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Vitamin D status contributes to the antimicrobial activity of macrophages against <i>Mycobacterium leprae</i>

2 July 2018 - 9:00pm

by Elliot W. Kim, Rosane M. B. Teles, Salem Haile, Philip T. Liu, Robert L. Modlin

Background

The immune system depends on effector pathways to eliminate invading pathogens from the host in vivo. Macrophages (MΦ) of the innate immune system are armed with vitamin D-dependent antimicrobial responses to kill intracellular microbes. However, how the physiological levels of vitamin D during MΦ differentiation affect phenotype and function is unknown.

Methodology/principal

The human innate immune system consists of divergent MΦ subsets that serve distinct functions in vivo. Both IL-15 and IL-10 induce MΦ differentiation, but IL-15 induces primary human monocytes to differentiate into antimicrobial MΦ (IL-15 MΦ) that robustly express the vitamin D pathway. However, how vitamin D status alters IL-15 MΦ phenotype and function is unknown. In this study, we found that adding 25-hydroxyvitamin D3 (25D3) during the IL-15 induced differentiation of monocytes into MΦ increased the expression of the antimicrobial peptide cathelicidin, including both CAMP mRNA and the encoded protein cathelicidin in a dose-dependent manner. The presence of physiological levels of 25D during differentiation of IL-15 MΦ led to a significant vitamin D-dependent antimicrobial response against intracellular Mycobacterium leprae but did not change the phenotype or phagocytic function of these MΦ. These data suggest that activation of the vitamin D pathway during IL-15 MΦ differentiation augments the antimicrobial response against M. leprae infection.

Conclusions/significance

Our data demonstrates that the presence of vitamin D during MΦ differentiation bestows the capacity to mount an antimicrobial response against M. leprae.

Non-randomized controlled trial of the long-term efficacy of an Ecohealth intervention against Chagas disease in Yucatan, Mexico

2 July 2018 - 9:00pm

by Etienne Waleckx, Silvia Pérez-Carrillo, Samuel Chávez-Lazo, Rafael Pasos-Alquicira, María Cámara-Heredia, Jesús Acuña-Lizama, Fernando Collí-Balám, Javier Cámara-Mejía, Maria Jesús Ramírez-Sierra, Vladimir Cruz-Chan, Miguel Rosado-Vallado, Santos Vázquez-Narvaez, Rosario Najera-Vázquez, Sébastien Gourbière, Eric Dumonteil

Non-domiciliated intrusive triatomine vectors are responsible for a low but significant transmission of Trypanosoma cruzi to humans. Their control is a challenge as insecticide spraying is of limited usefulness, and alternative strategies need to be developed for a sustainable control. We performed a non-randomized controlled trial of an Ecohealth intervention based on window insect screens and community participation to reduce house infestation by Triatoma dimidiata in two rural villages in Yucatan, Mexico. Efficacy of the intervention was measured over a three years follow-up period and entomological indicators showed that the proportion of triatomines found inside houses was significantly reduced in houses with insect screens, which effectively kept more bugs on the outside of houses. Using a previously developed model linking entomological data to the prevalence of infection in human, we predicted that the intervention would lead to a 32% reduction in yearly incidence and in the prevalence of T. cruzi infection. The cost for the coverage of all the windows of a house was of comparable magnitude to what families currently spend on various domestic insecticide, and most screens were still in good conditions after three years. In conclusion, the Ecohealth approach proposed here is effective for the long-term and sustainable control of intrusive T. dimidiata vectors in the Yucatan peninsula, Mexico. This strategy may also be easily adapted to other intrusive triatomine species as well as other regions/countries with comparable eco-epidemiological settings, and would be an excellent component of a larger integrated program for the control of a variety of other vector-borne diseases, bringing additional benefits to the communities. Our results should encourage a further scaling-up of our implementation strategy in additional villages in the region.

Variation in competence for ZIKV transmission by <i>Aedes aegypti</i> and <i>Aedes albopictus</i> in Mexico

2 July 2018 - 9:00pm

by Selene M. Garcia-Luna, James Weger-Lucarelli, Claudia Rückert, Reyes A. Murrieta, Michael C. Young, Alex D. Byas, Joseph R. Fauver, Rushika Perera, Adriana E. Flores-Suarez, Gustavo Ponce-Garcia, Americo D. Rodriguez, Gregory D. Ebel, William C. Black IV

Background

ZIKV is a new addition to the arboviruses circulating in the New World, with more than 1 million cases since its introduction in 2015. A growing number of studies have reported vector competence (VC) of Aedes mosquitoes from several areas of the world for ZIKV transmission. Some studies have used New World mosquitoes from disparate regions and concluded that these have a variable but relatively low competence for the Asian lineage of ZIKV.

Methodology/Principal findings

Ten Aedes aegypti (L) and three Ae. albopictus (Skuse) collections made in 2016 from throughout Mexico were analyzed for ZIKV (PRVABC59—Asian lineage) VC. Mexican Ae. aegypti had high rates of midgut infection (MIR), dissemination (DIR) and salivary gland infection (SGIR) but low to moderate transmission rates (TR). It is unclear whether this low TR was due to heritable salivary gland escape barriers or to underestimating the amount of virus in saliva due to the loss of virus during filtering and random losses on surfaces when working with small volumes. VC varied among collections, geographic regions and whether the collection was made north or south of the Neovolcanic axis (NVA). The four rates were consistently lower in northeastern Mexico, highest in collections along the Pacific coast and intermediate in the Yucatan. All rates were lowest north of the NVA. It was difficult to assess VC in Ae. albopictus because rates varied depending upon the number of generations in the laboratory.

