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Decline in infection-related morbidities following drug-mediated reductions in the intensity of <i>Schistosoma</i> infection: A systematic review and meta-analysis
by Gisele Andrade, David J. Bertsch, Andrea Gazzinelli, Charles H. KingBackground
Since 1984, WHO has endorsed drug treatment to reduce Schistosoma infection and its consequent morbidity. Cross-sectional studies suggest pre-treatment correlation between infection intensity and risk for Schistosoma-related pathology. However, evidence also suggests that post-treatment reduction in intensity may not reverse morbidity because some morbidities occur at all levels of infection, and some reflect permanent tissue damage. The aim of this project was to systematically review evidence on drug-based control of schistosomiasis and to develop a quantitative estimate of the impact of post-treatment reductions in infection intensity on prevalence of infection-associated morbidity.Methodology/Principal findings
This review was registered at inception with PROSPERO (CRD42015026080). Studies that evaluated morbidity before and after treatment were identified by online searches and searches of private archives. Post-treatment odds ratios or standardized mean differences were calculated for each outcome, and these were correlated to treatment-related egg count reduction ratios (ERRs) by meta-regression. A greater ERR correlated with greater reduction in odds of most morbidities. Random effects meta-analysis was used to derive summary estimates: after treatment of S. mansoni and S. japonicum, left-sided hepatomegaly was reduced by 54%, right-sided hepatomegaly by 47%, splenomegaly by 37%, periportal fibrosis by 52%, diarrhea by 53%, and blood in stools by 75%. For S. haematobium, hematuria was reduced by 92%, proteinuria by 90%, bladder lesions by 86%, and upper urinary tract lesions by 72%. There were no consistent changes in portal dilation or hemoglobin levels. In sub-group analysis, age, infection status, region, parasite species, and interval to follow-up were associated with meaningful differences in outcome.Conclusion/Significance
While there are challenges to implementing therapy for schistosomiasis, and praziquantel therapy is not fully curative, reductions in egg output are significantly correlated with decreased morbidity and can be used to project diminution in disease burden when contemplating more aggressive strategies to minimize infection intensity.
by Lian F. Thomas, William A. de Glanville, Elizabeth A. J. Cook, Barend M. De C. Bronsvoort, Ian Handel, Claire N. Wamae, Samuel Kariuki, Eric M. FèvreThe tapeworm Taenia solium is the parasite responsible for neurocysticercosis, a neglected tropical disease of public health importance, thought to cause approximately 1/3 of epilepsy cases across endemic regions. The consumption of undercooked infected pork perpetuates the parasite’s life-cycle through the establishment of adult tapeworm infections in the community. Reducing the risk associated with pork consumption in the developing world is therefore a public health priority. The aim of this study was to estimate the risk of any one pork meal in western Kenya containing a potentially infective T. solium cysticercus at the point of consumption, an aspect of the parasite transmission that has not been estimated before. To estimate this, we used a quantitative food chain risk assessment model built in the @RISK add-on to Microsoft Excel. This model indicates that any one pork meal consumed in western Kenya has a 0.006 (99% Uncertainty Interval (U.I). 0.0002–0.0164) probability of containing at least one viable T. solium cysticercus at the point of consumption and therefore being potentially infectious to humans. This equates to 22,282 (99% U.I. 622–64,134) potentially infective pork meals consumed in the course of one year within Busia District alone. This model indicates a high risk of T. solium infection associated with pork consumption in western Kenya and the work presented here can be built upon to investigate the efficacy of various mitigation strategies for this locality.
