RSS news feeds

Epidemiological surveillance of schistosomiasis outbreak in Corsica (France): Are animal reservoir hosts implicated in local transmission?

PLoS Neglected Tropical Diseases News - 24 June 2019 - 9:00pm

by Ana Oleaga, Olivier Rey, Bruno Polack, Sébastien Grech-Angelini, Yann Quilichini, Ricardo Pérez-Sánchez, Pascal Boireau, Stephen Mulero, Aimé Brunet, Anne Rogon, Isabelle Vallée, Julien Kincaid-Smith, Jean-François Allienne, Jérôme Boissier

Environmental and anthropogenic changes are expected to promote emergence and spread of pathogens worldwide. Since 2013, human urogenital schistosomiasis is established in Corsica island (France). Schistosomiasis is a parasitic disease affecting both humans and animals. The parasite involved in the Corsican outbreak is a hybrid form between Schistosoma haematobium, a human parasite, and Schistosoma bovis, a livestock parasite. S. bovis has been detected in Corsican livestock few decades ago raising the questions whether hybridization occurred in Corsica and if animals could behave as a reservoir for the recently established parasite lineage. The latter hypothesis has huge epidemiological outcomes since the emergence of a zoonotic lineage of schistosomes would be considerably harder to control and eradicate the disease locally and definitively needs to be verified. In this study we combined a sero-epidemiological survey on ruminants and a rodent trapping campaign to check whether schistosomes could shift on vertebrate hosts other than humans. A total of 3,519 domesticated animals (1,147 cattle; 671 goats and 1,701 sheep) from 160 farms established in 14 municipalities were sampled. From these 3,519 screened animals, 17 were found to be serologically positive but were ultimately considered as false positive after complementary analyses. Additionally, our 7-day extensive rodent trapping (i.e. 1,949 traps placed) resulted in the capture of a total of 34 rats (Rattus rattus) and 4 mice (Mus musculus). Despite the low number of rodents captured, molecular diagnostic tests showed that two of them have been found to be infected by schistosomes. Given the low abundance of rodents and the low parasitic prevalence and intensity among rodents, it is unlikely that neither rats nor ruminants play a significant role in the maintenance of schistosomiasis outbreak in Corsica. Finally, the most likely hypothesis is that local people initially infected in 2013 re-contaminated the river during subsequent summers, however we cannot definitively rule out the possibility of an animal species acting as reservoir host.

Chronic hepatitis B virus infection drives changes in systemic immune activation profile in patients coinfected with <i>Plasmodium vivax</i> malaria

PLoS Neglected Tropical Diseases News - 24 June 2019 - 9:00pm

by Luís A. B. Cruz, Marina O. A. Moraes, Matheus R. Queiroga-Barros, Kiyoshi F. Fukutani, Manoel Barral-Netto, Bruno B. Andrade

Background

Plasmodium vivax and Hepatitis B virus (HBV) are globally outspread in similar geographic regions. The concurrence of both infections and its association with some degree of protection against symptomatic and/or severe vivax malaria has been already described. Nevertheless, data on how host response to both pathogens undermines the natural progression of the malarial infection are scarce. Here, a large cohort of vivax malaria and HBV patients is retrospectively analyzed in an attempt to depict how inflammatory characteristics could be potentially related to the protection to severe malaria in coinfection.

Methods

A retrospective analysis of a databank containing 601 individuals from the Brazilian Amazon, including 179 symptomatic P. vivax monoinfected patients, 145 individuals with asymptomatic P. vivax monoinfection, 28 P. vivax-HBV coinfected patients, 29 HBV monoinfected subjects and 165 healthy controls, was performed. Data on plasma levels of multiple chemokines, cytokines, acute phase proteins, hepatic enzymes, bilirubin and creatinine were analyzed to describe and compare biochemical profiles associated to each type of infection.

Results

Coinfected individuals predominantly presented asymptomatic malaria, referred increased number of previous malaria episodes than symptomatic vivax-monoinfected patients, and were predominantly younger than asymptomatic vivax-monoinfected individuals. Coinfection was hallmarked by substantially elevated concentrations of interleukin (IL)-10 and heightened levels of C-C motif chemokine ligand (CCL)2. Correlation matrices showed that coinfected individuals presented a distinct biomarker profile when compared to asymptomatic or symptomatic P. vivax patients, or HBV-monoinfected individuals. Parasitemia could distinguish coinfected from symptomatic or asymptomatic P. vivax-monoinfected patients. HBV viremia was associated to distinct inflammatory profiles in HBV-monoinfected and coinfected patients.

Conclusion

The findings demonstrate a distinct inflammatory profile in coinfected patients, with characteristics associated with immune responses to both pathogens. These host responses to P. vivax and HBV, in conjunction, could then be potentially associated, if not mainly responsible, for the protection against symptomatic vivax malaria.

