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Association of <i>Phlebotomus guggisbergi</i> with <i>L</i>. <i>major</i> and <i>L</i>. <i>tropica</i> in a complex transmission setting for cutaneous leishmaniasis in Gilgil, Nakuru county, Kenya

PLoS Neglected Tropical Diseases News - 18 October 2019 - 9:00pm

by Barrack O. Owino, Damaris Matoke-Muhia, Yasser Alraey, Jackline Milkah Mwangi, Johnstone M. Ingonga, Philip M. Ngumbi, Aitor Casas-Sanchez, Alvaro Acosta-Serrano, Daniel K. Masiga

Background

Phlebotomus (Larroussius) guggisbergi is among the confirmed vectors for cutaneous leishmaniasis (CL) transmission in Kenya. This scarring and stigmatizing form of leishmaniasis accounts for over one million annual cases worldwide. Most recent CL epidemics in Kenya have been reported in Gilgil, Nakuru County, where the disease has become a public health issue. However, little is known about the factors that drive its transmission. Here, we sought to determine the occurrence, distribution and host blood feeding preference of the vectors, and to identify Leishmania species and infection rates in sandflies using molecular techniques. This information could lead to a better understanding of the disease transmission and improvement of control strategies in the area.

Methodology/ Principal findings

An entomological survey of sandflies using CDC light traps was conducted for one week per month in April 2016, and in June and July 2017 from five villages of Gilgil, Nakuru county; Jaica, Sogonoi, Utut, Gitare and Njeru. Sandflies were identified to species level using morphological keys and further verified by PCR analysis of cytochrome c oxidase subunit I (COI) gene. Midguts of female sandflies found to harbour Leishmania were ruptured and the isolated parasites cultured in Novy-MacNeal-Nicolle (NNN) media overlaid with Schneider’s insect media to identify the species. Leishmania parasite screening and identification in 198 randomly selected Phlebotomus females and parasite cultures was done by PCR-RFLP analysis of ITS1 gene, nested kDNA-PCR and real-time PCR-HRM followed by sequencing. Bloodmeal source identification was done by real-time PCR-HRM of the vertebrate cytochrome-b gene. A total of 729 sandflies (males: n = 310; females: n = 419) were collected from Utut (36.6%), Jaica (24.3%), Sogonoi (34.4%), Njeru (4.5%), and Gitare (0.1%). These were found to consist of nine species: three Phlebotomus spp. and six Sergentomyia spp. Ph. guggisbergi was the most abundant species (75.4%, n = 550) followed by Ph. saevus sensu lato (11.3%, n = 82). Sandfly species distribution across the villages was found to be significantly different (p<0.001) with Jaica recording the highest diversity. The overall Leishmania infection rate in sandflies was estimated at 7.07% (14/198). Infection rates in Ph. guggisbergi and Ph. saevus s.l. were 9.09% (12/132) and 3.57% (2/56) respectively. L. tropica was found to be the predominant parasite in Gilgil with an overall infection rate of 6.91% (13/188) in Ph. guggisbergi (n = 11) and Ph. saevus s.l. (n = 2) sandflies. However, PCR analysis also revealed L. major infection in one Ph. guggisbergi specimen. Bloodmeal analysis in the 74 blood-fed sandflies disclosed a diverse range of vertebrate hosts in Ph. guggisbergi bloodmeals, while Ph. saevus s.l. fed mainly on humans.

Conclusions/ Significance

The high infection rates of L. tropica and abundance of Ph. guggisbergi in this study confirms this sandfly as a vector of L. tropica in Kenya. Furthermore, isolation of live L. tropica parasites from Ph. saevus s.l. suggest that there are at least three potential vectors of this parasite species in Gilgil; Ph. guggisbergi, Ph. aculeatus and Ph. saevus s.l. Molecular identification of L. major infections in Ph. guggisbergi suggested this sandfly species as a potential permissive vector of L. major, which needs to be investigated further. Sandfly host preference analysis revealed the possibility of zoonotic transmissions of L. tropica in Gilgil since the main vector (Ph. guggisbergi) does not feed exclusively on humans but also other vertebrate species. Further investigations are needed to determine the potential role of these vertebrate species in L. tropica and L. major transmission in the area.

Genetic and phenotypic characterization of recently discovered enterovirus D type 111

PLoS Neglected Tropical Diseases News - 17 October 2019 - 9:00pm

by Serge Alain Sadeuh-Mba, Marie-Line Joffret, Arthur Mazitchi, Marie-Claire Endegue-Zanga, Richard Njouom, Francis Delpeyroux, Ionela Gouandjika-Vasilache, Maël Bessaud

Members of the species Enterovirus D (EV-D) remain poorly studied. The two first EV-D types (EV-D68 and EV-D70) have regularly caused outbreaks in humans since their discovery five decades ago but have been neglected until the recent occurrence of severe respiratory diseases due to EV-D68. The three other known EV-D types (EV-D94, EV-D111 and EV-D120) were discovered in the 2000s-2010s in Africa and have never been observed elsewhere. One strain of EV-D111 and all known EV-D120s were detected in stool samples of wild non-human primates, suggesting that these viruses could be zoonotic viruses. To date, EV-D111s are only known through partial genetic sequences of the few strains that have been identified so far. In an attempt to bring new pieces to the puzzle, we genetically characterized four EV-D111 strains (among the seven that have been reported until now). We observed that the EV-D111 strains from human samples and the unique simian EV-D111 strain were not phylogenetically distinct, thus suggesting a recent zoonotic transmission. We also discovered evidences of probable intertypic genetic recombination events between EV-D111s and EV-D94s. As recombination can only happen in co-infected cells, this suggests that EV-D94s and EV-D111s share common replication sites in the infected hosts. These sites could be located in the gut since the phenotypic analysis we performed showed that, contrary to EV-D68s and like EV-D94s, EV-D111s are resistant to acid pHs. We also found that EV-D111s induce strong cytopathic effects on L20B cells, a cell line routinely used to specifically detect polioviruses. An active circulation of EV-D111s among humans could then induce a high number of false-positive detection of polioviruses, which could be particularly problematic in Central Africa, where EV-D111 circulates and which is a key region for poliovirus eradication.