Distribution and abundance of key vectors of Rift Valley fever and other arboviruses in two ecologically distinct counties in Kenya
by Rosemary Sang, Samwel Arum, Edith Chepkorir, Gladys Mosomtai, Caroline Tigoi, Faith Sigei, Olivia Wesula Lwande, Tobias Landmann, Hippolyte Affognon, Clas Ahlm, Magnus EvanderBackground
Rift Valley fever (RVF) is a mosquito-borne viral zoonosis of ruminants and humans that causes outbreaks in Africa and the Arabian Peninsula with significant public health and economic consequences. Humans become infected through mosquito bites and contact with infected livestock. The virus is maintained between outbreaks through vertically infected eggs of the primary vectors of Aedes species which emerge following rains with extensive flooding. Infected female mosquitoes initiate transmission among nearby animals, which amplifies virus, thereby infecting more mosquitoes and moving the virus beyond the initial point of emergence. With each successive outbreak, RVF has been found to expand its geographic distribution to new areas, possibly driven by available vectors. The aim of the present study was to determine if RVF virus (RVFV) transmission risk in two different ecological zones in Kenya could be assessed by looking at the species composition, abundance and distribution of key primary and secondary vector species and the level of virus activity.Methodology
Mosquitoes were trapped during short and long rainy seasons in 2014 and 2015 using CO2 baited CDC light traps in two counties which differ in RVF epidemic risk levels(high risk Tana-River and low risk Isiolo),cryo-preserved in liquid nitrogen, transported to the laboratory, and identified to species. Mosquito pools were analyzed for virus infection using cell culture screening and molecular analysis.Findings
Over 69,000 mosquitoes were sampled and identified as 40 different species belonging to 6 genera (Aedes, Anopheles, Mansonia, Culex, Aedeomyia, Coquillettidia). The presence and abundance of Aedes mcintoshi and Aedes ochraceus, the primary mosquito vectors associated with RVFV transmission in outbreaks, varied significantly between Tana-River and Isiolo. Ae. mcintoshi was abundant in Tana-River and Isiolo but notably, Aedes ochraceus found in relatively high numbers in Tana-River (n = 1,290), was totally absent in all Isiolo sites. Fourteen virus isolates including Sindbis, Bunyamwera, and West Nile fever viruses were isolated mostly from Ae. mcintoshi sampled in Tana-River. RVFV was not detected in any of the mosquitoes.Conclusion
This study presents the geographic distribution and abundance of arbovirus vectors in two Kenyan counties, which may assist with risk assessment for mosquito borne diseases.
Partnering for impact: Integrated transmission assessment surveys for lymphatic filariasis, soil transmitted helminths and malaria in Haiti
by Alaine Kathryn Knipes, Jean Frantz Lemoine, Franck Monestime, Carl R. Fayette, Abdel N. Direny, Luccene Desir, Valery E. Beau de Rochars, Thomas G. Streit, Kristen Renneker, Brian K. Chu, Michelle A. Chang, Kimberly E. Mace, Kimberly Y. Won, Patrick J. LammieBackground
Since 2001, Haiti’s National Program for the Elimination of Lymphatic Filariasis (NPELF) has worked to reduce the transmission of LF through annual mass drug administration with diethylcarbamazine and albendazole. The NPELF reached full national coverage with MDA for LF in 2012, and by 2014, a total of 14 evaluation units (48 communes) had met WHO eligibility criteria to conduct LF transmission assessment surveys (TAS) to determine whether prevalence had been reduced to below a threshold, such that transmission is assumed to be no longer sustainable. Haiti is also endemic for malaria and many communities suffer a high burden of soil transmitted helminths (STH). Heeding the call from WHO for integration of neglected tropical diseases (NTD) activities, Haiti’s NPELF worked with the national malaria control program (NMCP) and with partners to develop an integrated TAS (LF-STH-malaria) to include assessments for malaria and STH.Methodology/Principle findings
The aim of this study was to evaluate the feasibility of using TAS surveys for LF as a platform to collect information about STH and malaria. Between November 2014 and June 2015, TAS were conducted in 14 evaluation units (EUs) including 1 TAS (LF-only), 1 TAS-STH-malaria, and 12 TAS-malaria, with a total of 16,655 children tested for LF, 14,795 tested for malaria, and 298 tested for STH. In all, 12 of the 14 EUs passed the LF TAS, allowing the program to stop MDA for LF in 44 communes. The EU where children were also tested for STH will require annual school-based treatment for STH to maintain reduced STH levels. Finally, only 12 of 14,795 children tested positive for malaria by RDT in 38 communes.Conclusions/Significance
Haiti’s 2014–2015 Integrated TAS surveys provide evidence of the feasibility of using the LF TAS as a platform for integration of assessments for STH and or malaria.