Correction: Assessment of trachoma in suspected endemic areas within 16 provinces in mainland China

PLoS Neglected Tropical Diseases News - 24 June 2019 - 9:00pm

by Jialiang Zhao, Silvio Paolo Mariotti, Serge Resnikoff, Yuqin Wang, Shicheng Yu, Mingguang He, Yingchuan Fan, Haidong Zou, Wenfang Zhang, Yading Jia, Lihua Wang, Huaijin Guan, Xiao Xu, Leilei Zhan, Lei An, Quanfu Ye, Ningli Wang

Genetic characteristics of pathogenic <i>Leptospira</i> in wild small animals and livestock in Jiangxi Province, China, 2002–2015

PLoS Neglected Tropical Diseases News - 24 June 2019 - 9:00pm

by Cuicai Zhang, Jianmin Xu, Tinglan Zhang, Haiyan Qiu, Zhenpeng Li, Enmin Zhang, Shijun Li, Yung-Fu Chang, Xiaokui Guo, Xiugao Jiang, Yongzhang Zhu

Background

Leptospirosis is one of the most important neglected tropical bacterial diseases worldwide. However, there is limited information on the genetic diversity and host selectivity of pathogenic Leptospira in wild small mammal populations.

Methodology/Principal findings

Jiangxi Province, located in southern China, is a region highly endemic for leptospirosis. In this study, among a total of 3,531 trapped rodents dominated by Apodemus agrarius (59.7%), 330 Leptospira strains were successfully isolated from six different sites in Jiangxi between 2002 and 2015. Adding 71 local strains from humans, various kinds of livestock and wild animals in Jiangxi, a total of 401 epidemic strains were characterized using 16S rRNA gene senquencing, multilocus sequence typing (MLST) and the microscopic agglutination test (MAT). Among them, the most prevalent serogroup was Icterohaemorrhagiae (61.10%), followed by Javanica (19.20%) and Australis (9.73%); the remaining five serogroups, Canicola, Autumnalis, Grippotyphosa, Hebdomadis and Pomona, accounted for 9.97%. Species identification revealed that 325 were L. interrogans and 76 were L. borgpetersenii. Moreover, L. interrogans was the only pathogenic species in Fuliang and Shanggao and was predominant in Shangrao (95.0%); L. borgpetersenii was the most common in the remaining three sites. Twenty-one sequence types (STs) were identified. Similarly, ST1 and serogroup Icterohaemorrhagiae were most prevalent in Shangrao (86.0% and 86.4%) and Fuliang (90.4% and 90.4%), ST143 and serogroup Javanica in Shangyou (88.5% and 90.4%) and Longnan (73.1% and 73.1%), and ST105 and serogroup Australis in Shanggao (46.3% and 56.1%). Serogroup Icterohaemorhagiae primarily linked to A. agrarius (86.9%), serogroup Canicola to dogs (83.3%). There were significant differences in the distribution of leptospiral species/serogroups/STs prevalence across host species/collected locations among the 394 animal-associated strains (Fisher’s exact test, p<0.001).

Conclusions/Significance

Our study demonstrated high genetic diversity of pathogenic Leptospira strains from wild small animals in Jiangxi from 2002 to 2015. A. agrarius was the most abundantly trapped animal reservoir, and serogroup Icterohaemorrhagiae and ST1 were the most dominant in Jiangxi. Significant geographic variation and host diversity in the distribution of dominant species, STs and serogroups were observed. Moreover, rat-to-human transmission might play a crucial role in the circulation of Leptospirosis in Jiangxi. Details of the serological and molecular characteristics circulating in this region will be essential in implementing prevention and intervention measures to reduce the risk of disease transmission in China. However, phylogenetic analysis of more Leptospira isolates should explore the impact of ecological change on leptospirosis transmission dynamics and investigate how such new knowledge might better impact environmental monitoring for disease control and prevention at a public health level.

Knowledge, perceptions and experiences of trachoma among Maasai in Tanzania: Implications for prevention and control

PLoS Neglected Tropical Diseases News - 24 June 2019 - 9:00pm

by Tara B. Mtuy, Matthew J. Burton, Upendo Mwingira, Jeremiah M. Ngondi, Janet Seeley, Shelley Lees

Background

The Alliance for the Global Elimination of Trachoma has set the target for eliminating trachoma as a public health problem by 2020. However, challenges remain, including socio-cultural issues. Districts in Northern Tanzania, predominantly inhabited by the Maasai ethnic group, remain endemic for trachoma. We explored socio-cultural factors that may impact the elimination of trachoma.

Methods/Findings

This study was nested within a larger ethnographic study of trachoma among Maasai in Northern Tanzania. We used stratified random sampling and semi-structured interviews to examine knowledge and understanding. Interviews were conducted and recorded in Maa, by a native Maa speaking trained interviewer. Transcripts were translated into English. A framework method for a content analysis was used. There was awareness of trachoma and basic symptoms. Yet understanding of etiology and prevention was poor. Trachoma was attributed to pollen, dust, and smoke. Water was recognized as beneficial, but seen as treatment and not prevention. Traditional medicines were most often used for treating conjunctival inflammation, with the most common being a rough leaf used to scratch the inside of the eyelid until it bleeds. Knowledge of mass drug administration (MDA) was inconsistent, although many thought it helped the community, but it was perceived as only for children and the sick. Many participants reported not taking azithromycin and some had no recollection of MDA six months earlier. There was little connection between childhood infection, trichiasis and related blindness. Trichiasis was often seen as a problem of old women, and treated locally by epilation.