Conclusions/Significance

Mexican Ae. aegypti and Ae. albopictus are competent vectors of ZIKV. There is however large variance in vector competence among geographic sites and regions. At 14 days post infection, TR varied from 8–51% in Ae. aegypti and from 2–26% in Ae. albopictus.

Domestic animals infected with <i>Mycobacterium ulcerans</i>—Implications for transmission to humans

2 July 2018 - 9:00pm

by Rousseau Djouaka, Francis Zeukeng, Jude Daiga Bigoga, Solange E. Kakou-Ngazoa, Romaric Akoton, Genevieve Tchigossou, David N’golo Coulibaly, Sodjinin Jean-Eudes Tchebe, Sylla Aboubacar, Clavella Nantcho Nguepdjo, Eric Tossou, Razack Adeoti, Thèrèse Marie Ngo Nsonga, Yao Akpo, Innocent Djegbe, Manuele Tamo, Wilfred Fon Mbacham, Anthony Ablordey

Background

The environmental pathogen, Mycobacterium ulcerans (MU) can infect both humans and animals and cause Buruli ulcer (BU) disease. However, its mode(s) of transmission from the colonized environment to human/animal hosts remain unclear. In Australia, MU can infect both wildlife and domestic mammals. Till date, BU-like lesions have only been reported in wildlife in Africa. This warrants a thorough assessment of possible MU in domestic animals in Africa. Here, we screened roaming domesticated animals that share the human microhabitat in two different BU endemic sites, Sedje-Denou in Benin and Akonolinga in Cameroon, for MU lesions.

Methodology/Principal findings

We screened roaming mammals and birds across 3 endemic villages of Sedje-Denou in Southern Benin and 6 endemic villages of Akonolinga in Cameroon. After approval from relevant authorities, specimens (wound swabs and tissue fragments) were collected from animals with open or active lesion and systematically screened to detect the presence of MU though the diagnostic DNA targets IS2404, IS2606 and KR-B. Out of 397 animals surveyed in Akonolinga, 44 (11.08%) carried skin lesions and all were negative for MU DNA. For Sedje-Denou, only 25 (6.93%) out of 361 animals surveyed carried external skin lesions of which 2 (8%) were positive for MU DNA targets. These MU infected lesions were found in two different villages on a goat (abdominal part) and on a dog (nape area of the neck). Source-tracking of MU isolates within infected animal lesions was performed using VNTR genotyping and further confirmed with sequencing. One MU VNTR genotype (Z) was successfully typed from the goat lesion. The evolutionary history inferred from sequenced data revealed a clustering of animal MU isolates within isolates from human lesions.

Conclusion/Significance

This study describes the first report of two MU infected lesions in domestic animals in Africa. Their DNA sequence analyses show close relationship to isolates from human cases. It suggests that MU infection should be suspected in domestic hosts and these could play a role in transmission. The findings further support the hypothesis that MU is a ubiquitous environmental pathogen found in endemic areas, and probably involved in a multiple transmission pathway.

Integrated morbidity mapping of lymphatic filariasis and podoconiosis cases in 20 co-endemic districts of Ethiopia

2 July 2018 - 9:00pm

by Biruk Kebede, Sarah Martindale, Belete Mengistu, Biruck Kebede, Asrat Mengiste, Fikre H/Kiros, Abraham Tamiru, Gail Davey, Louise A. Kelly-Hope, Charles D. Mackenzie

Background

Lymphatic filariasis (LF) and podoconiosis are neglected tropical diseases (NTDs) that pose a significant physical, social and economic burden to endemic communities. Patients affected by the clinical conditions of LF (lymphoedema and hydrocoele) and podoconiosis (lymphoedema) need access to morbidity management and disability prevention (MMDP) services. Clear estimates of the number and location of these patients are essential to the efficient and equitable implementation of MMDP services for both diseases.

Methodology/Principle findings

A community-based cross-sectional study was conducted in Ethiopia using the Health Extension Worker (HEW) network to identify all cases of lymphoedema and hydrocoele in 20 woredas (districts) co-endemic for LF and podoconiosis. A total of 612 trained HEWs and 40 supervisors from 20 districts identified 26,123 cases of clinical morbidity. Of these, 24,908 (95.3%) reported cases had leg lymphoedema only, 751 (2.9%) had hydrocoele, 387 (1.5%) had both leg lymphoedema and hydrocoele, and 77 (0.3%) cases had breast lymphoedema. Of those reporting leg lymphoedema, 89.3% reported bilateral lymphoedema. Older age groups were more likely to have a severe stage of disease, have bilateral lymphoedema and to have experienced an acute attack in the last six months.

Conclusions/Significance

This study represents the first community-wide, integrated clinical case mapping of both LF and podoconiosis in Ethiopia. It highlights the high number of cases, particularly of leg lymphoedema that could be attributed to either of these diseases. This key clinical information will assist and guide the allocation of resources to where they are needed most.

