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Inadequate knowledge about snakebite envenoming symptoms and application of harmful first aid methods in the community in high snakebite incidence areas of Myanmar

PLoS Neglected Tropical Diseases News - 15 February 2019 - 10:00pm

by Mohammad Afzal Mahmood, Dale Halliday, Robert Cumming, Khin Thida Thwin, Mya Myitzu, Julian White, Sam Alfred, David A. Warrell, David Bacon, Win Naing, Htay Aung, Myat Myat Thein, Nyein Nyein Chit, Sara Serhal, Myat Thet Nwe, Pyae Phyo Aung, Chen Au Peh

Introduction

Every year millions of people in developing countries suffer from snakebite, causing a large number of deaths and long term complications. Prevention and appropriate first aid could reduce the incidence and improve the health outcomes for those who suffer bites. However, many communities where snakebite is a major issue suffer from a lack of information about prevention and first aid measures that a family or community member could take to prevent severe envenoming, complications and poor outcomes. Myanmar suffers from a high burden of snakebites with a large number of deaths. As part of a health services and community development program, a community survey was conducted to identify communities’ knowledge about snakebite and their sequelae, and knowledge and practice about first aid and health services use.

Method

4,276 rural residents of Kyaukse and Madaya townships in the Mandalay region were recruited by cluster sampling, involving random selection of 144 villages and random sampling of 30 households from each village. One adult member of each household was interviewed using a structured questionnaire.

Results

The incidence of snakebite was 116/100,000 people. Respondents reported 15 different types of snakes in the area, with Russell’s Viper, Cobra and Green snakes as the most common. 88% of the people informed that working in the fields and forests was when most of the bites occur. A majority knew about snakebite prevention methods such as wearing long boots. However, only a few people knew about the specific symptoms caused by snakebites. Only 39% knew about the correct methods of first aid. More than 60% mentioned tourniquet as a first aid method, though this may cause significant complications such as ischaemia of the limb. 88% said that they would take a snakebite victim to a government hospital, and 58% mentioned availability of antivenom as the reason for doing this. At the same time, the majority mentioned that traditional methods existed for first aid and treatment and 25% mentioned at least one harmful traditional method as an effective measure that they might use.

Conclusion

The community is aware of snakebites as a major public health issue and know how to prevent them. However, the high incidence of snakebites point to lack of application of preventive methods. The community recognise the need for treatment with antivenom. However, inadequate knowledge about appropriate first aid methods, and a reliance on using tourniquets require a targeted education program. Existing knowledge in communities, albeit insufficient, provides a good starting point for mass media educational campaigns.

Spatio-temporal characterization of <i>Trypanosoma cruzi</i> infection and discrete typing units infecting hosts and vectors from non-domestic foci of Chile

PLoS Neglected Tropical Diseases News - 15 February 2019 - 10:00pm

by Camila Ihle-Soto, Eduardo Costoya, Juana P. Correa, Antonella Bacigalupo, Berenice Cornejo-Villar, Viviana Estadella, Aldo Solari, Sylvia Ortiz, Héctor J. Hernández, Carezza Botto-Mahan, David E. Gorla, Pedro E. Cattan

Background

Trypanosoma cruzi is a protozoan parasite that is transmitted by triatomine vectors to mammals. It is classified in six discrete typing units (DTUs). In Chile, domestic vectorial transmission has been interrupted; however, the parasite is maintained in non-domestic foci. The aim of this study was to describe T. cruzi infection and DTU composition in mammals and triatomines from several non-domestic populations of North-Central Chile and to evaluate their spatio-temporal variations.

Methodology/Principal findings

A total of 710 small mammals and 1140 triatomines captured in six localities during two study periods (summer/winter) of the same year were analyzed by conventional PCR to detect kDNA of T. cruzi. Positive samples were DNA blotted and hybridized with specific probes for detection of DTUs TcI, TcII, TcV, and TcVI. Infection status was modeled, and cluster analysis was performed in each locality. We detected 30.1% of overall infection in small mammals and 34.1% in triatomines, with higher rates in synanthropic mammals and in M. spinolai. We identified infecting DTUs in 45 mammals and 110 triatomines, present more commonly as single infections; the most frequent DTU detected was TcI. Differences in infection rates among species, localities and study periods were detected in small mammals, and between triatomine species; temporally, infection presented opposite patterns between mammals and triatomines. Infection clustering was frequent in vectors, and one locality exhibited half of the 21 clusters found.

Conclusions/Significance

We determined T. cruzi infection in natural host and vector populations simultaneously in a spatially widespread manner during two study periods. All captured species presented T. cruzi infection, showing spatial and temporal variations. Trypanosoma cruzi distribution can be clustered in space and time. These clusters may represent different spatial and temporal risks of transmission.