Conclusion/Significance

Understanding indigenous knowledge may help guide control programs, tailor them to local contexts, address local beliefs and dispel misunderstandings. There is an essential need to understand the social, cultural and political context of the target community to deliver effective programs. Despite limited knowledge, the community recognized trachoma as a public health problem. Results have implications for disease control programs in other marginalized communities.

<i>M</i>. <i>leprae</i> interacts with the human epidermal keratinocytes, neonatal (HEKn) via the binding of laminin-5 with α-dystroglycan, integrin-β1, or -β4

PLoS Neglected Tropical Diseases News - 24 June 2019 - 9:00pm

by Song-Hyo Jin, Se-Kon Kim, Seong-Beom Lee

Although Mycobacterium leprae (M.leprae) is usually found in macrophages and nerves of the dermis of patients with multibacillary leprosy, it is also present in all layers of the epidermis, basal, suprabasal, prickle cells, and keratin layers. However, the mechanism by which M.leprae invades the dermis remains unknown, whereas the underlying mechanism by which M.leprae invades peripheral nerves, especially Schwann cells, is well defined. M. leprae binds to the α-dystroglycan (DG) of Schwann cells via the interaction of α-DG and laminin (LN) -α2 in the basal lamina, thus permitting it to become attached to and invade peripheral nerves. In the current study, we investigated the issue of how M.leprae is phagocytosed by human epidermal keratinocytes, neonatal (HEKn). LN-5 is the predominant form of laminin in the epidermis and allows the epidermis to be stably attached to the dermis via its interaction with α/β-DG as well as integrins that are produced by keratinocytes. We therefore focused on the role of LN-5 when M. leprae is internalized by HEKn cells. Our results show that M.leprae preferentially binds to LN-5-coated slides and this binding to LN-5 enhances its binding to HEKn cells. The findings also show that pre-treatment with an antibody against α-DG, integrin-β1, or -β4 inhibited the binding of LN-5-coated M.leprae to HEKn cells. These results suggest that M. leprae binds to keratinocytes by taking advantage of the interaction of LN-5 in the basal lamina of the epidermis and a surface receptor of keratinocytes, such as α-DG, integrin-β1, or -β4.

Standardized endocystectomy technique for surgical treatment of uncomplicated hepatic cystic echinococcosis

PLoS Neglected Tropical Diseases News - 21 June 2019 - 9:00pm

by Mohammed Al-Saeedi, Elias Khajeh, Katrin Hoffmann, Omid Ghamarnejad, Marija Stojkovic, Tim F. Weber, Mohammad Golriz, Oliver Strobel, Thomas Junghanss, Markus W. Büchler, Arianeb Mehrabi

Background

Two surgical options are available for cystic echinococcosis (CE). The two principal approaches are radical (resection of the cyst) and conservative (evacuation of the cyst content and partial removal of the cyst capsule). Here, we describe a standardized endocystectomy technique for hepatic echinococcosis.

Subjects and methods

Twenty-one patients (male/female: 4/3; median age: 28 years) with uncomplicated, isolated hepatic CE (cyst stages WHO CE1, 2, 3a, and 3b) that were treated with the standardized endocystectomy described in this paper. Before the operation and during the follow-up period (mean: 33.8 months, median: 24 months), patients underwent clinical and sonographical and/or magnetic resonance imaging assessment during regular visits managed by an interdisciplinary team.

Results

Forty-seven cysts were treated with the standardized endocystectomy technique. The median number of cysts per patient was two (range: 1–8). Nine patients (43%) had a single cystic lesion. The median operation time was 165 minutes and the median intraoperative bleeding volume was 200 mL. The median hospital stay was nine days (range: 6–28 days). Morbidity (Clavien-Dindo III) occurred in four patients (19%). No mortality and no recurrence were found during the median follow-up time of 24 months.

Conclusions

The standardized endocystectomy technique presented is a safe procedure with acceptable morbidity, no mortality, and without recurrences in our patient series. Important components of our CE management are interdisciplinary patient care, adequate diagnostic work-ups, and regular pre- and postoperative visits, including long-term follow-up for early and reliable capture of recurrences.

Functional illiteracy burden in soil-transmitted helminth (STH) endemic regions of the Philippines: An ecological study and geographical prediction for 2017

PLoS Neglected Tropical Diseases News - 21 June 2019 - 9:00pm

by Kei Owada, Mark Nielsen, Colleen L. Lau, Laith Yakob, Archie C. A. Clements, Lydia Leonardo, Ricardo J. Soares Magalhães

Background

Soil-transmitted helminth (STH) infections remain highly endemic across the Philippines, and are believed to be important contributors to delayed cognitive development of school-aged children. Identification of communities where children are at risk of functional illiteracy is important for the attainment of Sustainable Development Goals target for literacy. We aimed to quantify the associations between the spatial variation of STH infections and functional literacy indicators adjusting for other important contributors, and identify priority areas in the Philippines in need of interventions.

