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1.
  • Abate, Ebba, et al. (author)
  • Asymptomatic Helminth Infection in Active Tuberculosis Is Associated with Increased Regulatory and Th-2 Responses and a Lower Sputum Smear Positivity
  • 2015
  • In: PLoS Neglected Tropical Diseases. - : PUBLIC LIBRARY SCIENCE. - 1935-2727 .- 1935-2735. ; 9:8
  • Journal article (peer-reviewed)abstract
    • Background The impact of intestinal helminth infection on the clinical presentation and immune response during active tuberculosis (TB) infection is not well characterized. Our aim was to investigate whether asymptomatic intestinal helminth infection alters the clinical signs and symptoms as well as the cell mediated immune responses in patients with active TB.Methodology Consecutive, newly diagnosed TB patients and healthy community controls (CCs) were recruited in North-west Ethiopia. TB-score, body mass index and stool samples were analyzed. Cells from HIV-negative TB patients (HIV-/TB) and from CCs were analyzed for regulatory T-cells (Tregs) and cytokine responses using flow cytometry and ELISPOT, respectively.Results A significantly higher ratio of helminth co-infection was observed in TB patients without HIV (Helm+/HIV-/TB) compared to HIV negative CCs, (40% (121/306) versus 28% (85/306), p = 0.003). Helm+/HIV-/TB patients showed significantly increased IL-5 secreting cells compared to Helm-/HIV-/TB (37 SFU (IQR:13-103) versus 2 SFU (1-50); p = 0.02, n = 30). Likewise, levels of absolute Tregs (9.4 (3.2-16.7) cells/mu l versus 2.4 (1.1-4.0) cells/mu l; p = 0.041) and IL-10 secreting cells (65 SFU (7-196) versus 1 SFU (0-31); p = 0.014) were significantly higher in Helm+/HIV-/TB patients compared to Helm-/HIV-/TB patients. In a multivariate analysis, a lower rate of sputum smear positivity for acid fast bacilli, lower body temperature, and eosinophilia were independently associated with helminth infection in TB patients.Conclusions Asymptomatic helminth infection is associated with increased regulatory T-cell and Th2-type responses and a lower rate of sputum smear positivity. Further studies are warranted to investigate the clinical and immunological impact of helminth infection in TB patients.
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2.
  • Abioye, Ajibola I., et al. (author)
  • Maternal, placental and cord blood cytokines and the risk of adverse birth outcomes among pregnant women infected with Schistosoma japonicum in the Philippines
  • 2019
  • In: PLoS Neglected Tropical Diseases. - : PUBLIC LIBRARY SCIENCE. - 1935-2727 .- 1935-2735. ; 13:6
  • Journal article (peer-reviewed)abstract
    • Background The objectives of this study were to 1) evaluate the influence of treatment with praziquantel on the inflammatory milieu in maternal, placental, and cord blood, 2) assess the extent to which proinflammatory signatures in placental and cord blood impacts birth outcomes, and 3) evaluate the impact of other helminths on the inflammatory micro environment. Methods/Findings This was a secondary analysis of samples from 369 mother-infant pairs participating in a randomized controlled trial of praziquantel given at 12-16 weeks gestation. We performed regression analysis to address our study objectives. In maternal peripheral blood, the concentrations of CXCL8, and TNF receptor I and II decreased from 12 to 32 weeks gestation, while IL-13 increased. Praziquantel treatment did not significantly alter the trajectory of the concentration of any of the cytokines examined. Hookworm infection was associated with elevated placental IL-1, CXCL8 and IFN-gamma. The risk of small-for-gestational age increased with elevated IL-6, IL-10, and CXCL8 in cord blood. The risk of prematurity was increased when cord blood sTNFRI and placental IL-5 were elevated. Conclusions Our study suggests that fetal cytokines, which may be related to infectious disease exposures, contribute to poor intrauterine growth. Additionally, hookworm infection influences cytokine concentrations at the maternal-fetal interface. Clinical Trial Registry number and website ClinicalTrials.gov (NCT00486863). Author summary Schistosomiasis is one of the most prevalent parasitic tropical diseases, and it is primarily treated with the drug praziquantel. This study examined the effects of praziquantel treatment for schistosomiasis and the presence of geohelminth infections during pregnancy on cytokines in maternal, placental, and cord blood, and examined the effects of pro-inflammatory signatures at the maternal-fetal interface on perinatal outcomes. We analyzed the data of 369 mother-infant pairs obtained from a randomized controlled trial of praziquantel given at 12-16 weeks gestation. Praziquantel treatment did not significantly alter the trajectory of the concentration of any of the cytokines examined. Elevated levels of both Th1 and Th2 cytokines were associated with the risk of adverse perinatal outcomes (small-for-gestational age and prematurity). Hookworm coinfection at 12 weeks gestation was, however, related to elevated levels of certain cytokines in the placenta (IL-1, IL-5, CXCL8 and IFN-gamma).