Prevalence of Wēnzhōu virus in small mammals in Yunnan Province, China

PLoS Neglected Tropical Diseases News - 15 February 2019 - 10:00pm

by Jinxia Wang, Xinglou Yang, Haizhou Liu, Li Wang, Jihua Zhou, Xi Han, Yan Zhu, Weihong Yang, Hong Pan, Yunzhi Zhang, Zhengli Shi

Background

Mammarenaviruses are associated with human hemorrhagic fever diseases in Africa and America. Recently, a rodent mammarenavirus, Wēnzhōu virus (WENV) and related viruses, have been reported in China, Cambodia, and Thailand. Moreover, in Cambodia, these viruses were suspected to be associated with human disease. In China, Yunnan Province is famous for its abundant animal and plant diversity and is adjacent to several South-eastern Asia countries. Therefore, it is necessary to know whether WENV-related viruses, or other mammarenaviruses, are prevalent in this province.

Methodology/Principal findings

Small mammals were trapped, euthanized, and sampled. Mammarenavirus RNA was detected using a nested reverse transcription polymerase chain reaction (RT-PCR) and quantified by real-time RT-PCR. A total of 1040 small mammals belonging to 13 genera and 26 species were trapped in Yunnan Province. WENV-related mammarenaviruses were detected in 41 rodent liver samples, mainly in brown rats (Rattus norvegicus) and oriental house rats (R. tanezumi).Viral nucleocapsid protein was detected in liver sections by indirect immunofluorescence assay. Full-length-genomes were amplified by RT-PCR and used for phylogenetic analysis with the MEGA package. Recombination analysis was performed using the SimPlot and Recombination Detection Program.

Conclusions/Significance

WENV related viruses circulated in small mammals in Yunnan Province. Whole genome sequence analysis of five selected viral strains showed that these viruses are closely related to WENVs discovered in Asia and form an independent branch in the phylogenetic tree in the WENV clade. Paying attention to investigate the influence of these viruses to public health is essential in the epidemic regions.

Antibody responses to <i>Plasmodium vivax</i> Duffy binding and Erythrocyte binding proteins predict risk of infection and are associated with protection from clinical Malaria

PLoS Neglected Tropical Diseases News - 15 February 2019 - 10:00pm

by Wen-Qiang He, Ahmad Rushdi Shakri, Rukmini Bhardwaj, Camila T. França, Danielle I. Stanisic, Julie Healer, Benson Kiniboro, Leanne J. Robinson, Micheline Guillotte-Blisnick, Christèle Huon, Peter Siba, Alan Cowman, Christopher L. King, Wai-Hong Tham, Chetan E. Chitnis, Ivo Mueller

Background

The Plasmodium vivax Duffy Binding Protein (PvDBP) is a key target of naturally acquired immunity. However, region II of PvDBP, which contains the receptor-binding site, is highly polymorphic. The natural acquisition of antibodies to different variants of PvDBP region II (PvDBPII), including the AH, O, P and Sal1 alleles, the central region III-V (PvDBPIII-V), and P. vivax Erythrocyte Binding Protein region II (PvEBPII) and their associations with risk of clinical P. vivax malaria are not well understood.

Methodology

Total IgG and IgG subclasses 1, 2, and 3 that recognize four alleles of PvDBPII (AH, O, P, and Sal1), PvDBPIII-V and PvEBPII were measured in samples collected from a cohort of 1 to 3 year old Papua New Guinean (PNG) children living in a highly endemic area of PNG. The levels of binding inhibitory antibodies (BIAbs) to PvDBPII (AH, O, and Sal1) were also tested in a subset of children. The association of presence of IgG with age, cumulative exposure (measured as the product of age and malaria infections during follow-up) and prospective risk of clinical malaria were evaluated.

Results

The increase in antigen-specific total IgG, IgG1, and IgG3 with age and cumulative exposure was only observed for PvDBPII AH and PvEBPII. High levels of total IgG and predominant subclass IgG3 specific for PvDBPII AH were associated with decreased incidence of clinical P. vivax episodes (aIRR = 0.56–0.68, P≤0.001–0.021). High levels of total IgG and IgG1 to PvEBPII correlated strongly with protection against clinical vivax malaria compared with IgGs against all PvDBPII variants (aIRR = 0.38, P<0.001). Antibodies to PvDBPII AH and PvEBPII showed evidence of an additive effect, with a joint protective association of 70%.

Conclusion

Antibodies to the key parasite invasion ligands PvDBPII and PvEBPII are good correlates of protection against P. vivax malaria in PNG. This further strengthens the rationale for inclusion of PvDBPII in a recombinant subunit vaccine for P. vivax malaria and highlights the need for further functional studies to determine the potential of PvEBPII as a component of a subunit vaccine for P. vivax malaria.

Soil-transmitted helminth reinfection four and six months after mass drug administration: results from the delta region of Myanmar

PLoS Neglected Tropical Diseases News - 15 February 2019 - 10:00pm

by Julia C. Dunn, Alison A. Bettis, Nay Yee Wyine, Aye Moe Moe Lwin, Aung Tun, Nay Soe Maung, Roy M. Anderson

Background

Mass drug administration (MDA), targeted at school-aged children (SAC) is the method recommended by the World Health Organization for the control of morbidity induced by soil-transmitted helminth (STH) infection in endemic countries. However, MDA does not prevent reinfection between treatment rounds and research suggests that only treating SAC will not be sufficient to bring prevalence to low levels and possibly interrupt transmission of STH. In countries with endemic infection, such as Myanmar, the coverage, who is targeted, and rates of reinfection will determine how effective MDA is in suppressing transmission in the long-term.