Access to prompt diagnosis: The missing link in preventing mental health disorders associated with neglected tropical diseases

PLoS Neglected Tropical Diseases News - 17 October 2019 - 9:00pm

by Albert Picado, Sarah Nogaro, Israel Cruz, Sylvain Biéler, Laura Ruckstuhl, Jon Bastow, Joseph Mathu Ndung’u

Positive association between <i>Brucella</i> spp seroprevalences in livestock and humans from a cross-sectional study in Garissa and Tana River Counties, Kenya

PLoS Neglected Tropical Diseases News - 17 October 2019 - 9:00pm

by Salome Kairu-Wanyoike, Doris Nyamwaya, Martin Wainaina, Johanna Lindahl, Enoch Ontiri, Salome Bukachi, Ian Njeru, Joan Karanja, Rosemary Sang, Delia Grace, Bernard Bett

Background

Brucella spp. is a zoonotic bacterial agent of high public health and socio-economic importance. It infects many species of animals including wildlife, and people may get exposed through direct contact with an infected animal or consumption of raw or undercooked animal products. A linked livestock-human cross-sectional study to determine seroprevalences and risk factors of brucellosis in livestock and humans was designed. Estimates were made for intra-cluster correlation coefficients (ICCs) for these observations at the household and village levels.

Methodology

The study was implemented in Garissa (specifically Ijara and Sangailu areas) and Tana River (Bura and Hola) counties. A household was the unit of analysis and the sample size was derived using the standard procedures. Serum samples were obtained from selected livestock and people from randomly selected households. Humans were sampled in both counties, while livestock could be sampled only in Tana River County. Samples obtained were screened for anti-Brucella IgG antibodies using ELISA kits. Data were analyzed using generalized linear mixed effects logistic regression models with the household (herd) and village being used as random effects.

Results

The overall Brucella spp. seroprevalences were 3.47% (95% confidence interval [CI]: 2.72–4.36%) and 35.81% (95% CI: 32.87–38.84) in livestock and humans, respectively. In livestock, older animals and those sampled in Hola had significantly higher seroprevalences than younger ones or those sampled in Bura. Herd and village random effects were significant and ICC estimates associated with these variables were 0.40 (95% CI: 0.22–0.60) and 0.24 (95% CI: 0.08–0.52), respectively. In humans, Brucella spp. seroprevalence was significantly higher in older people, males, and people who lived in pastoral areas than younger ones, females or those who lived in irrigated or riverine areas. People from households that had at least one seropositive animal were 3.35 (95% CI: 1.51–7.41) times more likely to be seropositive compared to those that did not. Human exposures significantly clustered at the household level; the ICC estimate obtained was 0.21 (95% CI: 0.06–0.52).

Conclusion

The presence of a Brucella spp.-seropositive animal in a household significantly increased the odds of Brucella spp. seropositivity in humans in that household. Exposure to Brucella spp. of both livestock and humans clustered significantly at the household level. This suggests that risk-based surveillance measures, guided by locations of primary cases reported, either in humans or livestock, can be used to detect Brucella spp. infections in livestock or humans, respectively.

Analysis in a murine model points to IgG responses against the 34k2 salivary proteins from <i>Aedes albopictus</i> and <i>Aedes aegypti</i> as novel promising candidate markers of host exposure to <i>Aedes</i> mosquitoes

PLoS Neglected Tropical Diseases News - 16 October 2019 - 9:00pm

by Sara Buezo Montero, Paolo Gabrieli, Francesco Severini, Leonardo Picci, Marco Di Luca, Federico Forneris, Luca Facchinelli, Marta Ponzi, Fabrizio Lombardo, Bruno Arcà

Background

Aedes mosquitoes are vectors of arboviral diseases of great relevance for public health. The recent outbreaks of dengue, Zika, chikungunya and the rapid worldwide spreading of Aedes albopictus emphasize the need for improvement of vector surveillance and control. Host antibody response to mosquito salivary antigens is emerging as a relevant additional tool to directly assess vector-host contact, monitor efficacy of control interventions and evaluate risk of arboviral transmission.

Methodology/principal findings

Groups of four BALB/c mice were immunized by exposure to bites of either Aedes albopictus or Aedes aegypti. The 34k2 salivary proteins from Ae. albopictus (al34k2) and Ae. aegypti (ae34k2) were expressed in recombinant form and Ae. albopictus salivary peptides were designed through B-cell epitopes prediction software. IgG responses to salivary gland extracts, peptides, al34k2 and ae34k2 were measured in exposed mice. Both al34k2 and ae34k2, with some individual and antigen-specific variation, elicited a clearly detectable antibody response in immunized mice. Remarkably, the two orthologous proteins showed very low level of immune cross-reactivity, suggesting they may eventually be developed as species-specific markers of host exposure. The al34k2 immunogenicity and the limited immune cross-reactivity to ae34k2 were confirmed in a single human donor hyperimmune to Ae. albopictus saliva.