<i>Leishmania major</i> and <i>Trypanosoma lewisi</i> infection in invasive and native rodents in Senegal

29 June 2018 - 9:00pm

by Cécile Cassan, Christophe A. Diagne, Caroline Tatard, Philippe Gauthier, Ambroise Dalecky, Khalilou Bâ, Mamadou Kane, Youssoupha Niang, Mamoudou Diallo, Aliou Sow, Carine Brouat, Anne-Laure Bañuls

Bioinvasion is a major public health issue because it can lead to the introduction of pathogens in new areas and favours the emergence of zoonotic diseases. Rodents are prominent invasive species, and act as reservoirs in many zoonotic infectious diseases. The aim of this study was to determine the link between the distribution and spread of two parasite taxa (Leishmania spp. and Trypanosoma lewisi) and the progressive invasion of Senegal by two commensal rodent species (the house mouse Mus musculus domesticus and the black rat Rattus rattus). M. m. domesticus and R. rattus have invaded the northern part and the central/southern part of the country, respectively. Native and invasive rodents were caught in villages and cities along the invasion gradients of both invaders, from coastal localities towards the interior of the land. Molecular diagnosis of the two trypanosomatid infections was performed using spleen specimens. In the north, neither M. m. domesticus nor the native species were carriers of these parasites. Conversely, in the south, 17.5% of R. rattus were infected by L. major and 27.8% by T. lewisi, while very few commensal native rodents were carriers. Prevalence pattern along invasion gradients, together with the knowledge on the geographical distribution of the parasites, suggested that the presence of the two parasites in R. rattus in Senegal is of different origins. Indeed, the invader R. rattus could have been locally infected by the native parasite L. major. Conversely, it could have introduced the exotic parasite T. lewisi in Senegal, the latter appearing to be poorly transmitted to native rodents. Altogether, these data show that R. rattus is a carrier of both parasites and could be responsible for the emergence of new foci of cutaneous leishmaniasis, or for the transmission of atypical human trypanosomiasis in Senegal.

Molecular detection of <i>Leishmania infantum</i> DNA and host blood meal identification in <i>Phlebotomus</i> in a hypoendemic focus of human leishmaniasis in northern Algeria

29 June 2018 - 9:00pm

by Kahina Bennai, Djamel Tahir, Ismail Lafri, Amina Bendjaballah-Laliam, Idir Bitam, Philippe Parola

Background

Leishmania parasites are transmitted by female phlebotomine sand flies that maintain the enzootic cycle by circulating between sylvatic and domestic mammals. Humans are part of this cycle as accidental hosts due to the vector’s search for a source of blood. In Algeria, Human Leishmaniases (HL) are endemic and represent a serious public health problem because of their high annual incidence and their spread across the country. The aim of this study is to identify sand fly species fauna (vectors of Leishmania), determine their infection rate and identify their feeding preferences using molecular tools in a hypoendemic focus of HL located in the province of Tipaza, northern Algeria.

Methodology/Principal findings

An entomological survey using CDC light traps was conducted between July and October of 2015 in four HL affected peri-urban locations in the province of Tipaza, northern Algeria. Sand flies were identified using the morphological criteria of the genitalia for the males and spermathecae for the females. Leishmania DNA was detected in pooled female sand flies (N = 81 pools with 8–10 specimens per pool) using quantitative real-time polymerase chain reaction (qPCR) targeting two different genes: kDNA-PCR and 18S rRNA. To identify their blood meal sources, blood-fed female sand flies were analyzed by PCR-sequencing targeting the vertebrate cytochrome c oxidase I (COI) gene. A total of 4,045 sand flies were caught, of which 3,727 specimens were morphologically identified. Seven species were recorded: P. (L.) perniciosus (50.28%), P. (L.) perfiliewi (26.13%), P. (L.) longicuspis (21.92%), Sergentomyia (S.) minuta (0.85%), P. (P.) papatasi (0.42%), P. (L.) langeroni (0.32%) and P. (L.) ariasi (0.05%). Afterwards, 740 female specimens were randomly selected and divided into 81 pools and were then screened to investigate the presence of Leishmania spp. L. infantum DNA was detected in three pools, corresponding to three sand fly specimens (one each). The infection rate was 0.33% (2/600) for P. (L.) perniciosus and 2.56% (1/39) for P. (L.) perfiliewi. Analysis of the blood feeding sources (N = 88 specimens) revealed that sand flies belonging to Larroussius subgenera, mainly (71.5%) feed on small ruminants. Human blood is the second feeding source (17%), eight specimens (9%) were found to feed on equines and no domestic reservoir (dog) blood was found.

Conclusions/Significance

The presence of human leishmaniasis cases, the high abundance of Phlebotomus (Larroussius) species which are proven or suspected vectors of L. infantum, and the detection of L. infantum DNA from its natural vectors (P. (L.) perniciosus, P. (L.) perfiliewi), in addition to the blood-feeding of positive females for L. infantum on humans blood, prove that the major elements of the epidemiological transmission cycle of L. infantum are present and indicate risk factors for an outbreak of the disease in the province of Tipaza.