Methods/principal findings

In this paper, data from an epidemiological study on STH, comprising three surveys conducted between June 2015 and June 2016 in the delta region of Myanmar, are analysed to determine how STH prevalence and intensity in the study community changes over the course of a year, including reinfection after two MDA rounds in which the whole study sample (all age groups, n = 523) were treated with albendazole. Prevalence in the first survey (August 2015) was 27.92% for any STH, 5.54% for Ascaris lumbricoides, 17.02% for Trichuris trichiura and 9.75% for hookworm. Over the year (survey one to survey three), prevalence of any STH decreased by 8.99% (P < 0.001) and mean EPG significantly decreased for T. trichiura (P < 0.01) and hookworm (P < 0.001). Risk ratios (RRs) for a four-month reinfection period (August to December) were statistically significant and were below one, indicating that STH prevalence had not bounced back to the prevalence levels recorded immediately prior to the last round of treatment (any STH RR = 0.67, 95% CI 0.56–0.81; A. lumbricoides RR = 0.31, 95% CI 0.16–0.59; T. trichiura RR = 0.70, 95% CI 0.55–0.88; hookworm RR = 0.69, 95% CI 0.50–0.95). The only statistically significant RR for the six-month reinfection period (December to June) was for A. lumbricoides infection in SAC (RR = 2.67, 95% CI 1.37–5.21). All six-month RRs were significantly higher than four-month RRs (P < 0.05). Evidence of predisposition to infection (low and high), as measured by the Kendall Tau-b statistic, was found for all species overall and within most age groups stratifications, except for hookworm infection in preschool-aged children.

Conclusions/significance

This study demonstrates that, for certain demographic groups, a six-month gap between MDA in these communities is enough time for STH infection to return to STH prevalence levels recorded immediately before the previous MDA round, and that on average the same individuals are being consistently infected between MDA rounds.

Renal and Vascular Effects of Kallikrein Inhibition in a Model of <i>Lonomia obliqua</i> Venom-Induced Acute Kidney Injury

PLoS Neglected Tropical Diseases News - 14 February 2019 - 10:00pm

by Markus Berger, João Alfredo de Moraes, Walter Orlando Beys-da-Silva, Lucélia Santi, Paula Barros Terraciano, David Driemeier, Elizabeth Obino Cirne-Lima, Eduardo Pandolfi Passos, Maria Aparecida Ribeiro Vieira, Thereza Christina Barja-Fidalgo, Jorge Almeida Guimarães

Background

Lonomia obliqua venom is nephrotoxic and acute kidney injury (AKI) is the main cause of death among envenomed victims. Mechanism underlying L. obliqua-induced AKI involves renal hypoperfusion, inflammation, tubular necrosis and loss of glomerular filtration and tubular reabsorption capacities. In the present study, we aimed to investigate the contribution of kallikrein to the hemodynamic instability, inflammation and consequent renal and vascular impairment

Methodology/Principal findings

Addition of L. obliqua venom to purified prekallikrein and human plasma in vitro or to vascular smooth muscle cells (VSMC) in culture, was able to generate kallikrein in a dose-dependent manner. Injected in rats, the venom induced AKI and increased kallikrein levels in plasma and kidney. Kallikrein inhibition by aprotinin prevented glomerular injury and the decrease in glomerular filtration rate, restoring fluid and electrolyte homeostasis. The mechanism underlying these effects was associated to lowering renal inflammation, with decrease in pro-inflammatory cytokines and matrix metalloproteinase expression, reduced tubular degeneration, and protection against oxidative stress. Supporting the key role of kallikrein, we demonstrated that aprotinin inhibited effects directly associated with vascular injury, such as the generation of intracellular reactive oxygen species (ROS) and migration of VSMC induced by L. obliqua venom or by diluted plasma obtained from envenomed rats. In addition, kallikrein inhibition also ameliorated venom-induced blood incoagulability and decreased kidney tissue factor expression

Conclusions/Significance

These data indicated that kallikrein and consequently kinin release have a key role in kidney injury and vascular remodeling. Thus, blocking kallikrein may be a therapeutic alternative to control the progression of venom-induced AKI and vascular disturbances.

Effect of <i>Schistosoma mansoni</i> infection and its treatment on antibody responses to measles catch-up immunisation in pre-school children: A randomised trial

PLoS Neglected Tropical Diseases News - 14 February 2019 - 10:00pm

by Robert Tweyongyere, Beatrice R. Nassanga, Allan Muhwezi, Matthew Odongo, Swaib A. Lule, Rebecca N. Nsubuga, Emily L. Webb, Stephen C. Cose, Alison M. Elliott

Background

Schistosoma infection is associated with immune modulation that can influence responses to non-schistosome antigens. Vaccine responses may be impaired in S. mansoni-infected individuals. We investigated effects of S. mansoni infection on responses to childhood measles catch-up immunisation and of praziquantel treatment on this outcome in a randomised trial.