The One Health approach to identify knowledge, attitudes and practices that affect community involvement in the control of Rift Valley fever outbreaks
by Osama Ahmed Hassan, Hippolyte Affognon, Joacim Rocklöv, Peter Mburu, Rosemary Sang, Clas Ahlm, Magnus EvanderRift Valley fever (RVF) is a viral mosquito-borne disease with the potential for global expansion, causes hemorrhagic fever, and has a high case fatality rate in young animals and in humans. Using a cross-sectional community-based study design, we investigated the knowledge, attitudes and practices of people living in small village in Sudan with respect to RVF outbreaks. A special One Health questionnaire was developed to compile data from 235 heads of household concerning their knowledge, attitudes, and practices with regard to controlling RVF. Although the 2007 RVF outbreak in Sudan had negatively affected the participants’ food availability and livestock income, the participants did not fully understand how to identify RVF symptoms and risk factors for both humans and livestock. For example, the participants mistakenly believed that avoiding livestock that had suffered spontaneous abortions was the least important risk factor for RVF. Although the majority noticed an increase in mosquito population during the 2007 RVF outbreak, few used impregnated bed nets as preventive measures. The community was reluctant to notify the authorities about RVF suspicion in livestock, a sentinel for human RVF infection. Almost all the respondents stressed that they would not receive any compensation for their dead livestock if they notified the authorities. In addition, the participants believed that controlling RVF outbreaks was mainly the responsibility of human health authorities rather than veterinary authorities. The majority of the participants were aware that RVF could spread from one region to another within the country. Participants received most their information about RVF from social networks and the mass media, rather than the health system or veterinarians. Because the perceived role of the community in controlling RVF was fragmented, the probability of RVF spread increased.
by Francois Peyron, Rima Mc Leod, Daniel Ajzenberg, Despina Contopoulos-Ioannidis, François Kieffer, Laurent Mandelbrot, L. David Sibley, Hervé Pelloux, Isabelle Villena, Martine Wallon, Jose G. Montoya
by Periklis Panagopoulos, Vasileios Mitsopoulos, Antonios Papadopoulos, Spyridoula Theodorou, Chrysoula Christodoulaki, Kyriakos Aloupogiannis, Nikolaos Papantoniou
Correction: MLST-Based Population Genetic Analysis in a Global Context Reveals Clonality amongst <i>Cryptococcus neoformans</i> var. <i>grubii</i> VNI Isolates from HIV Patients in Southeastern Brazil
by The PLOS Neglected Tropical Diseases Staff
by Bourama Traoré, Fabiano Oliveira, Ousmane Faye, Adama Dicko, Cheick A. Coulibaly, Ibrahim M. Sissoko, Samake Sibiry, Nafomon Sogoba, Moussa Brema Sangare, Yaya I. Coulibaly, Pierre Traore, Sekou F. Traore, Jennifer M. Anderson, Somita Keita, Jesus G. Valenzuela, Shaden Kamhawi, Seydou Doumbia
Comparative and functional triatomine genomics reveals reductions and expansions in insecticide resistance-related gene families
by Lucila Traverso, Andrés Lavore, Ivana Sierra, Victorio Palacio, Jesús Martinez-Barnetche, José Manuel Latorre-Estivalis, Gaston Mougabure-Cueto, Flavio Francini, Marcelo G. Lorenzo, Mario Henry Rodríguez, Sheila Ons, Rolando V. Rivera-PomarBackground
Triatomine insects are vectors of Trypanosoma cruzi, a protozoan parasite that is the causative agent of Chagas’ disease. This is a neglected disease affecting approximately 8 million people in Latin America. The existence of diverse pyrethroid resistant populations of at least two species demonstrates the potential of triatomines to develop high levels of insecticide resistance. Therefore, the incorporation of strategies for resistance management is a main concern for vector control programs. Three enzymatic superfamilies are thought to mediate xenobiotic detoxification and resistance: Glutathione Transferases (GSTs), Cytochromes P450 (CYPs) and Carboxyl/Cholinesterases (CCEs). Improving our knowledge of key triatomine detoxification enzymes will strengthen our understanding of insecticide resistance processes in vectors of Chagas’ disease.Methods and findings
The discovery and description of detoxification gene superfamilies in normalized transcriptomes of three triatomine species: Triatoma dimidiata, Triatoma infestans and Triatoma pallidipennis is presented. Furthermore, a comparative analysis of these superfamilies among the triatomine transcriptomes and the genome of Rhodnius prolixus, also a triatomine vector of Chagas’ disease, and other well-studied insect genomes was performed. The expression pattern of detoxification genes in R. prolixus transcriptomes from key organs was analyzed. The comparisons reveal gene expansions in Sigma class GSTs, CYP3 in CYP superfamily and clade E in CCE superfamily. Moreover, several CYP families identified in these triatomines have not yet been described in other insects. Conversely, several groups of insecticide resistance related enzymes within each enzyme superfamily are reduced or lacking in triatomines. Furthermore, our qRT-PCR results showed an increase in the expression of a CYP4 gene in a T. infestans population resistant to pyrethroids. These results could point to an involvement of metabolic detoxification mechanisms on the high levels of pyrethroid resistance detected in triatomines from the Gran Chaco ecoregion.Conclusions and significance