Dengue virus serotype distribution based on serological evidence in pediatric urban population in Indonesia

28 June 2018 - 9:00pm

by R. Tedjo Sasmono, Anne-Frieda Taurel, Ari Prayitno, Hermin Sitompul, Benediktus Yohan, Rahma F. Hayati, Alain Bouckenooghe, Sri Rezeki Hadinegoro, Joshua Nealon

Background

Dengue is a febrile illness transmitted by mosquitoes, causing disease across the tropical and sub-tropical world. Antibody prevalence data and serotype distributions describe population-level risk and inform public health decision-making.

Methodology/Principal findings

In this cross-sectional study we used data from a pediatric dengue seroprevalence study to describe historical dengue serotype circulation, according to age and geographic location. A sub-sample of 780 dengue IgG-positive sera, collected from 30 sites across urban Indonesia in 2014, were tested by the plaque reduction neutralization test (PRNT) to measure the prevalence and concentration of serotype-specific neutralizing antibodies according to subject age and geography. PRNT results were obtained from 776 subjects with mean age of 9.6 years. 765 (98.6%) neutralized one or more dengue serotype at a threshold of >10 (1/dil). Multitypic profiles were observed in 50.9% of the samples; a proportion which increased to 63.1% in subjects aged 15–18 years. Amongst monotypic samples, the highest proportion was reactive against DENV-2, followed by DENV-1, and DENV-3, with some variation across the country. DENV-4 was the least common serotype. The highest anti-dengue antibody titers were recorded against DENV-2, and increased with age to a geometric mean of 516.5 [1/dil] in the oldest age group.

Conclusions/Significance

We found that all four dengue serotypes have been widely circulating in most of urban Indonesia, and more than half of children had already been exposed to >1 dengue serotype, demonstrating intense transmission often associated with more severe clinical episodes. These data will help inform policymakers and highlight the importance of dengue surveillance, prevention and control.

Co-occurrence of opisthorchiasis and diabetes exacerbates morbidity of the hepatobiliary tract disease

28 June 2018 - 9:00pm

by Apisit Chaidee, Sudarat Onsurathum, Kitti Intuyod, Patchareewan Pannangpetch, Chatlert Pongchaiyakul, Porntip Pinlaor, Chawalit Pairojkul, Wannaporn Ittiprasert, Christina J. Cochran, Victoria H. Mann, Paul J. Brindley, Somchai Pinlaor

Complications arising from infection with the carcinogenic liver fluke Opisthorchis viverrini cause substantial morbidity and mortality in Thailand and adjacent lower Mekong countries. In parallel, the incidence rate of diabetes mellitus (DM) is increasing in this same region, and indeed worldwide. Many residents in opisthorchiasis-endemic regions also exhibit DM, but the hepatobiliary disease arising during the co-occurrence of these two conditions remains to be characterized. Here, the histopathological profile during co-occurrence of opisthorchiasis and DM was investigated in a rodent model of human opisthorchiasis in which diabetes was induced with streptozotocin. The effects of excretory/secretory products from the liver fluke, O. viverrini (OVES) on hepatocyte and cholangiocyte responses during hyperglycemic conditions also were monitored. Both the liver fluke-infected hamsters (OV group) and hamsters with DM lost weight compared to control hamsters. Weight loss was even more marked in the hamsters with both opisthorchiasis and DM (OD group). Hypertrophy of hepatocytes, altered biliary canaliculi, and biliary hyperplasia were more prominent in the OD group, compared with OV and DM groups. Profound oxidative DNA damage, evidenced by 8-oxo-2'-deoxyguanosine, proliferating cell nuclear antigen, and periductal fibrosis characterized the OD compared to OV and DM hamsters. Upregulation of expression of cytokines in response to infection and impairment of the pathway for insulin receptor substrate (IRS)/phosphatidylinositol-3-kinases (PI3K)/protein kinase B (AKT) signaling attended these changes. In vitro, OVES and glucose provoked time- and dose-dependent effects on the proliferation of both hepatocytes and cholangiocytes. In overview, the co-occurrence of opisthorchiasis and diabetes exacerbated pathophysiological damage to the hepatobiliary tract. We speculate that opisthorchiasis and diabetes together aggravate hepatobiliary pathogenesis through an IRS/PI3K/AKT-independent pathway.

Evidence of zoonotic leprosy in Pará, Brazilian Amazon, and risks associated with human contact or consumption of armadillos

28 June 2018 - 9:00pm

by Moises B. da Silva, Juliana M. Portela, Wei Li, Mary Jackson, Mercedes Gonzalez-Juarrero, Andrea Sánchez Hidalgo, John T. Belisle, Raquel C. Bouth, Angélica R. Gobbo, Josafá G. Barreto, Antonio H. H. Minervino, Stewart T. Cole, Charlotte Avanzi, Philippe Busso, Marco A. C. Frade, Annemieke Geluk, Claudio G. Salgado, John S. Spencer