Methodology

The Immune Modulation and Childhood Immunisation (IMoChI) study was based in Entebbe, Uganda. Children aged 3–5 years (193 S. mansoni-infected and 61 uninfected) were enrolled. Infected children were randomised in a 1:1:1 ratio to receive praziquantel 2 weeks before, at time of, or 1 week after, measles catch-up immunisation. Plasma anti-measles IgG was measured at enrolment, 1 week and 24 weeks after measles immunisation. Primary outcomes were IgG levels and percentage of participants with levels considered protective against measles.

Results

Anti-measles IgG levels increased following immunisation, but at 1 week post-immunisation S. mansoni-infected, compared to uninfected, children had lower levels of anti-measles IgG (adjusted geometric mean ratio (aGMR) 0.4 [95% CI 0.2–0.7]) and the percentage with protective antibody levels was also lower (adjusted odds ratio 0.1 [0–0.9]). Among S. mansoni-infected children, anti-measles IgG one week post-immunisation was higher among those treated with praziquantel than among those who were not yet treated (treatment before immunisation, aGMR 2.3 [1.5–4.8]; treatment at immunisation aGMR 1.8 [1.1–3.5]). At 24 weeks post-immunisation, IgG levels did not differ between the trial groups, but tended to be lower among previously-infected children who were still S mansoni stool-positive than among those who became stool-negative.

Conclusions and significance

Our findings suggest that S. mansoni infection among pre-school children is associated with a reduced antibody response to catch-up measles immunisation, and that praziquantel treatment improves the response. S. mansoni infection may contribute to impaired vaccine responses in endemic populations; effective schistosomiasis control may be beneficial for vaccine efficacy. This should be further explored.

Trial registration

ISRCTN87107592.

A chronic bioluminescent model of experimental visceral leishmaniasis for accelerating drug discovery

PLoS Neglected Tropical Diseases News - 14 February 2019 - 10:00pm

by Raquel Álvarez-Velilla, Maria del Camino Gutiérrez-Corbo, Carmen Punzón, Maria Yolanda Pérez-Pertejo, Rafael Balaña-Fouce, Manuel Fresno, Rosa María Reguera

Background

Visceral leishmaniasis is a neglected parasitic disease with no vaccine available and its pharmacological treatment is reduced to a limited number of unsafe drugs. The scarce readiness of new antileishmanial drugs is even more alarming when relapses appear or the occurrence of hard-to-treat resistant strains is detected. In addition, there is a gap between the initial and late stages of drug development, which greatly delays the selection of leads for subsequent studies.

Methodology/Principal findings

In order to address these issues, we have generated a red-shifted luminescent Leishmania infantum strain that enables long-term monitoring of parasite burden in individual animals with an in vivo limit of detection of 106 intracellular amastigotes 48 h postinfection. For this purpose, we have injected intravenously different infective doses (104—5x108) of metacyclic parasites in susceptible mouse models and the disease was monitored from initial times to 21 weeks postinfection. The emission of light from the target organs demonstrated the sequential parasite colonization of liver, spleen and bone marrow. When miltefosine was used as proof-of-concept, spleen weight parasite burden and bioluminescence values decreased significantly.

Conclusions

In vivo bioimaging using a red-shifted modified Leishmania infantum strain allows the appraisal of acute and chronic stage of infection, being a powerful tool for accelerating drug development against visceral leishmaniasis during both stages and helping to bridge the gap between early discovery process and subsequent drug development.

The complexities and challenges of preventing and treating nontuberculous mycobacterial diseases

PLoS Neglected Tropical Diseases News - 14 February 2019 - 10:00pm

by Susan L. Baldwin, Sasha E. Larsen, Diane Ordway, Gail Cassell, Rhea N. Coler

Seemingly innocuous nontuberculous mycobacteria (NTM) species, classified by their slow or rapid growth rates, can cause a wide range of illnesses, from skin ulceration to severe pulmonary and disseminated disease. Despite their worldwide prevalence and significant disease burden, NTM do not garner the same financial or research focus as Mycobacterium tuberculosis. In this review, we outline the most abundant of over 170 NTM species and inadequacies of diagnostics and treatments and weigh the advantages and disadvantages of currently available in vivo animal models of NTM. In order to effectively combat this group of mycobacteria, more research focused on appropriate animal models of infection, screening of chemotherapeutic compounds, and development of anti-NTM vaccines and diagnostics is urgently needed.