Conclusions/significance

Our study shows that exposure to bites of Ae. albopictus or Ae. aegypti evokes in mice species-specific IgG responses to al34k2 or ae34k2, respectively. Deeper understanding of duration of antibody response and validation in natural conditions of human exposure to Aedes mosquitoes are certainly needed. However, our findings point to the al34k2 salivary protein as a promising potential candidate for the development of immunoassays to evaluate human exposure to Ae. albopictus. This would be a step forward in the establishment of a serological toolbox for the simultaneous assessment of human exposure to Aedes vectors and the pathogens they transmit.

A systematic review of the epidemiology of human monkeypox outbreaks and implications for outbreak strategy

PLoS Neglected Tropical Diseases News - 16 October 2019 - 9:00pm

by Ellen N. Beer, V. Bhargavi Rao

Monkeypox is a vesicular-pustular illness that carries a secondary attack rate in the order of 10% in contacts unvaccinated against smallpox. Case fatality rates range from 1 to 11%, but scarring and other sequelae are common in survivors. It continues to cause outbreaks in remote populations in Central and West Africa, in areas with poor access and weakened or disrupted surveillance capacity and information networks. Recent outbreaks in Nigeria (2017-18) and Cameroon (2018) have occurred where monkeypox has not been reported for over 20 years. This has prompted concerns over whether there have been changes in the biology and epidemiology of the disease that may in turn have implications for how outbreaks and cases should best be managed. A systematic review was carried out to examine reported data on human monkeypox outbreaks over time, and to identify if and how epidemiology has changed. Published and grey literature were critically analysed, and data extracted to inform recommendations on outbreak response, use of case definitions and public health advice. The level of detail, validity of data, geographical coverage and consistency of reporting varied considerably across the 71 monkeypox outbreak documents obtained. An increase in cases reported over time was supported by literature from the Democratic Republic of Congo (DRC). Data were insufficient to measure trends in secondary attack rates and case fatality rates. Phylogenetic analyses consistently identify two strains of the virus without evidence of emergence of a new strain. Understanding of monkeypox virulence with regard to clinical presentation by strain is minimal, with infrequent sample collection and laboratory analysis. A variety of clinical and surveillance case definitions are described in the literature: two definitions have been formally evaluated and showed high sensitivity but low specificity. These were specific to a Congo-Basin (CB) strain–affected area of the DRC where they were used. Evidence on use of antibiotics for prophylaxis against secondary cutaneous infection is anecdotal and limited. Current evidence suggests there has been an increase in total monkeypox cases reported by year in the DRC irrespective of advancements in the national Integrated Disease Surveillance and Response (IDSR) system. There has been a marked increase in number of individual monkeypox outbreak reports, from outside the DRC in between 2010 and 2018, particularly in the Central African Republic (CAR) although this does not necessarily indicate an increase in annual cases over time in these areas. The geographical pattern reported in the Nigeria outbreak suggests a possible new and widespread zoonotic reservoir requiring further investigation and research. With regards to outbreak response, increased attention is warranted for high-risk patient groups, and nosocomial transmission risks. The animal reservoir remains unknown and there is a dearth of literature informing case management and successful outbreak response strategies. Up-to-date complete, consistent and longer-term research is sorely needed to inform and guide evidence-based response and management of monkeypox outbreaks.

Kaposi’s sarcoma-associated herpesvirus seropositivity is associated with parasite infections in Ugandan fishing communities on Lake Victoria islands

PLoS Neglected Tropical Diseases News - 16 October 2019 - 9:00pm

by Angela Nalwoga, Emily L. Webb, Belinda Chihota, Wendell Miley, Bridgious Walusimbi, Jacent Nassuuna, Richard E. Sanya, Gyaviira Nkurunungi, Nazzarena Labo, Alison M. Elliott, Stephen Cose, Denise Whitby, Robert Newton

We investigated the impact of helminths and malaria infection on Kaposi’s sarcoma associated herpesvirus (KSHV) seropositivity, using samples and data collected from a cluster-randomised trial of intensive versus standard anthelminthic treatment. The trial was carried out in 2012 to 2016 among fishing communities on Lake Victoria islands in Uganda. Plasma samples from 2881 participants from two household surveys, the baseline (1310 participants) and the final (1571 participants) surveys were tested for KSHV IgG antibody responses to K8.1 and ORF73 recombinant proteins using ELISA. The baseline survey was carried out before the trial intervention while the final survey was carried out after three years of the trial intervention. Additionally, a subset sample of 372 participants from the final survey was tested for IgE, IgG and IgG4 antibody concentrations to S. mansoni adults worm antigen (SWA) and S. mansoni egg antigen (SEA) using ELISA. Infection by helminths (S. mansoni, N. americanus, T. trichiura and S. stercoralis) was diagnosed using real-time PCR, urine circulating cathodic antigen (CCA) and stool microscopy (Kato-Katz method) while malaria infection was diagnosed using microscopy. We analysed the relationship between helminth and malaria infections and KSHV seropositivity using regression modelling, allowing for survey design. At baseline, 56% of the participants were male while 48% of the participants were male in the final survey. The most prevalent helminth infection was S. mansoni (at baseline 52% and 34% in the final survey by microscopy, 86% by CCA and 50% by PCR in the final survey). KSHV seropositivity was 66% (baseline) and 56% (final survey) among those 1–12 years and >80% in those 13+ years in both surveys; malaria parasitaemia prevalence was 7% (baseline) and 4% (final survey). At baseline, individuals infected with S. mansoni (detected by microscopy) were more likely to be KSHV seropositive (aOR = 1.86 (1.16, 2.99) p = 0.012) and had higher anti-K8.1 antibody levels (acoefficient = 0.03 (0.01, 0.06) p = 0.02). In the final survey, S. mansoni (by microscopy, adjusted Odds Ratio (aOR = 1.43 (1.04–1.95), p = 0.028) and malaria parasitaemia (aOR = 3.49 (1.08–11.28), p = 0.038) were positively associated with KSHV seropositivity. Additionally, KSHV seropositive participants had higher S. mansoni-specific IgE and IgG antibody concentrations in plasma. Furthermore, HIV infected individuals on cART were less likely to be KSHV seropositive compared to HIV negative individuals (aOR = 0.46 (0.30, 0.71) p = 0.002). Schistosoma species skew the immune response towards Th2 and regulatory responses, which could impact on KSHV reactivation if co-infected with both organisms.