Mycobacterium leprae (M. leprae) is a human pathogen and the causative agent for leprosy, a chronic disease characterized by lesions of the skin and peripheral nerve damage. Zoonotic transmission of M. leprae to humans by nine-banded armadillos (Dasypus novemcinctus) has been shown to occur in the southern United States, mainly in Texas, Louisiana, and Florida. Nine-banded armadillos are also common in South America, and residents living in some areas in Brazil hunt and kill armadillos as a dietary source of protein. This study examines the extent of M. leprae infection in wild armadillos and whether these New World mammals may be a natural reservoir for leprosy transmission in Brazil, similar to the situation in the southern states of the U.S. The presence of the M. leprae-specific repetitive sequence RLEP was detected by PCR amplification in purified DNA extracted from armadillo spleen and liver tissue samples. A positive RLEP signal was confirmed in 62% of the armadillos (10/16), indicating high rates of infection with M. leprae. Immunohistochemistry of sections of infected armadillo spleens revealed mycobacterial DNA and cell wall constituents in situ detected by SYBR Gold and auramine/rhodamine staining techniques, respectively. The M. leprae-specific antigen, phenolic glycolipid I (PGL-I) was detected in spleen sections using a rabbit polyclonal antibody specific for PGL-I. Anti-PGL-I titers were assessed by ELISA in sera from 146 inhabitants of Belterra, a hyperendemic city located in western Pará state in Brazil. A positive anti-PGL-I titer is a known biomarker for M. leprae infection in both humans and armadillos. Individuals who consumed armadillo meat most frequently (more than once per month) showed a significantly higher anti-PGL-I titer than those who did not eat or ate less frequently than once per month. Armadillos infected with M. leprae represent a potential environmental reservoir. Consequently, people who hunt, kill, or process or eat armadillo meat are at a higher risk for infection with M. leprae from these animals.

Schistosomiasis in Africa: Improving strategies for long-term and sustainable morbidity control

28 June 2018 - 9:00pm

by Michael D. French, Darin Evans, Fiona M. Fleming, W. Evan Secor, Nana-Kwadwo Biritwum, Simon J. Brooker, Amaya Bustinduy, Anouk Gouvras, Narcis Kabatereine, Charles H. King, Maria Rebollo Polo, Jutta Reinhard-Rupp, David Rollinson, Louis-Albert Tchuem Tchuenté, Jürg Utzinger, Johannes Waltz, Yaobi Zhang

Meteorological factors and risk of hemorrhagic fever with renal syndrome in Guangzhou, southern China, 2006–2015

27 June 2018 - 9:00pm

by Yuehong Wei, Yang Wang, Xiaoning Li, Pengzhe Qin, Ying Lu, Jianmin Xu, Shouyi Chen, Meixia Li, Zhicong Yang

Background

The epidemic tendency of hemorrhagic fever with renal syndrome (HFRS) is on the rise in recent years in Guangzhou. This study aimed to explore the associations between meteorological factors and HFRS epidemic risk in Guangzhou for the period from 2006–2015.

Methods

We obtained data of HFRS cases in Guangzhou from the National Notifiable Disease Report System (NNDRS) during the period of 2006–2015. Meteorological data were obtained from the Guangzhou Meteorological Bureau. A negative binomial multivariable regression was used to explore the relationship between meteorological variables and HFRS.

Results

The annual average incidence was 0.92 per 100000, with the annual incidence ranging from 0.64/100000 in 2009 to 1.05/100000 in 2012. The monthly number of HFRS cases decreased by 5.543% (95%CI -5.564% to -5.523%) each time the temperature was increased by 1°C and the number of cases decreased by 0.075% (95%CI -0.076% to -0.074%) each time the aggregate rainfall was increased by 1 mm. We found that average temperature with a one-month lag was significantly associated with HFRS transmission.

Conclusions

Meteorological factors had significant association with occurrence of HFRS in Guangzhou, Southern China. This study provides preliminary information for further studies on epidemiological prediction of HFRS and for developing an early warning system.

Multi locus sequence typing of <i>Burkholderia pseudomallei</i> isolates from India unveils molecular diversity and confers regional association in Southeast Asia

27 June 2018 - 9:00pm

by Veeraraghavan Balaji, Susmitha Perumalla, Rajamani Perumal, Francis Yesurajan Inbanathan, Suresh Kumar Rajamani Sekar, Miracle Magdelene Paul, Rani Diana Sahni, John Antony Jude Prakash, Ramya Iyadurai

Objectives

Burkholderia pseudomallei, the causative agent for melioidosis, has become a public health problem in India and across the world. Melioidosis can be difficult to diagnose because of the inconsistent clinical presentations of the disease. This study aims to determine the genetic diversity among the clinical isolates of B. pseudomaelli from India in order to establish a molecular epidemiology and elucidate the Southeast Asian association.

Methods

Molecular typing using multi locus sequence typing was performed on thirty one archived B. pseudomallei clinical isolates, previously characterised from specimens obtained from patients admitted to the Christian Medical College & Hospital, Vellore from 2015 to 2016. Further investigations into the genetic heterogeneity and evolution at a regional and global level were performed using insilico tools.

Results

Multi locus sequence typing (MLST) of the isolates from systemic and localized forms of melioidosis, including blood, pus, tissue, and urine specimens, revealed twenty isolates with novel sequence types and eleven with previously reported sequence types. High genetic diversity was observed using MLST with a strong association within the Southeast Asian region.