Potential public health benefits from cat eradications on islands

PLoS Neglected Tropical Diseases News - 14 February 2019 - 10:00pm

by Luz A. de Wit, Donald A. Croll, Bernie Tershy, Maria Dolores Correa, Hector Luna-Pasten, Paulo Quadri, A. Marm Kilpatrick

Cats (Felis catus) are reservoirs of several pathogens that affect humans, including Toxoplasma gondii. Infection of pregnant women with T. gondii can cause ocular and neurological lesions in newborns, and congenital toxoplasmosis has been associated with schizophrenia, epilepsy, movement disorders, and Alzheimer’s disease. We compared seroprevalence of T. gondii and risk factors in people on seven islands in Mexico with and without introduced cats to determine the effect of cat eradication and cat density on exposure to T. gondii. Seroprevalence was zero on an island that never had cats and 1.8% on an island where cats were eradicated in 2000. Seroprevalence was significantly higher (12–26%) on the five islands with cats, yet it did not increase across a five-fold range of cat density. Having cats near households, being male and spending time on the mainland were significant risk factors for T. gondii seroprevalence among individuals, whereas eating shellfish was protective. Our results suggest that cats are an important source of T. gondii on islands, and eradicating, but not controlling, introduced cats from islands could benefit human health.

Potential of <i>Aedes albopictus</i> to cause the emergence of arboviruses in Morocco

PLoS Neglected Tropical Diseases News - 14 February 2019 - 10:00pm

by Fadila Amraoui, Wiem Ben Ayed, Yoann Madec, Chafika Faraj, Oumnia Himmi, Ameur Btissam, Mhammed Sarih, Anna-Bella Failloux

In 2015, the mosquito Aedes albopictus was detected in Rabat, Morocco. This invasive species can be involved in the transmission of more than 25 arboviruses. It is known that each combination of mosquito population and virus genotype leads to a specific interaction that can shape the outcome of infection. Testing the vector competence of local mosquitoes is therefore a prerequisite to assess the risks of emergence. A field-collected strain of Ae. albopictus from Morocco was experimentally infected with dengue (DENV), chikungunya (CHIKV), zika (ZIKV) and yellow fever (YFV) viruses. We found that this species can highly transmit CHIKV and to a lesser extent, DENV, ZIKV and YFV. Viruses can be detected in mosquito saliva at day 3 (CHIKV), day 14 (DENV and YFV), and day 21 (ZIKV) post-infection. These results suggest that the local transmission of these four arboviruses by Ae. albopictus newly introduced in Morocco is a likely scenario. Trial registration: ClinicalTrials.gov APAFIS#6573-201606l412077987v2.

A simple score to predict severe leptospirosis

PLoS Neglected Tropical Diseases News - 13 February 2019 - 10:00pm

by Simon Smith, Brendan J. Kennedy, Alexis Dermedgoglou, Suzanne S. Poulgrain, Matthew P. Paavola, Tarryn L. Minto, Michael Luc, Yu-Hsuan Liu, Josh Hanson

Background

The case-fatality rate of severe leptospirosis can exceed 50%. While prompt supportive care can improve survival, predicting those at risk of developing severe disease is challenging, particularly in settings with limited diagnostic support.

Methodology/Principal findings

We retrospectively identified all adults with laboratory-confirmed leptospirosis in Far North Queensland, Australia, between January 1998 and May 2016. Clinical, laboratory and radiological findings at presentation were correlated with the patients’ subsequent clinical course. Medical records were available in 402 patients; 50 (12%) had severe disease. The presence of oliguria (urine output ≤500 mL/24 hours, odds ratio (OR): 16.4, 95% confidence interval (CI): 6.9–38.8, p<0.001), abnormal auscultatory findings on respiratory examination (OR 11.2 (95% CI: 4.7–26.5, p<0.001) and hypotension (systolic blood pressure ≤100 mmHg, OR 4.3 (95% CI 1.7–10.7, p = 0.002) at presentation independently predicted severe disease. A three-point score (the SPiRO score) was devised using these three clinical variables, with one point awarded for each. A score could be calculated in 392 (98%) patients; the likelihood of severe disease rose incrementally: 8/287 (3%), 14/70 (20%), 18/26 (69%) and 9/9 (100%) for a score of 0, 1, 2 and 3 respectively (p = 0.0001). A SPiRO score <1 had a negative predictive value for severe disease of 97% (95% CI: 95–99%).

Conclusions/Significance

A simple, three-point clinical score can help clinicians rapidly identify patients at risk of developing severe leptospirosis, prompting early transfer to referral centres for advanced supportive care. This inexpensive, bedside assessment requires minimal training and may have significant utility in the resource-limited settings which bear the greatest burden of disease.