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3.
  • Affognon, Hippolyte, et al. (author)
  • Ethnic groups' knowledge, attitude and practices and Rift Valley fever exposure in Isiolo County of Kenya
  • 2017
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 11:3
  • Journal article (peer-reviewed)abstract
    • Rift Valley fever (RVF) is an emerging mosquito-borne viral hemorrhagic fever in Africa and the Arabian Peninsula, affecting humans and livestock. For spread of infectious diseases, including RVF, knowledge, attitude and practices play an important role, and the understanding of the influence of behavior is crucial to improve prevention and control efforts. The objective of the study was to assess RVF exposure, in a multiethnic region in Kenya known to experience RVF outbreaks, from the behavior perspective. We investigated how communities in Isiolo County, Kenya were affected, in relation to their knowledge, attitude and practices, by the RVF outbreak of 2006/2007. A cross-sectional study was conducted involving 698 households selected randomly from three different ethnic communities. Data were collected using a structured questionnaire regarding knowledge, attitudes and practices that could affect the spread of RVF. In addition, information was collected from the communities regarding the number of humans and livestock affected during the RVF outbreak. This study found that better knowledge about a specific disease does not always translate to better practices to avoid exposure to the disease. However, the high knowledge, attitude and practice score measured as a single index of the Maasai community may explain why they were less affected, compared to other investigated communities (Borana and Turkana), by RVF during the 2006/2007 outbreak. We conclude that RVF exposure in Isiolo County, Kenya during the outbreak was likely determined by the behavioral differences of different resident community groups. We then recommend that strategies to combat RVF should take into consideration behavioral differences among communities.
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4.
  • Aira, Naomi, et al. (author)
  • Species dependent impact of helminth-derived antigens on human macrophages infected with Mycobacterium tuberculosis: Direct effect on the innate anti-mycobacterial response
  • 2017
  • In: PLoS Neglected Tropical Diseases. - : PUBLIC LIBRARY SCIENCE. - 1935-2727 .- 1935-2735. ; 11:3
  • Journal article (peer-reviewed)abstract
    • Background In countries with a high prevalence of tuberculosis there is high coincident of helminth infections that might worsen disease outcome. While Mycobacterium tuberculosis (Mtb) gives rise to a pro-inflammatory Th1 response, a Th2 response is typical of helminth infections. A strong Th2 response has been associated with decreased protection against tuberculosis. Principal findings We investigated the direct effect of helminth-derived antigens on human macrophages, hypothesizing that helminths would render macrophages less capable of controlling Mtb. Measuring cytokine output, macrophage surface markers with flow cytometry, and assessing bacterial replication and phagosomal maturation revealed that antigens from different species of helminth directly affect macrophage responses to Mtb. Antigens from the tapeworm Hymenolepis diminuta and the nematode Trichuris muris caused an anti-inflammatory response with M2-type polarization, reduced macrophage phagosome maturation and ability to activate T cells, along with increased Mtb burden, especially in T. muris exposed cells which also induced the highest IL-10 production upon co-infection. However, antigens from the trematode Schistosoma mansoni had the opposite effect causing a decrease in IL-10 production, M1-type polarization and increased control of Mtb. Conclusion We conclude that, independent of any adaptive immune response, infection with helminth parasites, in a species-specific manner can influence the outcome of tuberculosis by either enhancing or diminishing the bactericidal function of macrophages.