Conclusions

Molecular typing of B. pseudomallei clinical isolates using MLST revealed high genetic diversity and provided a baseline molecular epidemiology of the disease in India with a strong Southeast Asian association of the strains. Future studies should focus on whole genome based Single-Nucleotide-Polymorphism (SNP) which has the advantage of a high discriminatory power, to further understand the novel sequence types reported in this study.

A cluster of cases of severe fever with thrombocytopenia syndrome bunyavirus infection in China, 1996: A retrospective serological study

25 June 2018 - 9:00pm

by Jianli Hu, Chao Shi, Zhifeng Li, Xiling Guo, Yanhua Qian, Wenwen Tan, Xian Li, Xian Qi, Xiaoju Su, Minghao Zhou, Hua Wang, Yongjun Jiao, Changjun Bao

Background

A cluster of eleven patients, including eight family members and three healthcare workers with fever and thrombocytopenia occurred in Yixing County, Jiangsu Province, China, from October to November 1996. However, the initial investigation failed to identify its etiology. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS bunyavirus (SFTSV), which was first discovered in 2009. The discovery of novel SFTSV resulted in our consideration to test SFTSV on the remaining samples of this cluster in September 2010.

Methodology/Principal findings

We retrospectively analyzed the epidemiological and clinical data of this cluster. The first case, one 55-year-old man with fulminant hemorrhagic diseases, died on October 14, 1996. His younger brother (the second case) developed similar hemorrhagic diseases after nursing him and then died on November 3. From November 4 to November 15, nine other patients, including six family members and three medical staffs, developed fever and thrombocytopenia after exposure to the second case. The sera of six patients were collected on November 24, 1996. IgM antibodies against SFTSV were detected in all of the six patients’ sera using enzyme-linked immunosorbent assay (ELISA), while IgG antibodies were detected in one patient’s serum using an indirect immunofluorescence assay (IFA). We also found that IgG antibodies against SFTSV were still detected in four surviving patients’ sera 14 years after illness onset.

Conclusions and significance

The mysterious pathogen of the cluster in 1996 was proved to be SFTSV on the basis of its epidemiological data, clinical data and serological results. It suggests that SFTSV has been circulating in China for more than 10 years before being identified in 2009, and SFTSV IgG antibodies can persist for up to 14 years.

Low prevalence of HTLV1/2 infection in a population of immigrants living in southern Italy

25 June 2018 - 9:00pm

by Loredana Alessio, Carmine Minichini, Mario Starace, Laura Occhiello, Mara Caroprese, Giovanni Di Caprio, Caterina Sagnelli, Luciano Gualdieri, Mariantonietta Pisaturo, Lorenzo Onorato, Gaetano Scotto, Margherita Macera, Stefania De Pascalis, Evangelista Sagnelli, Nicola Coppola

Aims

To assess the prevalence of HTLV-1 and HTLV-2 infections in a cohort of immigrants living in southern Italy.

Findings

We screened for antibody to HTLV-1/2 infection 1,498 consecutive immigrants born in endemic areas (sub-Saharan Africa or southern-Asia) by a commercial chemiluminescent microparticle immunoassay. If confirmed in a Western blot assay, which differentiates anti-HTLV-1 from anti-HTLV-2, the positive sera were tested for specific HTLV RNA by a home-made PCR. The immigrants investigated were more frequently males (89.05%), young (median age 26 years), with a low level of education (median schooling 6 years), born in sub-Saharan Africa (79.70%). They had been living in Italy for a median period of 5 months. Only one (0.07%) subject was anti-HTLV-1 -positive/HTLV-1 RNA-negative; he was an asymptomatic 27-year-old male from Nigeria with 6 years’ schooling who stated unsafe sexual habits and unsafe injection therapy.

Conclusions

The data suggest screening for HTLV1 and HTLV-2 infections all blood donors to Italy from endemic countries at least on their first donation; however, a cost-effectiveness study is needed to clarify this topic.

Seroposotivity of <i>Brucella</i> spp. and <i>Leptospira</i> spp. antibodies among abattoir workers and meat vendors in the city of Mwanza, Tanzania: A call for one health approach control strategies

25 June 2018 - 9:00pm

by Mariam M. Mirambo, Georgies F. Mgode, Zakaria O. Malima, Matata John, Elifuraha B. Mngumi, Ginethon G. Mhamphi, Stephen E. Mshana

Introduction

Brucellosis and leptospirosis are among neglected tropical zoonotic diseases particularly in the resource limited countries. Despite being endemic in these countries, there is paucity of information on its magnitude. This study investigated seropositivity of Brucella spp. and Leptospira spp., and associated factors among abattoir workers and meat vendors in the city of Mwanza, Tanzania.

Methodology

A community based cross-sectional study was conducted in Mwanza city from May to July 2017. Socio-demographic and other relevant information were collected. Detection of Brucella spp. and Leptospira spp. antibodies were done using slide agglutination test and microscopic agglutination test, respectively. Data were analyzed using STATA version 13 Software.