Maternal <i>Leishmania infantum</i> infection status has significant impact on leishmaniasis in offspring

PLoS Neglected Tropical Diseases News - 13 February 2019 - 10:00pm

by Angela J. Toepp, Carolyne Bennett, Benjamin Scott, Reid Senesac, Jacob J. Oleson, Christine A. Petersen

Visceral Leishmaniasis is a deadly disease caused by Leishmania infantum, endemic in more than 98 countries across the globe. Although the most common means of transmission is via a sand fly vector, there is growing evidence that vertical transmission may be critical for maintaining L. infantum infection within the reservoir, canine, population. Vertical transmission is also an important cause of infant morbidity and mortality particularly in sub-Saharan Africa. While vertical transmission of visceralizing species of Leishmania has been reported around the globe, risk factors associated with this unique means of Leishmania transmission have not been identified therefore interventions regarding this means of transmission have been virtually non-existent. Furthermore, the basic reproductive number, (R0), or number of new L. infantum infections that one infected mother or dam can cause has not been established for vertical transmission, also hampering the ability to assess the impact of this means of transmission within reservoir of human hosts. Canine Leishmaniosis (CanL) is enzootic within a U.S. hunting dog population. CanL is transmitted within this population via transplacental transmission with no reported vector transmission, despite many repeated attempts to find infected sand flies associated with these dogs and kennels. This population with predominantly, if not solely, vertical transmission of L. infantum was used to evaluate the critical risk factors for vertical transmission of Leishmania and establish the R0 of vertical L. infantum infection. Evaluation of 124 animals born to eighteen dams diagnostically positive for infection with L. infantum showed that there was a 13.84x greater chance of being positive for L. infantum within their lifetime if the mother was also positive within her lifetime (RR: 13.84, 95% CI: 3.54–54.20, p-value: <0.0001). The basic reproductive number for vertically transmitted L. infantum within this cohort was 4.12. These results underscore that there is a high risk of L. infantum infection to transmit from mother to offspring. Targeted public health interventions and control efforts that address vertical transmission of L. infantum are necessary in endemic countries to eliminate visceral leishmaniasis.

Potential for sylvatic and urban <i>Aedes</i> mosquitoes from Senegal to transmit the new emerging dengue serotypes 1, 3 and 4 in West Africa

PLoS Neglected Tropical Diseases News - 13 February 2019 - 10:00pm

by Alioune Gaye, Eryu Wang, Nikos Vasilakis, Hilda Guzman, Diawo Diallo, Cheikh Talla, Yamar Ba, Ibrahima Dia, Scott C. Weaver, Mawlouth Diallo

Dengue fever (DEN) is the most common arboviral disease in the world and dengue virus (DENV) causes 390 million annual infections around the world, of which 240 million are inapparent and 96 million are symptomatic. During the past decade a changing epidemiological pattern has been observed in Africa, with DEN outbreaks reported in all regions. In Senegal, all DENV serotypes have been reported. These important changes in the epidemiological profile of DEN are occurring in a context where there is no qualified vaccine against DEN. Further there is significant gap of knowledge on the vector bionomics and transmission dynamics in the African region to effectively prevent and control epidemics. Except for DENV-2, few studies have been performed with serotypes 1, 3, and 4, so this study was undertaken to fill out this gap. We assessed the vector competence of Aedes (Diceromyia) furcifer, Ae. (Diceromyia) taylori, Ae. (Stegomyia) luteocephalus, sylvatic and urban Ae. (Stegomyia) aegypti populations from Senegal for DENV-1, DENV-3 and DENV-4 using experimental oral infection. Whole bodies and wings/legs were tested for DENV presence by cell culture assays and saliva samples were tested by real time RT-PCR to estimate infection, disseminated infection and transmission rates. Our results revealed a low capacity of sylvatic and urban Aedes mosquitoes from Senegal to transmit DENV-1, DENV-3 and DENV-4 and an impact of infection on their mortality. The highest potential transmission rate was 20% despite the high susceptibility and disseminated infection rates up to 93.7% for the 3 Ae. aegypti populations tested, and 84.6% for the sylvatic vectors Ae. furcifer, Ae. taylori and Ae. luteocephalus.

Feasibility of feeding <i>Aedes aegypti</i> mosquitoes on dengue virus-infected human volunteers for vector competence studies in Iquitos, Peru

PLoS Neglected Tropical Diseases News - 12 February 2019 - 10:00pm

by Kanya C. Long, Juan Sulca, Isabel Bazan, Helvio Astete, Hugo L. Jaba, Crystyan Siles, Claudine Kocher, Stalin Vilcarromero, Julia Schwarz, Karin S. Escobedo-Vargas, Fanny Castro-Llanos, Leslye Angulo, Guadalupe Flores, Cesar Ramal-Asayag, Eric S. Halsey, Robert D. Hontz, Valerie A. Paz-Soldan, Thomas W. Scott, Louis Lambrechts, Amy C. Morrison

Background

Transmission of dengue virus (DENV) from humans to mosquitoes represents a critical component of dengue epidemiology. Examinations of this process have generally been hampered by a lack of methods that adequately represent natural acquisition of DENV by mosquitoes from humans. In this study, we assessed artificial and natural blood feeding methods based on rates of DENV infection and dissemination within mosquitoes for use in a field-based epidemiological cohort study in Iquitos, Peru.

