell IFN-γ response, indirect haemagglutination antibody titer, or anti-flagellin IgG antibodies.

First-time detection and identification of the <i>Mycobacterium tuberculosis</i> Complex members in extrapulmonary tuberculosis clinical samples in south Tunisia by a single tube tetraplex real-time PCR assay

by Mariam Siala, Salma Smaoui, Wafa Taktak, Salma Hachicha, Asma Ghorbel, Chema Marouane, Sana Kammoun, Dhikrayet Gamara, Leila Slim, Radhouane Gdoura, Férièle Messadi-Akrout

Introduction

Tunisia has one of the highest burdens of extrapulmonary tuberculosis (EPTB) among tuberculosis (TB) cases but the contribution of MTBC-mediated human EPTB is unknown. EPTB diagnosis is challenging due to the paucibacillary nature of clinical samples. Therefore, a need of a simplified molecular method for sensitive and specific TB detection and differentiation of MTBC members caused EPTB remains a priority to an early diagnosis, optimize successful anti-TB treatment and minimize transmission. We evaluated the performance of a single tube tetraplex Taq Man real time PCR for EPTB detection and differentiation between MTBC members directly on extrapulmonary samples.

Materials and methods

Extrapulmonary samples obtained from clinically suspected EPTB patients from 2013 to April 2015 were tested by Ziehl Neelsen Staining, mycobacterial culture and qPCR assay for RD1, RD9, RD12 and ext-RD9 targets (MTBC-RD qPCR). The performance of qPCR was compared to a reference standard based on MTBC culture and/or at least two criteria of a composite reference standard (CRS) including clinical, radiological, histopathological and therapeutic findings.

Results

EPTB was identified in 157/170 (92.4%) of included patients of whom 99 (63%) were confirmed by culture and 58 (36.9%) by CRS criteria. The sensitivity and specificity of qPCR, in comparison to the reference standard were 100% (157/157) and 92.3% (12/13), respectively. The sensitivity of qPCR was statistically significant as compared to culture and smear microscopy (P< 0.001). QPCR results showed M. bovis identification in 77.1% of extrapulmonary samples in occurrence to lymphadenitis infection. M. tuberculosis and M.bovis BCG were detected in 21.6% and 1.3% of cases, respectively.

Conclusions

MTBC–RD qPCR proved to be a rapid and sensitive assay for simultaneously TB detection and MTBC members identification on extrapulmonary samples within 1.5 days after sample receipt. Its high sensitivity could make this method a useful tool in diagnosing TB in addition to routine conventional methods and TB clinical parameters.

The impact of migration and antimicrobial resistance on the transmission dynamics of typhoid fever in Kathmandu, Nepal: A mathematical modelling study

by Neil J. Saad, Cayley C. Bowles, Bryan T. Grenfell, Buddha Basnyat, Amit Arjyal, Sabina Dongol, Abhilasha Karkey, Stephen Baker, Virginia E. Pitzer

Background

A substantial proportion of the global burden of typhoid fever occurs in South Asia. Kathmandu, Nepal experienced a substantial increase in the number of typhoid fever cases (caused by Salmonella Typhi) between 2000 and 2003, which subsequently declined but to a higher endemic level than in 2000. This epidemic of S. Typhi coincided with an increase in organisms with reduced susceptibility against fluoroquinolones, the emergence of S. Typhi H58, and an increase in the migratory population in Kathmandu.

Methods

We devised a mathematical model to investigate the potential epidemic drivers of typhoid in Kathmandu and fit this model to weekly data of S. Typhi cases between April 1997 and June 2011 and the age distribution of S. Typhi cases. We used this model to determine if the typhoid epidemic in Kathmandu was driven by heightened migration, the emergence of organisms with reduced susceptibility against fluoroquinolones or a combination of these factors.

Results

Models allowing for the migration of susceptible individuals into Kathmandu alone or in combination with the emergence of S. Typhi with reduced susceptibility against fluoroquinolones provided a good fit for the data. The emergence of organisms with reduced susceptibility against fluoroquinolones organisms alone, either through an increase in disease duration or increased transmission, did not fully explain the pattern of S. Typhi infections.

Conclusions

Our analysis is consistent with the hypothesis that the increase in typhoid fever in Kathmandu was associated with the migration of susceptible individuals into the city and aided by the emergence of reduced susceptibility against fluoroquinolones. These data support identifying and targeting migrant populations with typhoid immunization programmes to prevent transmission and disease.

The effect of current <i>Schistosoma mansoni</i> infection on the immunogenicity of a candidate TB vaccine, MVA85A, in BCG-vaccinated adolescents: An open-label trial

by Anne Wajja, Dennison Kizito, Beatrice Nassanga, Angela Nalwoga, Joyce Kabagenyi, Simon Kimuda, Ronald Galiwango, Gertrude Mutonyi, Samantha Vermaak, Iman Satti, Jaco Verweij, Edridah Tukahebwa, Stephen Cose, Jonathan Levin, Pontiano Kaleebu, Alison M. Elliott, Helen McShane

Introduction

Helminth infection may affect vaccine immunogenicity and efficacy. Adolescents, a target population for tuberculosis booster vaccines, often have a high helminth burden. We investigated effects of Schistosoma mansoni (Sm) on the immunogenicity and safety of MVA85A, a model candidate tuberculosis vaccine, in BCG-vaccinated Ugandan adolescents.

Methods

In this phase II open label trial we enrolled 36 healthy, previously BCG-vaccinated adolescents, 18 with no helminth infection detected, 18 with Sm only. The primary outcome was immunogenicity measured by Ag85A-specific interferon gamma ELISpot assay. Tuberculosis and schistosome-specific responses were also assessed by whole-blood stimulation and multiplex cytokine assay, and by antibody ELISAs.

Results

Ag85A-specific cellular responses increased significantly following immunisation but with no differences between the two groups. Sm infection was associated with higher pre-immunisation Ag85A-specific IgG4 but with no change in antibody levels following immunisation. There were no serious adverse events. Most reactogenicity events were of mild or moderate severity and resolved quickly.

Conclusions

The significant Ag85A-specific T cell responses and lack of difference between Sm-infected and uninfected participants is encouraging for tuberculosis vaccine development. The implications of pre-existing Ag85A-specific IgG4 antibodies for protective immunity against tuberculosis among those infected with Sm are not known. MVA85A was safe in this population.

Trial registration

ClinicalTrials.gov NCT02178748

Global practices in regard to implementation of preventive measures for leprosy

by Laura Gillini, Erwin Cooreman, Tanya Wood, Venkata Rao Pemmaraju, Paul Saunderson

Pages