Findings

A total of 250 participants (146 abattoir workers and 104 meat vendors) were enrolled with median age of 31 (IQR: 25–38) years. The overall, seropositivity of Brucella spp. antibodies was 48.4% (95% Cl: 42–54). Seropositivity of B. abortus was significantly higher than that of B. melitensis (46.0%, 95%Cl: 39–52 vs. 23.6%, 95% Cl: 18–28, P<0.001) while seropositivity of both species was 21.2% (95%Cl: 16–26). The seropositivity of Leptospira spp. was 10.0% (95% CI: 6–13) with predominance of Leptospira kirschneri serovar Sokoine which was detected in 7.2% of the participants. Being abattoir worker (OR: 2.19, 95% CI 1.06–4.54, p = 0.035) and long work duration (OR: 1.06, 95%CI: 1.01–1.11, p = 0.014) predicted presence of both B.abortus and B. melitensis antibodies. Only being married (p = 0.041) was significantly associated with seropositivity of Leptospira spp. Primary education was the only factor independently predicted presence of Brucella spp. antibodies among abattoir workers on sub-analysis of occupational exposure. None of factors were found to be associated with presence of Brucella spp. antibodies among meat vendors on sub-analysis.

Conclusion

Seropositivity of B.abortus antibodies among abattoir workers and meat vendors is high and seem to be a function of being abattoir worker, having worked for long duration in the abattoir and having primary education. In addition, a significant proportion of abattoir workers and meat vendors in the city was seropositive for Leptospira kirschneri serovar Sokoine. There is a need to consider ‘one health approach’ in devising appropriate strategies to control these diseases in the developing countries.

Integrated approach in the control and management of skin neglected tropical diseases in Lalo, Benin

25 June 2018 - 9:00pm

by Yves Thierry Barogui, Gabriel Diez, Esai Anagonou, Roch Christian Johnson, Inès Cica Gomido, Hermione Amoukpo, Zoulkifl Salou Bachirou, Jean Gabin Houezo, Raoul Saizonou, Ghislain Emmanuel Sopoh, Asiedu Kingsley

Background

Neglected Tropical Diseases (NTDs) are a group of several communicable diseases prevalent in the tropical and subtropical areas. The co-endemicity of these diseases, the similarity of the clinical signs, and need to maximize limited financial and human resources have necessitated implementation of integrated approach. Our study aims to share the lessons of this integrated approach in the fight against Buruli ulcer (BU), leprosy and yaws in a rural district in Benin.

Method

It is a cross-sectional study using a single set of activities data conducted from May 2016 to December 2016. Health workers and community health volunteers involved in this study were trained on integrated approach of the Buruli ulcer, leprosy and yaws. Village chiefs were briefed about the activity. The trained team visited the villages and schools in the district of Lalo in Benin. After the education and awareness raising sessions, all persons with a skin lesion who presented voluntarily to the team were carefully examined in a well-lit area which respected their privacy. Suspected cases were tested as needed. The socio-demographic information and the characteristics of the lesions were collected using a form. A descriptive analysis of the epidemiological, clinical and laboratory variables of the cases was made using Excel 2013 and SPSS version 22.00.

Principal findings

In the study period, 1106 people were examined. The median (IQR) age of those examined was 11 (8; 27) years. Of 34 (3.1%) suspected BU cases, 15 (1.4%) were confirmed by PCR. Only three cases of leprosy were confirmed. The 185 (16.7%) suspected cases of yaws were all negative with the rapid test. The majority of cases were other skin conditions, including fungal infections, eczema and traumatic lesions.

Conclusion

The integrated approach of skin NTD allows optimal use of resources and surveillance of these diseases. Sustaining this skin NTD integrated control will require the training of peripheral health workers not only on skin NTD but also on basic dermatology.

Genetic diversity and spatial-temporal distribution of <i>Yersinia pestis</i> in Qinghai Plateau, China

25 June 2018 - 9:00pm

by Xiaoqing Xu, Yujun Cui, Youquan Xin, Xiaoyan Yang, Qingwen Zhang, Yong Jin, Haihong Zhao, Jian He, Xing Jin, Cunxiang Li, Juan Jin, Xiang Li, Haisheng Wu, Zhizhen Qi

Background

Plague, caused by the bacterium Yersinia pestis, is a highly infectious, zoonotic disease. Hundreds of human plague cases are reported across the world annually. Qinghai Plateau is one of the most severely affected plague regions in China, with more than 240 fatal cases of Y. pestis in the last 60 years. Conventional epidemiologic analysis has effectively guided the prevention and control of local plague transmission; however, molecular genetic analysis is more effective for investigating population diversity and transmission. In this report, we employed different genetic markers to analyze the population structure of Y. pestis in Qinghai Plateau.

Methodology/Principal finding

We employed a two-step hierarchical strategy to analyze the phylogeny of 102 Qinghai Plateau isolates of Y. pestis, collected between 1954 and 2011. First, we defined the genealogy of Y. pestis by constructed minimum spanning tree based on 25 key SNPs. Seven groups were identifi7ed, with group 1.IN2 being identified as the dominant population. Second, two methods, MLVA and CRISPR, were applied to examine the phylogenetic detail of group 1.IN2, which was further divided into three subgroups. Subgroups of 1.IN2 revealed a clear geographic cluster, possibly associated with interaction between bacteriophage and Y. pestis. More recently, Y. pestis populations appear to have shifted from the east toward the center and west of Qinghai Plateau. This shift could be related to destruction of the local niche of the original plague focus through human activities. Additionally, we found that the abundance and relative proportion of 1.IN2 subgroups varied by decade and might be responsible for the fluctuations of plague epidemics in Qinghai Plateau.