Methodology/Principal findings

Our study was implemented, stepwise, between 2011 and 2015. Participants who were 5 years and older with 5 or fewer days of fever were enrolled from ongoing clinic- and neighborhood-based studies on dengue in Iquitos. Wild type, laboratory-reared Aedes aegypti were fed directly on febrile individuals or on blood collected from participants that was either untreated or treated with EDTA. Mosquitoes were tested after approximately 14 days of extrinsic incubation for DENV infection and dissemination. A total of 58 participants, with viremias ranging from 1.3 × 102 to 2.9 × 106 focus-forming units per mL of serum, participated in one or more feeding methods. DENV infection and dissemination rates were not significantly different following direct and indirect-EDTA feeding; however, they were significantly lower for mosquitoes that fed indirectly on blood with no additive. Relative to direct feeding, infection rates showed greater variation following indirect-EDTA than indirect-no additive feeding. Dissemination rates were correlated across all feeding methods. No differences were detected in DENV infection or dissemination rates in mosquitoes fed directly on participants with different dengue illness severity.

Conclusions/Significance

Our study demonstrates the feasibility of using direct and indirect feeding methods for field-based studies on vector competence. Direct mosquito feeding is preferable in terms of logistical ease, biosecurity, and reliability.

Vector competence of biting midges and mosquitoes for Shuni virus

PLoS Neglected Tropical Diseases News - 12 February 2019 - 10:00pm

by Tim W. R. Möhlmann, Judith Oymans, Paul J. Wichgers Schreur, Constantianus J. M. Koenraadt, Jeroen Kortekaas, Chantal B. F. Vogels

Background

Shuni virus (SHUV) is an orthobunyavirus that belongs to the Simbu serogroup. SHUV was isolated from diverse species of domesticated animals and wildlife, and is associated with neurological disease, abortions, and congenital malformations. Recently, SHUV caused outbreaks among ruminants in Israel, representing the first incursions outside the African continent. The isolation of SHUV from a febrile child in Nigeria and seroprevalence among veterinarians in South Africa suggests that the virus may have zoonotic potential as well. The high pathogenicity, extremely broad tropism, potential transmission via both biting midges and mosquitoes, and zoonotic features of SHUV require further investigation. This is important to accurately determine the risk for animal and human health, and to facilitate preparations for potential epidemics. To gain first insight into the potential involvement of biting midges and mosquitoes in SHUV transmission we have investigated the ability of SHUV to infect two species of laboratory-colonised biting midges and two species of mosquitoes.

Methodology/Principal findings

Culicoides nubeculosus, C. sonorensis, Culex pipiens pipiens, and Aedes aegypti were orally exposed to SHUV by providing an infectious blood meal. Biting midges showed high infection rates of approximately 40%-60%, whereas infection rates of mosquitoes were only 0–2%. Moreover, successful dissemination in both species of biting midges and no evidence for transmission by orally exposed mosquitoes was found.

Conclusions/Significance

The results of this study suggest that different species of Culicoides midges are efficient in SHUV transmission, while the involvement of mosquitoes has not been supported.

Genetic evidence of <i>Coxiella burnetii</i> infection in acute febrile illnesses in Iran

PLoS Neglected Tropical Diseases News - 11 February 2019 - 10:00pm

by Saber Esmaeili, Ashraf Mohabati Mobarez, Mohammad Khalili, Ehsan Mostafavi, Pardis Moradnejad

Mounting evidence suggests that Q-fever is more prevalent in Iran than originally believed. However, in most parts of the country, clinicians do not pay enough attention to Q fever in their differential diagnosis. The aim of this study was to investigate the prevalence of Coxiella burnetii in suspected cases of acute Q fever in north-western Iran using molecular techniques. Febrile patients were enrolled in the study and investigated for C. burnetii infection. Sera samples were tested using real-time PCR for detection of IS1111 gene, and positive samples were confirmed with nested PCR. Nine patients (4.2%) out of 216 suspected cases were positive for C. burnetii. Weakness and fatigue, headache, and lethargy were the most prevalent clinical symptoms in acute Q fever patients. According to the results of this study and other reports of human cases in Iran, the diagnosis system of Q fever in Iran should be urgently revamped.

Effect of a sanitation intervention on soil-transmitted helminth prevalence and concentration in household soil: A cluster-randomized controlled trial and risk factor analysis

PLoS Neglected Tropical Diseases News - 11 February 2019 - 10:00pm

by Lauren Steinbaum, John Mboya, Ryan Mahoney, Sammy M. Njenga, Clair Null, Amy J. Pickering