Methodology/Principal findings

We used data from 11,313 school-aged children on functional literacy indicators collected in 2008. Nested fixed-effects multinomial regression models were built to determine associations between STH endemicity and geographical distribution of functional literacy, adjusting for demographics, household level variables, and the prevalence of malaria. Bayesian multinomial geostatistical models were built to geographically predict the prevalence of each level of functional literacy. The number of school-aged children belonging to each of the functional literacy indicator classes was forecast for 2017.We estimated 4.20% of functional illiteracy burden among school-aged children in Mindanao might be averted by preventing T. trichiura infections. Areas predicted with the highest prevalence of functional illiteracy were observed in localised areas of the eastern region of the Visayas, and the south-eastern portion of Mindanao.

Conclusions/Significance

The study demonstrates significant geographical variation in burden of functional illiteracy in school-aged children associated with STH infections suggesting that targeted helminth control could potentially promote the development of cognitive function of school-aged children in the Philippines. The benefits of a spatially targeted strategy should be tested by future studies.

Assessing dengue control in Tokyo, 2014

PLoS Neglected Tropical Diseases News - 21 June 2019 - 9:00pm

by Baoyin Yuan, Hyojung Lee, Hiroshi Nishiura

Background

In summer 2014, an autochthonous outbreak of dengue occurred in Tokyo, Japan, in which Yoyogi Park acted as the focal area of transmission. Recognizing the outbreak, concerted efforts were made to control viral spread, which included mosquito control, public announcement of the outbreak, and a total ban on entering the park. We sought to assess the effectiveness of these control measures.

Methodology/Principal findings

We used a mathematical model to describe the transmission dynamics. Using dates of exposure and illness onset, we categorized cases into three groups according to the availability of these datasets. The infection process was parametrically modeled by generation, and convolution of the infection process and the incubation period was fitted to the data. By estimating the effective reproduction number, we determined that the effect of dengue risk communication together with mosquito control from 28 August 2014 was insufficiently large to lower the reproduction number to below 1. However, once Yoyogi Park was closed on 4 September, the value of the effective reproduction number began to fall below 1, and the associated relative reduction in the effective reproduction number was estimated to be 20%–60%. The mean incubation period was an estimated 5.8 days.

Conclusions/Significance

Regardless of the assumed number of generations of cases, the combined effect of mosquito control, risk communication, and park closure appeared to be successful in interrupting the chain of dengue transmission in Tokyo.

The inappropriate use of antibiotics in hospitalized dengue virus-infected children with presumed concurrent bacterial infection in teaching and private hospitals in Bandung, Indonesia

PLoS Neglected Tropical Diseases News - 21 June 2019 - 9:00pm

by Riyadi Adrizain, Djatnika Setiabudi, Alex Chairulfatah

Background

Dengue virus infection (DVI) among children is a leading cause of hospitalization in endemic areas. Hospitalized patients are at risk of receiving unnecessary antibiotics.

Methods

A retrospective medical review analysis study was conducted to evaluate the prevalence, indication, and choice of antibiotics given to hospitalized patients less than 15 years of age with DVI in two different hospital settings (teaching and private hospitals) in the Municipality of Bandung. Epidemiological, clinical, and laboratory data were obtained using a pre-tested standardized questionnaire from patients’ medical records admitted from January 1 to December 31, 2015.

Results

There were 537 (17.5%) out of 3078 cases who received antibiotics. Among 176 cases admitted to the teaching hospitals, presumed bacterial upper respiratory tract infection (URTI) and typhoid fever were found in 1 (0.6%) case and 6 (0.3%) cases. In private hospitals among 2902 cases, presumed bacterial URTI was found in 324 (11.2%) cases, typhoid fever in 188 (6.5%) cases and urinary tract infection (UTI) in 18 (0.6%) cases. The prevalence of URTI and typhoid fever were significantly lower in the teaching hospitals compared to the private hospitals (p<0.0001 and p<0.05 respectively). The diagnosis of URTI in both teaching and private hospitals was merely based on clinical findings. Amoxicillin was given to 1 patient in the teaching hospitals; the 3rd generation of cephalosporins, mostly intravenous, were given in 247 (67%) cases in private hospitals. The diagnosis of typhoid fever in the teaching hospitals was based on culture in 1 (16.7%) and reactive IgM anti-Salmonella in 5 (83.3%) cases while in the private hospitals, they were based on reactive IgM anti-Salmonella in 13 (6.5%) cases, single Widal test in 61 (32.5%), and without laboratory confirmation in 114 (60.6%) cases. Most of the cases in both hospital settings were treated mostly with 3rd generation cephalosporin. The diagnosis of UTI was based on positive leucocyte esterase and nitrite in urine dipstick test in 7 (38.9%) and leucocyturia alone in 11 (61.1%) cases and was treated with 3rd generation in 15 (83.3%) cases, amoxicillin, chloramphenicol and clarithromycin, each in 1 (5.6%) case.

Conclusion

The use of antibiotics in private hospitals was inappropriate in most cases while the use of antibiotics in the teaching hospital was more accountable. This study indicated that interventions, such as the implementation of the antibiotics stewardship program, are needed especially in private hospitals to reduce inappropriate use of antibiotics.