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5.
  • Alam, M., et al. (author)
  • Antigen-Specific Memory B-cell Responses to Enterotoxigenic Escherichia coli Infection in Bangladeshi Adults
  • 2014
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 8:4
  • Journal article (peer-reviewed)abstract
    • Background: Multiple infections with diverse enterotoxigenic E. coli (ETEC) strains lead to broad spectrum protection against ETEC diarrhea. However, the precise mechanism of protection against ETEC infection is still unknown. Therefore, memory B cell responses and affinity maturation of antibodies to the specific ETEC antigens might be important to understand the mechanism of protection. Methodology: In this study, we investigated the heat labile toxin B subunit (LTB) and colonization factor antigens (CFA/I and CS6) specific IgA and IgG memory B cell responses in Bangladeshi adults (n = 52) who were infected with ETEC. We also investigated the avidity of IgA and IgG antibodies that developed after infection to these antigens. Principal Findings: Patients infected with ETEC expressing LT or LT+heat stable toxin (ST) and CFA/I group or CS6 colonization factors developed LTB, CFA/I or CS6 specific memory B cell responses at day 30 after infection. Similarly, these patients developed high avidity IgA and IgG antibodies to LTB, CFA/I or CS6 at day 7 that remained significantly elevated at day 30 when compared to the avidity of these specific antibodies at the acute stage of infection (day 2). The memory B cell responses, antibody avidity and other immune responses to CFA/I not only developed in patients infected with ETEC expressing CFA/I but also in those infected with ETEC expressing CFA/I cross-reacting epitopes. We also detected a significant positive correlation of LTB, CFA/I and CS6 specific memory B cell responses with the corresponding increase in antibody avidity. Conclusion: This study demonstrates that natural infection with ETEC induces memory B cells and high avidity antibodies to LTB and colonization factor CFA/I and CS6 antigens that could mediate anamnestic responses on re-exposure to ETEC and may help in understanding the requirements to design an effective vaccination strategies.
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6.
  • Alm, Erik, et al. (author)
  • Universal Single-Probe RT-PCR Assay for Diagnosis of Dengue Virus Infections
  • 2014
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 8:12, s. e3416-
  • Journal article (peer-reviewed)abstract
    • Background: Dengue is a mosquito-borne viral disease that has become more prevalent in the last few decades. Most patients are viremic when they present with symptoms, and early diagnosis of dengue is important in preventing severe clinical complications associated with this disease and also represents a key factor in differential diagnosis. Here, we designed and validated a hydrolysis-probe-based one-step real-time RT-PCR assay that targets the genomes of dengue virus serotypes 1-4. Methodology/Principal Findings: The primers and probe used in our RT-PCR assay were designed to target the 39 untranslated region of all complete genome sequences of dengue virus available in GenBank (n=3,305). Performance of the assay was evaluated using in vitro transcribed RNA, laboratory-adapted virus strains, external control panels, and clinical specimens. The linear dynamic range was found to be 10(4)-10(11) GCE/mL, and the detection limit was between 6.0x10(2) and 1.1x10(3) GCE/mL depending on target sequence. The assay did not cross-react with human RNA, nor did it produce false-positive results for other human pathogenic flaviviruses or clinically important etiological agents of febrile illnesses. We used clinical serum samples obtained from returning travelers with dengue-compatible symptomatology (n = 163) to evaluate the diagnostic relevance of our assay, and laboratory diagnosis performed by the RT-PCR assay had 100% positive agreement with diagnosis performed by NS1 antigen detection. In a retrospective evaluation including 60 archived serum samples collected from confirmed dengue cases 1-9 days after disease onset, the RT-PCR assay detected viral RNA up to 9 days after appearance of symptoms. Conclusions/Significance: The validation of the RT-PCR assay presented here indicates that this technique can be a reliable diagnostic tool, and hence we suggest that it be introduced as the method of choice during the first 5 days of dengue symptoms.