Improved sanitation has been associated with a reduced prevalence of soil-transmitted helminth (STH) infection and has been hypothesized to prevent fecal contamination from spreading throughout the household environment. We evaluated the effect of providing households with a pit latrine with a plastic slab and drophole cover, child feces management tools, and associated behavioral messaging on reducing STH eggs in household soil. We collected soil samples from 2107 households (898 control and 1209 improved sanitation intervention households) that were enrolled in the WASH Benefits cluster randomized controlled trial in rural Kenya and performed a post-intervention analysis after two years of intervention exposure. Following a pre-specified analysis plan, we combined all households that received the sanitation intervention into one group for comparison to control households. The prevalence of STH eggs in soil was 18.9% in control households and 17.0% in intervention households. The unadjusted prevalence ratio of total STH eggs in the intervention groups compared to the control group was 0.94 (95% CI: 0.78–1.13). The geometric mean concentration was 0.05 eggs/g dry soil in control households and intervention households. Unadjusted and adjusted models gave similar results. We found use of a shared latrine, presence of a roof over the sampling area, and the number of dogs owned at baseline was associated with an increased prevalence of STH eggs in soil; the presence of a latrine that was at least 2 years old and a latrine with a covered drophole was associated with a reduction in the prevalence of STH eggs in soil. Soil moisture content was also associated with an increased prevalence of STH eggs in soil. Our results indicate that an intervention designed to increase access to improved latrines and child feces management tools may not be enough to impact environmental occurrence of STH in endemic areas where latrine coverage is already high.

The safety and efficacy of miltefosine in the long-term treatment of post-kala-azar dermal leishmaniasis in South Asia – A review and meta-analysis

PLoS Neglected Tropical Diseases News - 11 February 2019 - 10:00pm

by Joyce Pijpers, Margriet L. den Boer, Dirk R. Essink, Koert Ritmeijer

Background

Miltefosine (MF) is the only oral drug available for treatment of visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). Although the drug is effective and well tolerated in treatment of VL, the efficacy and safety of MF for longer treatment durations (>28 days) in PKDL remains unclear. This study provides an overview of the current knowledge about safety and efficacy of long treatment courses with MF in PKDL, as a strategy in the VL elimination in South Asia.

Methodology/Principal findings

Literature was searched systematically for articles investigating MF treatment in PKDL. A meta-analysis included eight studies (total 324 PKDL patients) to estimate the efficacy of MF in longer treatment regimens (range 6–16 weeks). We found a per-protocol (PP) initial cure rate of 95.2% (95%CI 89.6–100.8) and a PP definite cure rate of 90% (95%CI 81.6–96.3). Descriptive analysis showed that 20% of patients experienced adverse events, which mostly had an onset in the first week of treatment and were likely to get more severe after four weeks of treatment. Gastrointestinal (GI) side effects such as vomiting, nausea, diarrhoea, and abdominal pain were most common.

Conclusions/Significance

Longer treatment regimens with MF are effective in PKDL patients in India, however with the caveat that the efficacy has recently been observed to decline. GI side effects are frequent, although mostly mild or moderate. However, on the basis of limited data, we cannot conclude that longer MF treatment regimens are safe. Moreover, VL and PKDL pharmacovigilance studies indicate a risk for serious adverse events, questioning the safety of MF. The provision of safer treatment regimens for PKDL patients are therefore recommended. Until these regimens are identified, it should be considered to halt the use of MF monotherapy for PKDL in order to preserve the drug’s efficacy.

Acceptability of <i>Aedes aegypti</i> blood feeding on dengue virus-infected human volunteers for vector competence studies in Iquitos, Peru

PLoS Neglected Tropical Diseases News - 11 February 2019 - 10:00pm

by Amy C. Morrison, Julia Schwarz, Kanya C. Long, Jhonny Cordova, Jennifer E. Rios, W. Lorena Quiroz, S. Alfonso Vizcarra, Robert D. Hontz, Thomas W. Scott, Louis Lambrechts, Valerie A. Paz Soldan

As part of a study to investigate drivers of dengue virus (DENV) transmission dynamics, this qualitative study explored whether DENV-infected residents of Iquitos, Peru, considered it acceptable (1) to participate in direct mosquito feeding experiments (lab-reared Aedes aegypti mosquitoes fed directly on human volunteers) and (2) to provide blood meals indirectly (Ae. aegypti fed on blood drawn from participants by venipuncture). Twelve focus group discussions (FGDs; 94 participants: 82 females and 12 males) were conducted in January 2014 to explore six themes: (1) concerns and preferences regarding direct mosquito feeds and blood draws, (2) comprehension of and misconceptions about study procedures, (3) motivating factors for participation, (4) acceptability of children’s participation, (5) willingness to provide multiple samples over several days, and (6) preference for direct feedings in homes versus the study laboratory. Results of FGDs, including one with 5 of 53 past direct mosquito feed participants, indicated that mosquito feeding procedures are acceptable to Iquitos residents when they are provided with information and a few key messages are properly reinforced. FGD participants’ concerns focused primarily on safety issues rather than discomfort associated with mosquito bites. A video explaining the study dramatically increased comprehension of the study procedures. The majority of participants expressed a preference for mosquito feeding over venipuncture. Adults supported child participation if the children themselves assented. For most participants, home feedings were preferred over those in a laboratory. A major impetus for participation was the idea that results would contribute to an improved understanding of DENV transmission in Iquitos. Findings from our study will support future large-scale studies that employ direct mosquito feeding, a low-risk, non-invasive procedure that is experimentally superior to artificial mosquito feeding methods.

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