Human <i>Chrysomya bezziana</i> myiasis: A systematic review

PLoS Neglected Tropical Diseases News - 16 October 2019 - 9:00pm

by Xianyi Zhou, Dzinkambani Moffat Kambalame, Sitong Zhou, Xiang Guo, Dan Xia, Yemei Yang, Rangke Wu, Juan Luo, Fenglong Jia, Mingchi Yuen, Yuehua Xu, Geyang Dai, Li Li, Tian Xie, Santhosh Puthiyakunnon, Wenxia Wei, Lixian Xie, Siting Liang, Yuqin Feng, Songgen Huang, Yongxuan Hu, Qianzhen Mo, Rongjia Mai, Xiaoqing Zhang, Philip Spradbery, Xiaohong Zhou

Background

Myiasis due to Old World screw-worm fly, Chrysomya bezziana, is an important obligate zoonotic disease in the OIE-list of diseases and is found throughout much of Africa, the Indian subcontinent, southeast and east Asia. C. bezziana myiasis causes not only morbidity and death to animals and humans, but also economic losses in the livestock industries. Because of the aggressive and destructive nature of this disease in hosts, we initiated this study to provide a comprehensive understanding of human myiasis caused by C. bezziana.

Methods

We searched the databases in English (PubMed, Embase and African Index Medicus) and Chinese (CNKI, Wanfang, and Duxiu), and international government online reports to 6th February, 2019, to identify studies concerning C. bezziana. Another ten human cases in China and Papua New Guinea that our team had recorded were also included.

Results

We retrieved 1,048 reports from which 202 studies were ultimately eligible for inclusion in the present descriptive analyses. Since the first human case due to C. bezziana was reported in 1909, we have summarized 291 cases and found that these cases often occurred in patients with poor hygiene, low socio-economic conditions, old age, and underlying diseases including infections, age-related diseases, and noninfectious chronic diseases. But C. bezziana myiasis appears largely neglected as a serious medical or veterinary condition, with human and animal cases only reported in 16 and 24 countries respectively, despite this fly species being recorded in 44 countries worldwide.

Conclusion

Our findings indicate that cryptic myiasis cases due to the obligate parasite, C. bezziana, are under-recognized. Through this study on C. bezziana etiology, clinical features, diagnosis, treatment, epidemiology, prevention and control, we call for more vigilance and awareness of the disease from governments, health authorities, clinicians, veterinary workers, nursing homes, and also the general public.

Acute <i>Toxoplasma</i> infection in pregnant women worldwide: A systematic review and meta-analysis

PLoS Neglected Tropical Diseases News - 14 October 2019 - 9:00pm

by Ali Rostami, Seyed Mohammad Riahi, Despina G. Contopoulos-Ioannidis, H. Ray Gamble, Yadollah Fakhri, Malihe Nourollahpour Shiadeh, Masoud Foroutan, Hamed Behniafar, Ali Taghipour, Yvonne A. Maldonado, Ali H. Mokdad, Robin B. Gasser

Background

Acute Toxoplasma infection (ATI) during pregnancy, if left untreated, can cause severe adverse outcomes for the fetus and newborn. Here, we undertook a meta-analysis to estimate the worldwide prevalence of ATI in pregnant women.

Methods

We searched international databases for studies published between January 1988 and November 2018. We included population-based cross-sectional and prospective cohort studies that reported the prevalence of ATI in pregnant women. Data were synthesized using a random effect model to calculate the overall prevalence of ATI (with a 95% CI) in six WHO regions and globally. We also performed linear meta-regression analyses to investigate associations of maternal, socio-demographic, geographical and climate parameters with the prevalence of ATI.

Results

In total, 217 studies comprising 902,228 pregnant women across 74 countries were included in the meta-analysis. The overall prevalence of ATI in pregnant women globally was 1.1% (95% CI: 0.9–1.2%). In studies where more strict criteria for ATI were used, the overall prevalence was 0.6% (95% CI: 0.4–0.7%). The prevalence was highest in the Eastern Mediterranean region (2.5%; 95%CI: 1.7–3.4%) and lowest in the European region (0.5%; 95% CI: 0.4–0.7%). A significantly higher prevalence of ATI was found in countries with lower income levels (P = 0.027), lower human development indices (P = 0.04), higher temperatures (P = 0.02) and lower latitudes (P = 0.005) and longitudes (P = 0.02).

Conclusions

The risk of acquiring ATI during gestation is clinically important and preventive measures to avoid exposure of pregnant women to Toxoplasma infection should be strictly applied.