Further insight into the geographic distribution of <i>Leishmania</i> species in Peru by cytochrome <i>b</i> and mannose phosphate isomerase gene analyses

PLoS Neglected Tropical Diseases News - 20 June 2019 - 9:00pm

by Hirotomo Kato, Abraham G. Cáceres, Chisato Seki, Carmen Rosa Silupu García, Carlos Holguín Mauricci, Salvadora Concepción Castro Martínez, Dafne Moreno Paico, Josefa Leila Castro Muniz, Lucinda Doriz Troyes Rivera, Zoila Isabel Villegas Briones, Silvia Guerrero Quincho, Guísela Lucy Sulca Jayo, Edwin Tineo Villafuerte, Carlos Manrique de Lara Estrada, Fernando Rafael Arias, Fredy Santiago Passara, Nancy Ruelas Llerena, Makoto Kubo, Ahmed Tabbabi, Daisuke S. Yamamoto, Yoshihisa Hashiguchi

To obtain further insight into geographic distribution of Leishmania species in Peru, a countrywide survey, including central to southern rainforest areas where information on causative parasite species is limited, was performed based on cytochrome b (cyt b) and mannose phosphate isomerase (mpi) gene analyses. A total of 262 clinical samples were collected from patients suspected of cutaneous leishmaniasis (CL) in 28 provinces of 13 departments, of which 99 samples were impregnated on FTA (Flinders Technology Associates) cards and 163 samples were Giemsa-stained smears. Leishmania species were successfully identified in 83 (83.8%) of FTA-spotted samples and 59 (36.2%) of Giemsa-stained smear samples. Among the 142 samples identified, the most dominant species was Leishmania (Viannia) braziliensis (47.2%), followed by L. (V.) peruviana (26.1%), and others were L. (V.) guyanensis, L. (V.) lainsoni, L. (V.) shawi, a hybrid of L. (V.) braziliensis and L. (V.) peruviana, and Leishmania (Leishmania) amazonensis. Besides the present epidemiological observations, the current study provided the following findings: 1) A hybrid of L. (V.) braziliensis and L. (V.) peruviana is present outside the Department of Huanuco, the only place reported, 2) Many cases of CL due to L. (V.) lainsoni, an uncommon causative species in Peru, were observed, and 3) L. (V.) shawi is widely circulating in southern Amazonian areas in Peru.

Emergence of phylogenetically diverse and fluoroquinolone resistant <i>Salmonella</i> Enteritidis as a cause of invasive nontyphoidal <i>Salmonella</i> disease in Ghana

PLoS Neglected Tropical Diseases News - 20 June 2019 - 9:00pm

by Cassandra Aldrich, Hassan Hartman, Nicholas Feasey, Marie Anne Chattaway, Denise Dekker, Hassan M. Al-Emran, Lesley Larkin, Jacquelyn McCormick, Nimako Sarpong, Simon Le Hello, Yaw Adu-Sarkodie, Ursula Panzner, Se Eun Park, Justin Im, Florian Marks, Jürgen May, Timothy J. Dallman, Daniel Eibach

Background

Salmonella enterica serovar Enteritidis is a cause of both poultry- and egg-associated enterocolitis globally and bloodstream-invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa (sSA). Distinct, multi-drug resistant genotypes associated with iNTS disease in sSA have recently been described, often requiring treatment with fluoroquinolone antibiotics. In industrialised countries, antimicrobial use in poultry production has led to frequent fluoroquinolone resistance amongst globally prevalent enterocolitis-associated lineages.

Methodology/Principal findings

Twenty seven S. Enteritidis isolates from patients with iNTS disease and two poultry isolates, collected between 2007 and 2015 in the Ashanti region of Ghana, were whole-genome sequenced. These isolates, notable for a high rate of diminished ciprofloxacin susceptibility (DCS), were placed in the phyletic context of 1,067 sequences from the Public Health England (PHE) S. Enteritidis genome database to understand whether DCS was associated with African or globally-circulating clades of S. Enteritidis. Analysis showed four of the major S. Enteritidis clades were represented, two global and two African. All thirteen DCS isolates, containing a single gyrA mutation at codon 87, belonged to a global PT4-like clade responsible for epidemics of poultry-associated enterocolitis. Apart from two DCS isolates, which clustered with PHE isolates associated with travel to Spain and Brazil, the remaining DCS isolates, including one poultry isolate, belonged to two monophyletic clusters in which gyrA 87 mutations appear to have developed within the region.

Conclusions/Significance

Extensive phylogenetic diversity is evident amongst iNTS disease-associated S. Enteritidis in Ghana. Antimicrobial resistance profiles differed by clade, highlighting the challenges of devising empirical sepsis guidelines. The detection of fluoroquinolone resistance in phyletically-related poultry and human isolates is of major concern and surveillance and control measures within the region’s burgeoning poultry industry are required to protect a human population at high risk of iNTS disease.