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7.
  • Ansell, Brendan R. E., et al. (author)
  • Time-Dependent Transcriptional Changes in Axenic Giardia duodenalis Trophozoites
  • 2015
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 9:12
  • Journal article (peer-reviewed)abstract
    • Giardia duodenalis is the most common gastrointestinal protozoan parasite of humans and a significant contributor to the global burden of both diarrheal disease and post-infectious chronic disorders. Although G. duodenalis can be cultured axenically, significant gaps exist in our understanding of the molecular biology and metabolism of this pathogen. The present study employed RNA sequencing to characterize the mRNA transcriptome of G. duodenalis trophozoites in axenic culture, at log (48 h of growth), stationary (60 h), and declining (96 h) growth phases. Using similar to 400-times coverage of the transcriptome, we identified 754 differentially transcribed genes (DTGs), mainly representing two large DTG groups: 438 that were down-regulated in the declining phase relative to log and stationary phases, and 281 that were up-regulated. Differential transcription of prominent antioxidant and glycolytic enzymes implicated oxygen tension as a key factor influencing the transcriptional program of axenic trophozoites. Systematic bioinformatic characterization of numerous DTGs encoding hypothetical proteins of unknown function was achieved using structural homology searching. This powerful approach greatly informed the differential transcription analysis and revealed putative novel antioxidant-coding genes, and the presence of a nearcomplete two-component-like signaling system that may link cytosolic redox or metabolite sensing to the observed transcriptional changes. Motif searching applied to promoter regions of the two large DTG groups identified different putative transcription factor-binding motifs that may underpin global transcriptional regulation. This study provides new insights into the drivers and potential mediators of transcriptional variation in axenic G. duodenalis and provides context for static transcriptional studies.
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8.
  • Bewket, Gezahegn, et al. (author)
  • Helminth species dependent effects on Th1 and Th17 cytokines in active tuberculosis patients and healthy community controls
  • 2022
  • In: PLoS Neglected Tropical Diseases. - : PUBLIC LIBRARY SCIENCE. - 1935-2727 .- 1935-2735. ; 16:8
  • Journal article (peer-reviewed)abstract
    • Despite that the impact of different helminth species is not well explored, the current dogma states that helminths affect the Th1/Th2 balance which in turn affects the risk of tuberculosis (TB) reactivation and severity of disease. We investigated the influence of helminth species on cytokine profiles including IL-17A in TB patients and healthy community controls (CCs). In total, 104 newly diagnosed pulmonary TB patients and 70 HIV negative and Quanti-FERON negative CCs in Gondar, Ethiopia were included following helminth screening by stool microscopy. Plasma samples and ex vivo stimulation of peripheral blood mononuclear cells (PBMCs) with purified protein derivative (PPD) and Staphylococcus enterotoxin B (SEB) was used to determine cytokine profiles by cytometric bead array. In CCs, Ascaris lumbricoides or Schistosoma mansoni infections were associated with an impaired Th1-type response (IFN-gamma, IL-6 and TNF-alpha) in PBMCs mainly with SEB stimulations, whereas in TB patients only hookworm infection showed a similar pattern. Among CCs, the IL-17A response in PBMCs stimulated with SEB was higher only for S. mansoni, whereas in TB patients, the elevated systemic IL-17A plasma level was significantly suppressed in hookworm infected TB patients compared to patients without helminth coinfection. Following treatment of TB and helminth infection there was a general decrease in ex vivio IL-10 and TNF-alpha production in unstimulated, PPD or SEB stimulated PBMCs that was the most pronounced and significant in TB patients infected with S. mansoni, whereas the follow-up levels of IFN-gamma and IL-17A was significantly increased only in TB patients without helminth coinfection from PBMCs stimulated mainly with SEB. In summary, in addition to confirming helminth specific effects on the Th1/Th2 response before and after TB treatment, our novel finding is that IL-17A was impaired in helminth infected TB patients especially for hookworm, indicating a helminth species-specific immunoregulatory effect on IL-17A which needs to be further investigated.