Our results help to elucidate the potential insecticide resistance mechanisms in vectors of Chagas’ disease and provide new relevant information for this field. This study shows that metabolic resistance might be a contributing cause of the high pyrethroid resistance observed in wild T. infestans populations from the Gran Chaco ecoregion, area in which although subjected to intense pyrethroid treatments, vector control has failed. This study opens new avenues for further functional studies on triatomine detoxification mechanisms.
Species dependent impact of helminth-derived antigens on human macrophages infected with <i>Mycobacterium tuberculosis</i>: Direct effect on the innate anti-mycobacterial response
by Naomi Aira, Anna-Maria Andersson, Susmita K. Singh, Derek M. McKay, Robert BlomgranBackground
In countries with a high prevalence of tuberculosis there is high coincident of helminth infections that might worsen disease outcome. While Mycobacterium tuberculosis (Mtb) gives rise to a pro-inflammatory Th1 response, a Th2 response is typical of helminth infections. A strong Th2 response has been associated with decreased protection against tuberculosis.Principal findings
We investigated the direct effect of helminth-derived antigens on human macrophages, hypothesizing that helminths would render macrophages less capable of controlling Mtb. Measuring cytokine output, macrophage surface markers with flow cytometry, and assessing bacterial replication and phagosomal maturation revealed that antigens from different species of helminth directly affect macrophage responses to Mtb. Antigens from the tapeworm Hymenolepis diminuta and the nematode Trichuris muris caused an anti-inflammatory response with M2-type polarization, reduced macrophage phagosome maturation and ability to activate T cells, along with increased Mtb burden, especially in T. muris exposed cells which also induced the highest IL-10 production upon co-infection. However, antigens from the trematode Schistosoma mansoni had the opposite effect causing a decrease in IL-10 production, M1-type polarization and increased control of Mtb.Conclusion
We conclude that, independent of any adaptive immune response, infection with helminth parasites, in a species-specific manner can influence the outcome of tuberculosis by either enhancing or diminishing the bactericidal function of macrophages.
Comparative genome analysis of VSP-II and SNPs reveals heterogenic variation in contemporary strains of <i>Vibrio cholerae</i> O1 isolated from cholera patients in Kolkata, India
by Daisuke Imamura, Masatomo Morita, Tsuyoshi Sekizuka, Tamaki Mizuno, Taichiro Takemura, Tetsu Yamashiro, Goutam Chowdhury, Gururaja P. Pazhani, Asish K. Mukhopadhyay, Thandavarayan Ramamurthy, Shin-ichi Miyoshi, Makoto Kuroda, Sumio Shinoda, Makoto OhnishiCholera is an acute diarrheal disease and a major public health problem in many developing countries in Asia, Africa, and Latin America. Since the Bay of Bengal is considered the epicenter for the seventh cholera pandemic, it is important to understand the genetic dynamism of Vibrio cholerae from Kolkata, as a representative of the Bengal region. We analyzed whole genome sequence data of V. cholerae O1 isolated from cholera patients in Kolkata, India, from 2007 to 2014 and identified the heterogeneous genomic region in these strains. In addition, we carried out a phylogenetic analysis based on the whole genome single nucleotide polymorphisms to determine the genetic lineage of strains in Kolkata. This analysis revealed the heterogeneity of the Vibrio seventh pandemic island (VSP)-II in Kolkata strains. The ctxB genotype was also heterogeneous and was highly related to VSP-II types. In addition, phylogenetic analysis revealed the shifts in predominant strains in Kolkata. Two distinct lineages, 1 and 2, were found between 2007 and 2010. However, the proportion changed markedly in 2010 and lineage 2 strains were predominant thereafter. Lineage 2 can be divided into four sublineages, I, II, III and IV. The results of this study indicate that lineages 1 and 2-I were concurrently prevalent between 2007 and 2009, and lineage 2-III observed in 2010, followed by the predominance of lineage 2-IV in 2011 and continued until 2014. Our findings demonstrate that the epidemic of cholera in Kolkata was caused by several distinct strains that have been constantly changing within the genetic lineages of V. cholerae O1 in recent years.
Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the <i>Na</i>-GST-1/Alhydrogel hookworm vaccine
by Jill B. Brelsford, Jordan L. Plieskatt, Anna Yakovleva, Amar Jariwala, Brian P. Keegan, Jin Peng, Pengjun Xia, Guangzhao Li, Doreen Campbell, Maria Victoria Periago, Rodrigo Correa-Oliveira, Maria Elena Bottazzi, Peter J. Hotez, David Diemert, Jeffrey M. BethonyA new generation of vaccines for the neglected tropical diseases (NTDs) have now advanced into clinical development, with the Na-GST-1/Alhydrogel Hookworm Vaccine already being tested in Phase 1 studies in healthy adults. The current manuscript focuses on the often overlooked critical aspects of NTD vaccine product development, more specifically, vaccine stability testing programs. A key measure of vaccine stability testing is "relative potency" or the immunogenicity of the vaccine during storage. As with most NTD vaccines, the Na-GST-1/Alhydrogel Hookworm Vaccine was not developed by attenuation or inactivation of the pathogen (Necator americanus), so conventional methods for measuring relative potency are not relevant for this investigational product. Herein, we describe a novel relative potency testing program and report for the first time on the clinical lot of this NTD vaccine during its first 60 months of storage at 2–8°C. We also describe the development of a complementary functional assay that measures the ability of IgG from animals or humans immunized with Na-GST-1/Alhydrogel to neutralize this important hookworm enzyme. While 90% inhibition of the catalytic activity of Na-GST-1 was achieved in animals immunized with Na-GST-1/Alhydrogel, lower levels of inhibition were observed in immunized humans. Moreover, anti-Na-GST-1 antibodies from volunteers in non-hookworm endemic areas were better able to inhibit catalytic activity than anti-Na-GST-1 antibodies from volunteers resident in hookworm endemic areas. The results described herein provide the critical tools for the product development of NTD vaccines.
by Mauricio Lisboa Nobre, Ximena Illarramendi, Kathryn Margaret Dupnik, Mariana de Andrea Hacker, José Augusto da Costa Nery, Selma Maria Bezerra Jerônimo, Euzenir Nunes SarnoBackground
Leprosy remains an important public health problem in Brazil where 28,761 new cases were diagnosed in 2015, the second highest number of new cases detected globally. The disease is caused by Mycobacterium leprae, a pathogen spread by patients with multibacillary (MB) leprosy. This study was designed to identify population groups most at risk for MB disease in Brazil, contributing to new ideas for early diagnosis and leprosy control.Methods
A national databank of cases reported in Brazil (2001–2013) was used to evaluate epidemiological characteristics of MB leprosy. Additionally, the databank of a leprosy reference center was used to determine factors associated with higher bacillary loads.Results
A total of 541,090 cases were analyzed. New case detection rates (NCDRs) increased with age, especially for men with MB leprosy, reaching 44.8 new cases/100,000 population in 65–69 year olds. Males and subjects older than 59 years had twice the odds of MB leprosy than females and younger cases (OR = 2.36, CI95% = 2.33–2.38; OR = 1.99, CI95% = 1.96–2.02, respectively). Bacillary load was higher in male and in patients aged 20–39 and 40–59 years compared to females and other age groups. From 2003 to 2013, there was a progressive reduction in annual NCDRs and an increase in the percentage of MB cases and of elderly patients in Brazil. These data suggest reduction of leprosy transmission in the country.Conclusion
Public health policies for leprosy control in endemic areas in Brazil should include activities especially addressed to men and to the elderly in order to further reduce M. leprae transmission.