Cholera prevention and control in refugee settings: Successes and continued challenges

PLoS Neglected Tropical Diseases News - 20 June 2019 - 9:00pm

by Kerry Shannon, Marisa Hast, Andrew S. Azman, Dominique Legros, Heather McKay, Justin Lessler

"Those who died are the ones that are cured". Walking the political tightrope of Nodding Syndrome in northern Uganda: Emerging challenges for research and policy

PLoS Neglected Tropical Diseases News - 20 June 2019 - 9:00pm

by Julia Irani, Joseph Rujumba, Amos Deogratius Mwaka, Jesca Arach, Denis Lanyuru, Richard Idro, Rene Gerrets, Koen Peeters Grietens, Sarah O’Neill

Background

Nodding Syndrome was first reported from Tanzania in the 1960s but appeared as an epidemic in Northern Uganda in the 1990s during the LRA civil war. It is characterized by repetitive head nodding, often followed by other types of seizures, developmental retardation and growth faltering with onset occurring in children aged 5–15 years. More than 50 years after the first reports, the aetiology remains unknown and there is still no cure. The recent hypothesis that Nodding Syndrome is caused by onchocerciasis also increases the relevance of onchocerciasis control. Northern Uganda, with its unique socio-political history, adds challenges to the prevention and treatment for Nodding Syndrome. This article aims to show how and why Nodding Syndrome has been politicised in Uganda; how this politicisation has affected health interventions including research and dissemination; and, the possible implications this can have for disease prevention and treatment.

Methodology

Ethnographic research methods were used triangulating in-depth interviews, focus group discussions, informal conversations and participant observation, for an understanding of the various stakeholders’ perceptions of Nodding Syndrome and how these perceptions impact future interventions for prevention, treatment and disease control.

Principal findings

Distrust towards the government was a sentiment that had developed in Northern Uganda over several decades of war and was particularly linked to the political control and ethnic divisions between the north and south. This coincided with the sudden appearance of Nodding Syndrome, an unknown epidemic disease of which the cause could not be clearly identified and optimal treatment had not clearly been established. Additionally, the dissemination of the inconclusive results of research conducted in the area lacked sufficient community involvement which further fueled this political distrust. Disease perceptions revolved around rumours that the entire Acholi ethnic group of the north would be annihilated, or that international researchers were making money by stealing study samples. This discouraged some community members from participating in research or from accepting the mass drug administration of ivermectin for prevention and treatment of onchocerciasis. Such rumour and distrust led to suspicions concerning the integrity of the disseminated results, which may negatively impact future disease management and control interventions.

Conclusions and recommendations

Trust must be built up gradually through transparency and by de-politicising interventions. This can be done by engaging the community at regular intervals during research and data collection and the dissemination of results in addition to involvement during service delivery for prevention and treatment. Maintaining a regular feedback loop with the community will help control rumours, build trust, and improve the preparations for adequate dissemination.

<i>Strongyloides stercoralis</i>: Spatial distribution of a highly prevalent and ubiquitous soil-transmitted helminth in Cambodia

PLoS Neglected Tropical Diseases News - 20 June 2019 - 9:00pm

by Armelle Forrer, Virak Khieu, Penelope Vounatsou, Paiboon Sithithaworn, Sirowan Ruantip, Rekol Huy, Sinuon Muth, Peter Odermatt

Background

Strongyloides stercoralis is a neglected soil-transmitted helminth that occurs worldwide, though it is particularly endemic in tropical and subtropical areas. It can cause long-lasting and potentially fatal infections due to its ability to replicate within its host. S. stercoralis causes gastrointestinal and dermatological morbidity. The objective of this study was to assess the S. stercoralis infection risk and, using geostatistical models, to predict its geographical distribution in Cambodia.

Methodology / Principal findings

A nation-wide, community-based parasitological survey was conducted among the Cambodian population, aged 6 years and older. S. stercoralis was diagnosed using a serological diagnostic test that detects IgG antibodies in urine. Data on demography, hygiene and knowledge about helminth infection were collected. S. stercoralis prevalence among 7,246 participants with a complete data record was 30.5%, ranging from 10.9% to 48.2% across provinces. The parasite was ubiquitous in Cambodia; only five south-eastern provinces had prevalence rates below 20%. Infection risk increased with age for both men and women, although girls under the age of 13 and women aged 50 years and over had lower odds of infection than their male counterparts. Open defecation was associated with higher odds of infection, while having some knowledge of the health problems caused by worms was a protective factor. Infection risk was positively associated with nighttime maximum temperature, minimum rainfall, and distance to water; it was negatively associated with land occupied by rice fields.

Conclusions / Significance

S. stercoralis infection is rampant in Cambodia. Control programs delivering ivermectin are needed to manage the parasite. However, the high cost of this drug in Cambodia currently precludes the implementation of control initiatives. Donations, subsidies or affordable generics are needed so that S. stercoralis, which infects almost a third of the Cambodian population, can be addressed through an adequate control program.

Comparative performance of lateral flow immunochromatography, iELISA and Rose Bengal tests for the diagnosis of cattle, sheep, goat and swine brucellosis

PLoS Neglected Tropical Diseases News - 19 June 2019 - 9:00pm

by Amahyel M. Gusi, Wilson J. Bertu, M. Jesús de Miguel, Lucía Dieste-Pérez, Henk L. Smits, Reuben A. Ocholi, José M. Blasco, Ignacio Moriyón, Pilar M. Muñoz

Background

Brucellosis is a world-wide extended zoonosis that causes a grave problem in developing economies. Animal vaccination and diagnosis are essential to control brucellosis, and the need for accurate but also simple and low-cost tests that can be implemented in low-infrastructure laboratories has been emphasized.