High burden and seasonal variation of paediatric scabies and pyoderma prevalence in The Gambia: A cross-sectional study

PLoS Neglected Tropical Diseases News - 14 October 2019 - 9:00pm

by Edwin P. Armitage, Elina Senghore, Saffiatou Darboe, Momodou Barry, Janko Camara, Sulayman Bah, Michael Marks, Carla Cerami, Anna Roca, Martin Antonio, Claire E. Turner, Thushan I. de Silva

Background

Scabies is a WHO neglected tropical disease common in children in low- and middle-income countries. Excoriation of scabies lesions can lead to secondary pyoderma infection, most commonly by Staphyloccocus aureus and Streptococcus pyogenes (group A streptococcus, GAS), with the latter linked to acute post-streptococcal glomerulonephritis (APSGN) and potentially rheumatic heart disease (RHD). There is a paucity of data on the prevalence of these skin infections and their bacterial aetiology from Africa.

Methodology/Principal findings

A cross-sectional study, conducted over a four-month period that included the dry and rainy season, was conducted to determine the prevalence of common skin infections in Sukuta, a peri-urban settlement in western Gambia, in children <5 years. Swabs from pyoderma lesions were cultured for S. aureus and GAS. Of 1441 children examined, 15.9% had scabies (95% CI 12.2–20.4), 17.4% had pyoderma (95% CI 10.4–27.7) and 9.7% had fungal infections (95% CI 6.6–14.0). Scabies were significantly associated with pyoderma (aOR 2.74, 95% CI 1.61–4.67). Of 250 pyoderma swabs, 80.8% were culture-positive for S. aureus, and 50.8% for GAS. Participants examined after the first rains were significantly more likely to have pyoderma than those examined before (aRR 2.42, 95% CI 1.38–4.23), whereas no difference in scabies prevalence was seen (aRR 1.08, 95% CI 0.70–1.67). Swab positivity was not affected by the season.

Conclusions/Significance

High prevalence of scabies and pyoderma were observed. Pyoderma increased significantly during rainy season. Given the high prevalence of GAS pyoderma among children, further research on the association with RHD in West Africa is warranted.

Supporting evidence for a human reservoir of invasive non-Typhoidal <i>Salmonella</i> from household samples in Burkina Faso

PLoS Neglected Tropical Diseases News - 14 October 2019 - 9:00pm

by Annelies S. Post, Seydou Nakanabo Diallo, Issa Guiraud, Palpouguini Lompo, Marc Christian Tahita, Jessica Maltha, Sandra Van Puyvelde, Wesley Mattheus, Benedikt Ley, Kamala Thriemer, Eli Rouamba, Karim Derra, Stijn Deborggraeve, Halidou Tinto, Jan Jacobs

Background

Salmonella Typhimurium and Enteritidis are major causes of bloodstream infection in children in sub-Saharan Africa. This study assessed evidence for their zoonotic versus human reservoir.

Methods

Index patients were children with blood culture confirmed Salmonella infection recruited during a microbiological surveillance study in Nanoro, rural Burkina between May 2013 and August 2014. After consent, their households were visited. Stool from household members and livestock (pooled samples per species) as well as drinking water were cultured for Salmonella. Isolates with identical serotype obtained from index patient and any household sample were defined as “paired isolates” and assessed for genetic relatedness by multilocus variable number tandem-repeat analysis (MLVA) and whole-genome sequencing (WGS).

Results

Twenty-nine households were visited for 32/42 (76.2%) eligible index patients: two households comprised two index patients each, and in a third household the index patient had a recurrent infection. Among the 32 index patients, serotypes were Salmonella Typhimurium (n = 26), Salmonella Enteritidis (n = 5) and Salmonella Freetown (n = 1). All Typhimurium isolates were sequence type (ST)313. Median delay between blood culture sampling and household visits was 13 days (range 6–26). Salmonella was obtained from 16/186 (8.6%) livestock samples (13 serotypes) and 18/290 (6.2%) household members (9 serotypes). None of the water samples yielded Salmonella. Paired Salmonella Typhimurium isolates were obtained from three households representing four index patients. MLVA types were identical in two pairs and similar in the third (consisting of two index patients and one household member). WGS showed a strong genetic relatedness with 0 to 2 core genome SNPs difference between pairs on a household level. Livestock samples did not yield any Salmonella Typhimurium or Salmonella Enteritidis, and the latter was exclusively obtained from blood culture. Other serotypes shared by human and/or livestock carriers in the same household were Salmonella Derby, Drac, Tennessee and Muenster.

Conclusions/Significance

The current study provides further evidence of a human reservoir for invasive non-Typhoidal Salmonella (iNTS) in sub-Saharan Africa.

Differential impact of mass and targeted praziquantel delivery on schistosomiasis control in school-aged children: A systematic review and meta-analysis

PLoS Neglected Tropical Diseases News - 11 October 2019 - 9:00pm

by Danielle M. Cribb, Naomi E. Clarke, Suhail A. R. Doi, Susana Vaz Nery

Background

Schistosomiasis is a widespread public health concern in the poorest regions of the world. The principal control strategy is regular praziquantel administration to school-aged children in endemic areas. With calls for the elimination of schistosomiasis as a public health problem, expanding praziquantel delivery to all community members has been advocated. This systematic review and meta-analysis compares the impact of community-wide and child-targeted praziquantel distribution on schistosomiasis prevalence and intensity in school-aged children.

Methodology/Principal findings

We searched MEDLINE, Embase and Web of Science to identify papers that reported schistosome prevalence before and after praziquantel administration, either to children only or to all community members. Extracted data included Schistosoma species, drug administration strategy, number of treatment rounds, follow-up interval and prevalence and intensity before and after treatment. We used inverse variance weighted generalised linear models to examine the impact of mass versus targeted drug administration on prevalence reduction, and weighted boxplots to examine the impact on infection intensity reduction. This study is registered with PROSPERO, number CRD42018095377.In total, 34 articles were eligible for systematic review and 28 for meta-analysis. Schistosoma mansoni was reported in 20 studies; Schistosoma haematobium in 19 studies, and Schistosoma japonicum in two studies. Results of generalised linear models showed no detectable difference between mass and targeted treatment strategies on prevalence reduction in school-aged children for S. mansoni (odds ratio 0.47, 95%CI 0.13–1.68, p = 0.227) and S. haematobium (0.41, 95%CI 0.06–3.03, p = 0.358). Box plots also showed no apparent differences in intensity reduction between the two treatment strategies.