Improving access to Chagas disease diagnosis and etiologic treatment in remote rural communities of the Argentine Chaco through strengthened primary health care and broad social participation
by Paula Sartor, Ivana Colaianni, M. Victoria Cardinal, Jacqueline Bua, Héctor Freilij, Ricardo E. GürtlerBackground
Rural populations in the Gran Chaco region have large prevalence rates of Trypanosoma cruzi infection and very limited access to diagnosis and treatment. We implemented an innovative strategy to bridge these gaps in 13 rural villages of Pampa del Indio held under sustained vector surveillance and control.Methodology
The non-randomized treatment program included participatory workshops, capacity strengthening of local health personnel, serodiagnosis, qualitative and quantitative PCRs, a 60-day treatment course with benznidazole and follow-up. Parents and healthcare agents were instructed on drug administration and early detection and notification of adverse drug-related reactions (ADR). Healthcare agents monitored medication adherence and ADRs at village level.Principal findings
The seroprevalence of T. cruzi infection was 24.1% among 395 residents up to 18 years of age examined. Serodiagnostic (70%) and treatment coverage (82%) largely exceeded local historical levels. Sixty-six (85%) of 78 eligible patients completed treatment with 97% medication adherence. ADRs occurred in 32% of patients, but most were mild and manageable. Four patients showing severe or moderate ADRs required treatment withdrawal. T. cruzi DNA was detected by qPCR in 47 (76%) patients before treatment, and persistently occurred in only one patient over 20–180 days posttreatment.Conclusions and significance
Our results demonstrate that diagnosis and treatment of T. cruzi infection in remote, impoverished rural areas can be effectively addressed through strengthened primary healthcare attention and broad social participation with adequate external support. This strategy secured high treatment coverage and adherence; effectively managed ADRs, and provided early evidence of positive therapeutic responses.
by Felipe Maurício Soeiro Sampaio, Bodo Wanke, Dayvison Francis Saraiva Freitas, Janice Mery Chicarino de Oliveira Coelho, Maria Clara Gutierrez Galhardo, Marcelo Rosandiski Lyra, Maria Cristina da Silva Lourenço, Rodrigo de Almeida Paes, Antonio Carlos Francesconi do ValleMycetoma is caused by the subcutaneous inoculation of filamentous fungi or aerobic filamentous bacteria that form grains in the tissue. The purpose of this study is to describe the epidemiologic, clinic, laboratory, and therapeutic characteristics of patients with mycetoma at the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil, between 1991 and 2014. Twenty-one cases of mycetoma were included in the study. There was a predominance of male patients (1.3:1) and the average patient age was 46 years. The majority of the cases were from the Southeast region of Brazil and the feet were the most affected anatomical region (80.95%). Eumycetoma prevailed over actinomycetoma (61.9% and 38.1% respectively). Eumycetoma patients had positive cultures in 8 of 13 cases, with isolation of Scedosporium apiospermum species complex (n = 3), Madurella mycetomatis (n = 2) and Acremonium spp. (n = 1). Two cases presented sterile mycelium and five were negative. Six of 8 actinomycetoma cases had cultures that were identified as Nocardia spp. (n = 3), Nocardia brasiliensis (n = 2), and Nocardia asteroides (n = 1). Imaging tests were performed on all but one patients, and bone destruction was identified in 9 cases (42.68%). All eumycetoma cases were treated with itraconazole monotherapy or combined with fluconazole, terbinafine, or amphotericin B. Actinomycetoma cases were treated with sulfamethoxazole plus trimethoprim or combined with cycles of amikacin sulphate. Surgical procedures were performed in 9 (69.2%) eumycetoma and in 3 (37.5%) actinomycetoma cases, with one amputation case in each group. Clinical cure occurred in 11 cases (7 for eumycetoma and 4 for actinomycetoma), and recurrence was documented in 4 of 21 cases. No deaths were recorded during the study. Despite of the scarcity of mycetoma in our institution the cases presented reflect the wide clinical spectrum and difficulties to take care of this neglected disease.