Methodology

We evaluated bovine, sheep, goat and swine lateral flow immunochromatography assay kits (LFA), the Rose Bengal test (RBT) and a well-validated protein G indirect ELISA (iELISA) using sera of Brucella culture-positive and unvaccinated brucellosis free livestock. Sera from cattle vaccinated with S19 and RB51 brucellosis vaccines were also tested. Finally, we compared RBT and LFA using sera of white Fulani cattle of unknown bacteriological status from a brucellosis endemic area of Nigeria.

Results and conclusions

Although differences were not statistically significant, RBT showed the highest values for diagnostic sensitivity/specificity in cattle (LFA 96.6/98.8; RBT 98.9/100; and iELISA 96.6/100) and the iELISA yielded highest values in sheep (LFA, 94.0/100; RBT, 92.0/100; iELISA, 100/100), goats (LFA 95.7/96.2; RBT, 97.8/100; iELISA, 100/100) and pigs (LFA, 92.3/100; RBT, 92.3/100; iELISA 100/100). Vaccine S19 administered subcutaneously interfered in all tests but conjunctival application minimized the problem. Although designed not to interfere in serodiagnosis, vaccine RB51 interfered in LFA and iELISA but not in the RBT. We found closely similar apparent prevalence results when testing the Nigerian Fulani cattle by RBT and LFA. Although both RBT and LFA (showing similar diagnostic performance) are suitable for small laboratories in resource-limited areas, RBT has the advantage that a single reagent is useful in all animal species. Considering these advantages, its low cost and that it is also useful for human brucellosis diagnosis, RBT might be a good choice for resource-limited laboratories.

Amazonian Phlebovirus (Bunyaviridae) potentiates the infection of Leishmania (Leishmania) amazonensis: Role of the PKR/IFN1/IL-10 axis

PLoS Neglected Tropical Diseases News - 19 June 2019 - 9:00pm

by Carolina Torturella Rath, Laila Castro Schnellrath, Clarissa R. Damaso, Luciana Barros de Arruda, Pedro Fernando da Costa Vasconcelos, Claudia Gomes, Marcia Dalastra Laurenti, Teresa Cristina Calegari Silva, Áislan de Carvalho Vivarini, Nicolas Fasel, Renata Meirelles Santos Pereira, Ulisses Gazos Lopes

Background

Leishmania parasites are transmitted to vertebrate hosts by phlebotomine sandflies and, in humans, may cause tegumentary or visceral leishmaniasis. The role of PKR (dsRNA activated kinase) and Toll-like receptor 3 (TLR3) activation in the control of Leishmania infection highlights the importance of the engagement of RNA sensors, which are usually involved in the antiviral cell response, in the fate of parasitism by Leishmania. We tested the hypothesis that Phlebovirus, a subgroup of the Bunyaviridae, transmitted by sandflies, would interfere with Leishmania infection.

Methodology/Principal findings

We tested two Phlebovirus isolates, Icoaraci and Pacui, from the rodents Nectomys sp. and Oryzomys sp., respectively, both natural sylvatic reservoir of Leishmania (Leishmania) amazonensis from the Amazon region. Phlebovirus coinfection with L. (L.) amazonensis in murine macrophages led to increased intracellular growth of L. (L.) amazonensis. Further studies with Icoaraci coinfection revealed the requirement of the PKR/IFN1 axis on the exacerbation of the parasite infection. L. (L.) amazonensis and Phlebovirus coinfection potentiated PKR activation and synergistically induced the expression of IFNβ and IL-10. Importantly, in vivo coinfection of C57BL/6 mice corroborated the in vitro data. The exacerbation effect of RNA virus on parasite infection may be specific because coinfection with dengue virus (DENV2) exerted the opposite effect on parasite load.

Conclusions

Altogether, our data suggest that coinfections with specific RNA viruses shared by vectors or reservoirs of Leishmania may enhance and sustain the activation of host cellular RNA sensors, resulting in aggravation of the parasite infection. The present work highlights new perspectives for the investigation of antiviral pathways as important modulators of protozoan infections.

Identification of positively selected genes in human pathogenic treponemes: Syphilis-, yaws-, and bejel-causing strains differ in sets of genes showing adaptive evolution

PLoS Neglected Tropical Diseases News - 19 June 2019 - 9:00pm

by Denisa Maděránková, Lenka Mikalová, Michal Strouhal, Šimon Vadják, Ivana Kuklová, Petra Pospíšilová, Lenka Krbková, Pavlína Koščová, Ivo Provazník, David Šmajs

Background

Pathogenic treponemes related to Treponema pallidum are both human (causing syphilis, yaws, bejel) and animal pathogens (infections of primates, venereal spirochetosis in rabbits). A set of 11 treponemal genome sequences including those of five Treponema pallidum ssp. pallidum (TPA) strains (Nichols, DAL-1, Mexico A, SS14, Chicago), four T. p. ssp. pertenue (TPE) strains (CDC-2, Gauthier, Samoa D, Fribourg-Blanc), one T. p. ssp. endemicum (TEN) strain (Bosnia A) and one strain (Cuniculi A) of Treponema paraluisleporidarum ecovar Cuniculus (TPeC) were tested for the presence of positively selected genes.