Conclusions/Significance

The results of this meta-analysis do not support the hypothesis that community-wide treatment is more effective than targeted treatment at reducing schistosomiasis infections in children. This may be due to the relatively small number of included studies, insufficient treatment coverage, persistent infection hotspots and unmeasured confounders. Further field-based studies comparing mass and targeted treatment are required.

Molluscicidal activity and physiological toxicity of quaternary benzo[c]phenanthridine alkaloids (QBAs) from <i>Macleaya cordata</i> fruits on <i>Oncomelania hupensis</i>

PLoS Neglected Tropical Diseases News - 11 October 2019 - 9:00pm

by Wenshan Ke, Chang Tu, Dezhi Cao, Xiong Lin, Qiqiang Sun, Qian Zhang

Schistosomiasis is a serious worldwide parasitic disease. One of the best ways to control schistosomiasis is to control the population of Oncomelania hupensis snails. We sought to identify a high-efficiency biogenic molluscicide against Oncomelania with low toxicity, to avoid chemical molluscicide contamination and toxicity in aquatic organisms. We extracted quaternary benzo[c]phenanthridine alkaloids (QBAs) from Macleaya cordata fruits. Molluscicidal activity of the QBAs against Oncomelania was determined using bioassay. Our results showed that the extracted QBAs had a strong molluscicidal effect. In treatment of O. hupensis with QBAs for 48 h and 72 h, the lethal concentration (LC50) was 2.89 mg/L and 1.29 mg/L, respectively. The molluscicidal activity of QBAs was close to that of niclosamide (ethanolamine salt), indicating that QBAs have potential development value as novel biogenic molluscicides. We also analyzed physiological toxicity mechanisms by examining the activity of several important detoxification enzymes. We measured the effect of the extracted QBAs on the activities of glutathione S-transferase (GST), carboxylesterase (CarE), acid phosphatase (ACP), and alkaline phosphatase (AKP) in the liver of O. hupensis. We found that the effects of QBAs on detoxification metabolism in O. hupensis were time and concentration dependent. The activities of GST, CarE, AKP, and ACP in the liver of snails increased significantly in the early stage of treatment (24 h), but decreased sharply in later stages (120 h), compared with these activities in controls. GST, CarE, AKP, and ACP activity in the liver of snails treated with LC50 QBAs for 120 h decreased by 62.3%, 78.1%, 59.2%, and 68.6%, respectively. Our results indicate that these enzymes were seriously inhibited by the extracted QBAs and the detoxification and metabolic functions of the liver gradually weakened, leading to poisoning, which could be the main cause of death in O. hupensis snails.

Trends of leprosy and multibacillary infection in the state of Georgia since the early 1900s

PLoS Neglected Tropical Diseases News - 11 October 2019 - 9:00pm

by Carter D. McCormick, Jacqueline Lea, Barbara M. Stryjewska, Ashton Thompson, Jessica K. Fairley

Few investigations to date have analyzed the epidemiology of Hansen’s disease (leprosy) in the United States, and in particular, if birth location is related to multibacillary versus paucibacillary leprosy. We collected data on 123 patients diagnosed with leprosy in Georgia from the National Hansen’s Disease Program from 1923—January 2018. A logistic regression model was built to examine the relationship between country of origin (U.S.-born or immigrant) and the type of leprosy. While the model showed no significant relationship between country of origin and type of leprosy, being Asian or Pacific Islander was associated with a higher odds of multibacillary disease (aOR = 5.71; 95% CI: 1.25–26.29). Furthermore, since the early 1900s, we found an increasing trend of leprosy reports in Georgia among both domestic born and immigrant residents, despite the overall decrease in cases in the United States during the same time period. More research is therefore necessary to further evaluate risk for multibacillary leprosy in certain populations and to create targeted interventions and prevention strategies.

Enduring extreme climate: Effects of severe drought on <i>Triatoma brasiliensis</i> populations in wild and man-made habitats of the Caatinga

PLoS Neglected Tropical Diseases News - 10 October 2019 - 9:00pm

by Antonia C. Ribeiro, Otília Sarquis, Marli M. Lima, Fernando Abad-Franch

Background

Triatoma brasiliensis, a triatomine-bug vector of Chagas disease, evolved in the semiarid Caatinga, where it occupies rocky outcrops, shrubby cacti, and human dwellings. Dwellings and rocks are considered high-quality microhabitats for this saxicolous species, whereas cacti probably represent secondary, lower-quality microhabitats. This ‘microhabitat-quality hierarchy’ hypothesis predicts that T. brasiliensis populations occupying dwellings or rocks should endure harsh environmental conditions better than their cactus-living relatives.

Methods/Findings

We tested this prediction by comparing T. brasiliensis infestation (proportion of microhabitats with bugs), density (bugs per microhabitat), and crowding (bugs per infested microhabitat) in dwellings, rocks, and cacti sampled before and during the extreme drought that ravaged the Caatinga in 2012–2016. We used random-intercepts generalized linear mixed models to account for microhabitat spatial clustering and for variations in bug-catch effort; we assessed model performance and computed model-averaged effect estimates using Akaike’s information criterion. Pre-drought infestation was similar across microhabitat types; during the drought, infestation remained stable in dwellings and rocks but dropped in cacti. Pre-drought bug density declined from dwellings to rocks to cacti; an additional decline associated with the drought was largely comparable across microhabitats, albeit perhaps somewhat larger in cacti. Finally, pre-drought bug crowding was higher in dwellings than in rocks or cacti and changed little during the drought–possibly with a downward trend in dwellings and an upward trend in cacti.