Holding back the tiger: Successful control program protects Australia from <i>Aedes albopictus</i> expansion
by Mutizwa Odwell Muzari, Gregor Devine, Joseph Davis, Bruce Crunkhorn, Andrew van den Hurk, Peter Whelan, Richard Russell, James Walker, Peter Horne, Gerhard Ehlers, Scott RitchieBackground
The Asian tiger mosquito, Aedes albopictus, is an important vector of dengue, chikungunya and Zika viruses and is a highly invasive and aggressive biter. Established populations of this species were first recognised in Australia in 2005 when they were discovered on islands in the Torres Strait, between mainland Australia and Papua New Guinea. A control program was implemented with the original goal of eliminating Ae. albopictus from the Torres Strait. We describe the evolution of management strategies that provide a template for Ae. albopictus control that can be adopted elsewhere.Methodology / Principal findings
The control strategy implemented between 2005 and 2008 targeted larval habitats using source reduction, insect-growth regulator and pyrethroid insecticide to control larvae and adults in the containers. However, the infrequency of insecticide reapplication, the continual accumulation and replacement of containers, and imminent re-introduction of mosquitoes through people’s movement from elsewhere compromised the program. Consequently, in 2009 the objective of the program changed from elimination to quarantine, with the goal of preventing Ae albopictus from infesting Thursday and Horn islands, which are the transport hubs connecting the Torres Strait to mainland Australia. However, larval control strategies did not prevent the species establishing on these islands in 2010. Thereafter, an additional strategy adopted by the quarantine program in early 2011 was harborage spraying, whereby the vegetated, well shaded resting sites of adult Ae. albopictus were treated with a residual pyrethroid insecticide. Inclusion of this additional measure led to a 97% decline in Ae. albopictus numbers within two years. In addition, the frequency of container treatment was increased to five weeks between treatments, compared to an average of 8 weeks that occurred in the earlier iterations of the program. By 2015 and 2016, Ae. albopictus populations on the two islands were undetectable in 70–90% of surveys conducted. Importantly, a comprehensive surveillance network in selected strategic areas has not identified established populations of this species on the Australian mainland.Conclusions / Significance
The program has successfully reduced Ae. albopictus populations on Thursday Island and Horn Island to levels where it is undetectable in up to 90% of surveys, and has largely removed the risk of mainland establishment via that route. The vector management strategies adopted in the later years of the program have been demonstrably successful and provide a practical management framework for dengue, chikungunya or Zika virus outbreaks vectored by Ae. albopictus. As of June 2016, Ae. albopictus had not established on the Australian mainland and this program has likely contributed significantly to this outcome.
Mosquito cell-derived West Nile virus replicon particles mimic arbovirus inoculum and have reduced spread in mice
by Brendan T. Boylan, Fernando R. Moreira, Tim W. Carlson, Kristen A. BernardHalf of the human population is at risk of infection by an arthropod-borne virus. Many of these arboviruses, such as West Nile, dengue, and Zika viruses, infect humans by way of a bite from an infected mosquito. This infectious inoculum is insect cell-derived giving the virus particles distinct qualities not present in secondary infectious virus particles produced by infected vertebrate host cells. The insect cell-derived particles differ in the glycosylation of virus structural proteins and the lipid content of the envelope, as well as their induction of cytokines. Thus, in order to accurately mimic the inoculum delivered by arthropods, arboviruses should be derived from arthropod cells. Previous studies have packaged replicon genome in mammalian cells to produce replicon particles, which undergo only one round of infection, but no studies exist packaging replicon particles in mosquito cells. Here we optimized the packaging of West Nile virus replicon genome in mosquito cells and produced replicon particles at high concentration, allowing us to mimic mosquito cell-derived viral inoculum. These particles were mature with similar genome equivalents-to-infectious units as full-length West Nile virus. We then compared the mosquito cell-derived particles to mammalian cell-derived particles in mice. Both replicon particles infected skin at the inoculation site and the draining lymph node by 3 hours post-inoculation. The mammalian cell-derived replicon particles spread from the site of inoculation to the spleen and contralateral lymph nodes significantly more than the particles derived from mosquito cells. This in vivo difference in spread of West Nile replicons in the inoculum demonstrates the importance of using arthropod cell-derived particles to model early events in arboviral infection and highlights the value of these novel arthropod cell-derived replicon particles for studying the earliest virus-host interactions for arboviruses.