Conclusion/Significance

Molecular genotyping methods provided us with detailed information on population diversity and the spatial-temporal distribution of dominant populations of Y. pestis, which will facilitate future surveillance, prevention, and control of plague in Qinghai Plateau.

Forecasting the effectiveness of indoor residual spraying for reducing dengue burden

25 June 2018 - 9:00pm

by Thomas J. Hladish, Carl A. B. Pearson, Diana Patricia Rojas, Hector Gomez-Dantes, M. Elizabeth Halloran, Gonzalo M. Vazquez-Prokopec, Ira M. Longini

Background

Historically, mosquito control programs successfully helped contain malaria and yellow fever, but recent efforts have been unable to halt the spread of dengue, chikungunya, or Zika, all transmitted by Aedes mosquitoes. Using a dengue transmission model and results from indoor residual spraying (IRS) field experiments, we investigated how IRS-like campaign scenarios could effectively control dengue in an endemic setting.

Methods and findings

In our model, we found that high levels of household coverage (75% treated once per year), applied proactively before the typical dengue season could reduce symptomatic infections by 89.7% (median of 1000 simulations; interquartile range [IQR]:[83.0%, 94.8%]) in year one and 78.2% (IQR: [71.2%, 88.0%]) cumulatively over the first five years of an annual program. Lower coverage had correspondingly lower effectiveness, as did reactive campaigns. Though less effective than preventative campaigns, reactive and even post-epidemic interventions retain some effectiveness; these campaigns disrupt inter-seasonal transmission, highlighting an off-season control opportunity. Regardless, none of the campaign scenarios maintain their initial effectiveness beyond two seasons, instead stabilizing at much lower levels of benefit: in year 20, median effectiveness was only 27.3% (IQR: [-21.3%, 56.6%]). Furthermore, simply ceasing an initially successful program exposes a population with lowered herd immunity to the same historical threat, and we observed outbreaks more than four-fold larger than pre-intervention outbreaks. These results do not take into account evolving insecticide resistance, thus long-term effectiveness may be lower if new, efficacious insecticides are not developed.

Conclusions

Using a detailed agent-based dengue transmission model for Yucatán State, Mexico, we predict that high coverage indoor residual spraying (IRS) interventions can largely eliminate transmission for a few years, when applied a few months before the typical seasonal epidemic peak. However, vector control succeeds by preventing infections, which precludes natural immunization. Thus, as a population benefits from mosquito control, it gradually loses naturally acquired herd immunity, and the control effectiveness declines; this occurs across all of our modeled scenarios, and is consistent with other empirical work. Long term control that maintains early effectiveness would require some combination of increasing investment, complementary interventions such as vaccination, and control programs across a broad region to diminish risk of importation.

Polymorphisms and haplotypes in the promoter of the TNF-α gene are associated with disease severity of severe fever with thrombocytopenia syndrome in Chinese Han population

25 June 2018 - 9:00pm

by Bo Xing, Xiao-Kun Li, Shao-Fei Zhang, Qing-Bin Lu, Juan Du, Pan-He Zhang, Zhen-Dong Yang, Ning Cui, Chen-Tao Guo, Wu-Chun Cao, Xiao-Ai Zhang, Wei Liu

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is caused by a novel bunyavirus, SFTSV. We assessed whether the single nucleotide polymorphisms (SNPs) in the tumor necrosis factor-alpha (TNF-α) were associated with risk to severity of SFTS. Five TNF-α SNPs (SNP1: T-1031C; SNP2: C-863A; SNP3: C-857T; SNP4: G-308A; SNP5: G-238A) were genotyped in 987 hospitalized SFTS patients and 633 asymptomatic/mild SFTSV-infected subjects of Chinese Han origin. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). The hospitalized SFTS patients had significantly lower frequency of G-238A A allele than those with mild/asymptomatic infection (P = 0.006). Furthermore, T-1031C C allele (P < 0.001) and G-238A A allele (P < 0.001) were significantly associated with decreased risk of death. Multiple haplotypes were significantly associated with decreased risk of SFTS hospital admission (SNP1-2, CC; SNP1-3, CCC; SNP1-4, CCCG; SNP1-5, CCCGA; SNP2-4, CCGA; SNP3-5, CGA; SNP4-5, GA) and death (SNP1-2, CA; SNP1-3, CAG; SNP1-4, CACG; SNP1-5, CACGG; SNP2-3, AC; SNP2-4, ACG; SNP2-5, ACGG) after correction for multiple comparisons. By using the ELISA assay, we observed that TNF-α concentration of hospitalized patients was significantly increased in acute phase than in convalescent phase (P < 0.001). Elevated TNF-α concentration was also revealed from fatal patients (P < 0.001). The -238A allele was associated with decreased serum TNF-α levels in SFTS patients in acute phase (P = 0.01). Our findings suggest that polymorphisms in TNF-α gene may play a role in mediating the risk to disease severity of SFTS in Chinese Han population.

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