Conclusions

Triatoma brasiliensis populations fared better in dwellings and rocks than in cacti during extreme drought. Estimates of microhabitat and drought effects on infestation, density, and crowding suggest that only a few cacti (versus many rocks and dwellings) represent good-quality habitat under such extremely harsh conditions. Our findings provide empirical support to the microhabitat-quality hierarchy hypothesis, and imply that T. brasiliensis can endure extreme climate by exploiting high-quality microhabitats, whether wild or man-made, in the semiarid Caatinga.

Identification of a systemic interferon-γ inducible antimicrobial gene signature in leprosy patients undergoing reversal reaction

PLoS Neglected Tropical Diseases News - 10 October 2019 - 9:00pm

by Rosane M. B. Teles, Jing Lu, Maria Tió-Coma, Isabela M. B. Goulart, Sayera Banu, Deanna Hagge, Kidist Bobosha, Tom Ottenhoff, Matteo Pellegrini, Annemieke Geluk, Robert L. Modlin

Reversal reactions (RRs) in leprosy are characterized by a reduction in the number of bacilli in lesions associated with an increase in cell-mediated immunity against the intracellular bacterium Mycobacterium leprae, the causative pathogen of leprosy. To identify the mechanisms that contribute to cell-mediated immunity in leprosy, we measured changes in the whole blood-derived transcriptome of patients with leprosy before, during and after RR. We identified an ‘RR signature’ of 1017 genes that were upregulated at the time of the clinical diagnosis of RR. Using weighted gene correlated network analysis (WGCNA), we detected a module of 794 genes, bisque4, that was significantly correlated with RR, of which 434 genes were part of the RR signature. An enrichment for both IFN-γ and IFN-β downstream gene pathways was present in the RR signature as well as the RR upregulated genes in the bisque4 module, including those encoding proteins of the guanylate binding protein (GBP) family that contributes to antimicrobial responses against mycobacteria. Specifically, GBP1, GBP2, GBP3 and GBP5 mRNAs were upregulated in the RR peripheral blood transcriptome, with GBP1, GBP2 and GBP5 mRNAs also upregulated in the RR disease lesion transcriptome. These data indicate that RRs involve a systemic upregulation of IFN-γ downstream genes including GBP family members as part of the host antimicrobial response against mycobacteria.

Management of insecticide resistance in the major Aedes vectors of arboviruses: Advances and challenges

PLoS Neglected Tropical Diseases News - 10 October 2019 - 9:00pm

by Isabelle Dusfour, John Vontas, Jean-Philippe David, David Weetman, Dina M. Fonseca, Vincent Corbel, Kamaraju Raghavendra, Mamadou B. Coulibaly, Ademir J. Martins, Shinji Kasai, Fabrice Chandre

Background

The landscape of mosquito-borne disease risk has changed dramatically in recent decades, due to the emergence and reemergence of urban transmission cycles driven by invasive Aedes aegypti and Ae. albopictus. Insecticide resistance is already widespread in the yellow fever mosquito, Ae. Aegypti; is emerging in the Asian tiger mosquito Ae. Albopictus; and is now threatening the global fight against human arboviral diseases such as dengue, yellow fever, chikungunya, and Zika. Because the panel of insecticides available for public health is limited, it is of primary importance to preserve the efficacy of existing and upcoming active ingredients. Timely implementation of insecticide resistance management (IRM) is crucial to maintain the arsenal of effective public health insecticides and sustain arbovirus vector control.

Methodology and principal findings

This Review is one of a series being generated by the Worldwide Insecticide resistance Network (WIN) and aims at defining the principles and concepts underlying IRM, identifying the main factors affecting the evolution of resistance, and evaluating the value of existing tools for resistance monitoring. Based on the lessons taken from resistance strategies used for other vector species and agricultural pests, we propose a framework for the implementation of IRM strategies for Aedes mosquito vectors.

Conclusions and significance

Although IRM should be a fixture of all vector control programs, it is currently often absent from the strategic plans to control mosquito-borne diseases, especially arboviruses. Experiences from other public health disease vectors and agricultural pests underscore the need for urgent action in implementing IRM for invasive Aedes mosquitoes. Based on a plan developed for malaria vectors, here we propose some key activities to establish a global plan for IRM in Aedes spp.

Selecting behaviour change priorities for trachoma ‘F’ and ‘E’ interventions: A formative research study in Oromia, Ethiopia

PLoS Neglected Tropical Diseases News - 9 October 2019 - 9:00pm

by Katie Greenland, Sian White, Katina Sommers, Adam Biran, Matthew J. Burton, Virginia Sarah, Wondu Alemayehu

Background

Trachoma is the leading infectious cause of blindness. However, little is known about the behavioural and environmental determinants of transmission of the causative organism, Chlamydia trachomatis. We conducted formative research in a trachoma hyper-endemic area of Ethiopia to explore the behaviours which are likely to contribute to trachoma transmission and map their determinants.