Methodology/Principal findings

A total of 1068 orthologous genes annotated in all 11 genomes were tested for the presence of positively selected genes using both site and branch-site models with CODEML (PAML package). Subsequent analyses with sequences obtained from 62 treponemal draft genomes were used for the identification of positively selected amino acid positions. Synthetic biotinylated peptides were designed to cover positively selected protein regions and these peptides were tested for reactivity with the patient's syphilis sera. Altogether, 22 positively selected genes were identified in the TP genomes and TPA sets of positively selected genes differed from TPE genes. While genetic variability among TPA strains was predominantly present in a number of genetic loci, genetic variability within TPE and TEN strains was distributed more equally along the chromosome. Several syphilitic sera were shown to react with some peptides derived from the protein sequences evolving under positive selection.

Conclusions/Significance

The syphilis-, yaws-, and bejel-causing strains differed relative to sets of positively selected genes. Most of the positively selected chromosomal loci were identified among the TPA treponemes. The local accumulation of genetic variability suggests that the diversification of TPA strains took place predominantly in a limited number of genomic regions compared to the more dispersed genetic diversity differentiating TPE and TEN strains. The identification of positively selected sites in tpr genes and genes encoding outer membrane proteins suggests their role during infection of human and animal hosts. The driving force for adaptive evolution at these loci thus appears to be the host immune response as supported by observed reactivity of syphilitic sera with some peptides derived from protein sequences showing adaptive evolution.

Potential animal reservoirs (dogs and bats) of human visceral leishmaniasis due to <i>Leishmania infantum</i> in French Guiana

PLoS Neglected Tropical Diseases News - 19 June 2019 - 9:00pm

by Hacène Medkour, Bernard Davoust, François Dulieu, Laurent Maurizi, Thierry Lamour, Jean-Lou Marié, Oleg Mediannikov

In French Guiana, cutaneous leishmaniasis is highly endemic, whereas no autochthonous case of visceral leishmaniasis have been reported so far. However, due to its proximity to Brazil which is highly endemic for visceral leishmaniasis, and the high transboundary population flow, an epidemiological challenge could arise at any time. As an overseas department and region and the largest outermost region of the European Union, epidemiological surveillance of visceral leishmaniasis is of great importance. Our study aimed to investigate the presence of Leishmania spp. in domestic (dogs) and sylvatic (bats) animals from French Guiana. Over the 2008–2018 period, samples from 349 animals were collected. They included blood from 179 autochthonous dogs and 59 bats, spleen samples from 33 bats and, blood from 78 military working dogs (MWD) collected before their departure from continental France and at the end of their four-month stay in French Guiana. Samples were screened using real-time polymerase chain reaction (qPCR) assays targeting Leishmania DNA followed by sequencing of 18S rRNA, kDNA and ITS2 genes. L. infantum was detected in 2.3% (8/349) of animals with 1.7% (3/179) of autochthonous dogs, 5.1% (4/78) of MWD returning from French Guiana, whereas they were negative before their departure. One of them dates back to 2012. All these dogs were positive for serological tests. In addition, L. infantum DNA was detectable in one bat spleen sample, belonging to Carollia perspicillata species. We report here for the first time an infection with L. infantum in dogs and bat from French Guiana. Our results suggest the existence of potential reservoir and transmission cycle for visceral leishmaniasis, at least since 2012, which was unknown in this territory until now. Further studies are needed to determine how these animals were infected and which vectors are involved in the transmission in this area.

A biosafety level-2 dose-dependent lethal mouse model of spotted fever rickettsiosis: <i>Rickettsia parkeri</i> Atlantic Rainforest strain

PLoS Neglected Tropical Diseases News - 19 June 2019 - 9:00pm

by Andrés F. Londoño, Nicole L. Mendell, David H. Walker, Donald H. Bouyer

Background

The species of the Rickettsia genus are separated into four groups: the ancestral group, typhus group, transitional group and spotted fever group. Rickettsia parkeri, a spotted fever group Rickettsia, has been reported across the American continents as infecting several tick species and is associated with a relatively mild human disease characterized by eschar formation at the tick feeding site, regional lymphadenopathy, fever, myalgia and rash. Currently, there are several mouse models that provide good approaches to study the acute lethal disease caused by Rickettsia, but these models can only be performed in an animal biosafety level 3 laboratory. We present an alternative mouse model for acute lethal rickettsial disease, using R. parkeri Atlantic Rainforest strain and C3H/HeN mice, with the advantage that this model can be studied in an animal biosafety level 2 laboratory.

Principal findings

In the C3H/HeN mouse model, we determined that infection with 1x106 and 1x107 viable R. parkeri Atlantic Rainforest strain organisms produced dose-dependent severity, whereas infection with 1x108 viable bacteria resulted in a lethal illness. The animals became moribund on day five or six post-infection. The lethal disease was characterized by ruffled fur, erythema, labored breathing, decreased activity, and hunched posture, which began on day three post-infection (p.i.) and coincided with the peak bacterial loads. Significant splenomegaly (on days three and five p.i.), neutrophilia (on days three and five p.i.), and thrombocytopenia (on days one, three and five p.i.) were observed.

Significance

Since R. parkeri is used at biosafety level 2, the greatest advantage of this inbred mouse model is the ability to investigate immunity and pathogenesis of rickettsiosis with all the tools available at biosafety level 2.

Pages