by Pabitra Saha, Swagata Ganguly, Moytrey Chatterjee, Soumendu Bikash Das, Pratip K. Kundu, Subhasish K. Guha, Tamal K. Ghosh, Dilip K. Bera, Nandita Basu, Ardhendu K. MajiAsymptomatic leishmaniasis may drive the epidemic and an important challenge to reach the goal of joint Visceral Leishmaniasis (VL) elimination initiative taken by three Asian countries. The role of these asymptomatic carriers in disease transmission, prognosis at individual level and rate of transformation to symptomatic VL/Post Kala-azar Dermal Leishmaniasis (PKDL) needs to be evaluated. Asymptomatic cases were diagnosed by active mass survey in eight tribal villages by detecting antileishmanial antibody using rK39 based rapid diagnostic kits and followed up for three years to observe the pattern of sero-conversion and disease transformation. Out of 2890 total population, 2603 were screened. Antileishmanial antibody was detected in 185 individuals of them 96 had a history of VL/PKDL and 89 without such history. Seventy nine such individuals were classified as asymptomatic leishmaniasis and ten as active VL with a ratio of 7.9:1. Out of 79 asymptomatic cases 2 were lost to follow up as they moved to other places. Amongst asymptomatically infected persons, disease transformation in 8/77 (10.39%) and sero-conversion in 62/77 (80.52%) cases were noted. Seven (9.09%) remained sero-positive even after three years. Progression to clinical disease among asymptomatic individuals was taking place at any time up to three years after the baseline survey. If there are no VL /PKDL cases for two or more years, it does not mean that the area is free from leishmaniasis as symptomatic VL or PKDL may appear even after three years, if there are such asymptomatic cases. So, asymptomatic infected individuals need much attention for VL elimination programme that has been initiated by three adjoining endemic countries.
Podoconiosis, trachomatous trichiasis and cataract in northern Ethiopia: A comparative cross sectional study
by Helen Burn, Sintayehu Aweke, Tariku Wondie, Esmael Habtamu, Kebede Deribe, Saul Rajak, Stephen Bremner, Gail DaveyBackground
Rural populations in low-income countries commonly suffer from the co-morbidity of neglected tropical diseases (NTDs). Podoconiosis, trachomatous trichiasis (both NTDs) and cataract are common causes of morbidity among subsistence farmers in the highlands of northern Ethiopia. We explored whether podoconiosis was associated with cataract or trachomatous trichiasis (TT) among this population.Methods
A comparative cross-sectional study was conducted in East Gojam region, Amhara, Ethiopia in May 2016. Data were collected from patients previously identified as having podoconiosis and from matched healthy neighbourhood controls. Information on socio-demographic factors, clinical factors and past medical history were collected by an interview-administered questionnaire. Clinical examination involved grading of podoconiosis by examination of both legs, measurement of visual acuity, direct ophthalmoscopy of dilated pupils to grade cataract, and eyelid and corneal examination to grade trachoma. Multiple logistic regression was conducted to estimate independent association and correlates of podoconiosis, TT and cataract.Findings
A total of 700 participants were included in this study; 350 podoconiosis patients and 350 healthy neighbourhood controls. The prevalence of TT was higher among podoconiosis patients than controls (65 (18.6%) vs 43 (12.3%)) with an adjusted odds ratio OR 1.57 (95% CI 1.02–2.40), p = 0.04. There was no significant difference in prevalence of cataract between the two populations with an adjusted OR 0.83 (95% CI 0.55–1.25), p = 0.36. Mean best visual acuity was 0.59 (SD 0.06) in podoconiosis cases compared to 0.44 (SD 0.04) in controls, p<0.001. The proportion of patients classified as blind was higher in podoconiosis cases compared with healthy controls; 5.6% vs 2.0%; adjusted OR 2.63 (1.08–6.39), P = 0.03.Conclusions
Individuals with podoconiosis have a higher burden of TT and worse visual acuity than their matched healthy neighbourhood controls. Further research into the environmental and biological reasons for this co-morbidity is required. A shared approach to managing these two NTDs within the same population could be beneficial.