Methodology/Principal findings

Data on water use, hygiene, defecation, and sleeping arrangements were collected from five communities during the dry and rainy seasons in 2016. Data collection involved direct observation in households (n = 20), interviews with caregivers (n = 20) and focus group discussions (n = 11). Although several behaviours that likely contribute to trachoma transmission were identified, no single behaviour stood out as the dominant contributor. Hygiene practices reflected high levels of poverty and water scarcity. Face washing and soap use varied within and between households, and were associated with other factors such as school attendance. Children’s faces were rarely wiped to remove nasal or ocular discharge, which was not perceived to be socially undesirable. Bathing and laundry were performed infrequently due to the amount of time and water required. Open defecation was a normative practice, particularly for young children. Latrines, when present, were poorly constructed, maintained and used. Young children and parents slept closely together and shared bedding that was infrequently washed.

Conclusions/Significance

Existing norms and enabling factors in this context favour the development of interventions to improve facial cleanliness as more feasible than those that reduce unsafe faeces disposal. Interventions to increase the frequency of bathing and laundry may also be infeasible unless water availability within the home is improved.

Longitudinal evaluation of asymptomatic Leishmania infection in HIV-infected individuals in North-West Ethiopia: A pilot study

PLoS Neglected Tropical Diseases News - 8 October 2019 - 9:00pm

by Johan van Griensven, Saskia van Henten, Bewketu Mengesha, Mekibib Kassa, Emebet Adem, Mengistu Endris Seid, Saïd Abdellati, Wondimu Asefa, Tesfa Simegn, Degnachew Debasu, Tadfe Bogale, Yonas Gedamu, Dorien Van Den Bossche, Wim Adriaensen, Gert Van der Auwera, Lieselotte Cnops, Florian Vogt, Ermias Diro

Background

In endemic regions, asymptomatic Leishmania infection is common. In HIV patients, detection of asymptomatic Leishmania infection could potentially identify those at risk of visceral leishmaniasis (VL). However, data on the prevalence, incidence, and determinants of asymptomatic infection, and the risk of VL are lacking.

Methods

We conducted a cross-sectional survey at a single ART centre, followed by a prospective cohort study amongst HIV-infected adults in HIV care in a district hospital in a VL-endemic area in North-West Ethiopia (9/2015-8/2016). Asymptomatic Leishmania infection was detected using the direct agglutination test (DAT), rK39-rapid diagnostic test (RDT)), PCR on peripheral blood and the KAtex urine antigen test, and defined as positivity on any Leishmania marker. All individuals were followed longitudinally (irrespective of the Leishmania test results). Risk factors for asymptomatic Leishmania infection were determined using logistic regression.

Results

A total of 534 HIV-infected individuals enrolled in HIV care were included in the study. After excluding 13 patients with a history of VL and an 10 patients with incomplete baseline Leishmania tests, 511 were included in analysis. The median age was 38 years (interquartile range (IQR) 30–45), 62.6% were male. The median follow-up time was 12 months (IQR 9–12). No deaths were reported during the study period. Most (95.5%) were on antiretroviral treatment at enrolment, for a median of 52 months (IQR 27–79). The median CD4 count at enrolment was 377 cells/mm3 (IQR 250–518). The baseline prevalence of Leishmania infection was 12.8% in males and 4.2% in females. Overall, 7.4% tested positive for rK39, 4.3% for DAT, 0.2% for PCR and 0.2% for KAtex. Independent risk factors for a prevalent infection were male sex (odds ratio (OR) 3.2; 95% confidence intervals (CI) 14–7.0) and concurrent malaria infection (OR 6.1; 95% CI 1.9–18.9). Amongst the 49 prevalent (baseline) infections with further follow-up, the cumulative incidence of losing the Leishmania markers by one year was 40.1%. There were 36 incident infections during the course of the study, with a cumulative one-year risk of 9.5%. Only one case of VL was detected during follow-up.

Conclusions

We found a high prevalence of asymptomatic Leishmania infection, persisting in most cases. The incidence was more modest and overt VL was rare. Larger and longer studies with more complete follow-up may help to decide whether a test and treat strategy would be justified in this context.

Trial registration

ClinicalTrials.gov NCT02839603

A peridomestic <i>Aedes malayensis</i> population in Singapore can transmit yellow fever virus

PLoS Neglected Tropical Diseases News - 7 October 2019 - 9:00pm

by Elliott F. Miot, Fabien Aubry, Stéphanie Dabo, Ian H. Mendenhall, Sébastien Marcombe, Cheong H. Tan, Lee C. Ng, Anna-Bella Failloux, Julien Pompon, Paul T. Brey, Louis Lambrechts

The case-fatality rate of yellow fever virus (YFV) is one of the highest among arthropod-borne viruses (arboviruses). Although historically, the Asia-Pacific region has remained free of YFV, the risk of introduction has never been higher due to the increasing influx of people from endemic regions and the recent outbreaks in Africa and South America. Singapore is a global hub for trade and tourism and therefore at high risk for YFV introduction. Effective control of the main domestic mosquito vector Aedes aegypti in Singapore has failed to prevent re-emergence of dengue, chikungunya and Zika viruses in the last two decades, raising suspicions that peridomestic mosquito species untargeted by domestic vector control measures may contribute to arbovirus transmission. Here, we provide empirical evidence that the peridomestic mosquito Aedes malayensis found in Singapore can transmit YFV. Our laboratory mosquito colony recently derived from wild Ae. malayensis in Singapore was experimentally competent for YFV to a similar level as Ae. aegypti controls. In addition, we captured Ae. malayensis females in one human-baited trap during three days of collection, providing preliminary evidence that host-vector contact may occur in field conditions. Finally, we detected Ae. malayensis eggs in traps deployed in high-rise building areas of Singapore. We conclude that Ae. malayensis is a competent vector of YFV and re-emphasize that vector control methods should be extended to target peridomestic vector species.

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