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9.
  • Bewket, Gezahegn, et al. (author)
  • Helminth species specific expansion and increased TNF-alpha production of non-classical monocytes during active tuberculosis
  • 2021
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science. - 1935-2727 .- 1935-2735. ; 15:3
  • Journal article (peer-reviewed)abstract
    • Author summary Monocytes are important cells for the early innate immune response and play an integral part during inflammation and infection. Classical monocytes, the dominant monocyte subset during homeostasis and health, have been linked to efficient TB protection. Intermediate or non-classical monocytes have instead been associated with uncontrolled inflammation (TNF-alpha), cell death, and poor protection against Mycobacterium tuberculosis. In areas endemic for intestinal helminths, the immunoregulatory effects of monocytes may affect development or progression of TB disease. The role of monocyte subsets during helminth/TB coinfection have not been studied. In Gondar, Ethiopia, we show that in patients with helminth infection, a helminth species dependent expansion of non-classical monocytes is triggered, where Ascaris and hookworm had the strongest effect in coinfected pulmonary TB-patients. The increase in non-classical monocytes was mainly detected in coinfected patients with a low-to-intermediate disease severity. Only coinfection with helminths and TB induced an increased TNF-alpha response in monocytes. Thus, we found a helminth species-specific dysregulation of monocyte subset distribution and functionality in coinfected TB-patients which could affect TB pathogenesis. Both Mycobacterium tuberculosis infection and helminths may affect innate immune mechanisms such as differential effects on monocytes towards the non-classical and intermediate subsets that favor bacterial persistence. Our aim, was to investigate helminth species specific effects on the frequency and functional activity of monocyte subsets in patients with active tuberculosis and healthy subjects. HIV-negative patients with active pulmonary tuberculosis (PTB) and community controls (CCs) in Gondar, Ethiopia were screened for helminth infection by stool microscopy. Flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and ex vivo stimulation with purified protein derivative (PPD) and helminth antigens were used to characterize the distribution of monocyte subsets and their function. A total of 74 PTB patients and 57 CCs with and without helminth infection were included. Non-classical monocytes were increased in PTB patients with Ascaris and hookworm infection but not in Schistosoma-infected patients. Ascaris had the strongest effect in increasing the frequency of non-classical monocytes in both PTB patients and CCs, whereas PTB without helminth infection did not affect the frequency of monocyte subsets. There was a helminth specific increase in the frequency of TNF-alpha producing non-classical monocytes in hookworm infected PTB patients, both with and without PPD-stimulation. Low-to-intermediate TB disease severity associated with increased frequency of non-classical monocytes only for helminth-positive PTB patients, and the frequency of TNF-alpha producing monocytes were significantly higher in intermediate and non-classical monocytes of helminth positive PTB patients with an intermediate disease score. Helminth infection affected the frequency of monocyte subsets and function both in TB patients and controls which was helminth species dependent in TB patients. The clinical role of this potential immunomodulatory effect needs further study and may affect the response and protection to tuberculosis in areas where helminth infections are endemic.
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10.
  • Bowman, Leigh, et al. (author)
  • A comparison of Zika and dengue outbreaks using national surveillance data in the Dominican Republic
  • 2018
  • In: PLoS Neglected Tropical Diseases. - : Public Library Science. - 1935-2727 .- 1935-2735. ; 12:11
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Aedes-borne arboviruses continue to precipitate epidemics worldwide. In Dominican Republic, the appearance of Zika virus cases that closely followed a large dengue epidemic provided an opportunity to study the different transmission drivers behind these two flaviviruses. Retrospective datasets were used to collect information on the populations at risk and descriptive statistics were used to describe the outbreaks on a national scale.METHODOLOGY/ PRINCIPAL FINDINGS: Expectedly, box plots showed that 75% of dengue was reported in those aged <20 years while Zika infections were more widely dispersed among the population. Dengue attack rates were marginally higher among males at 25.9 per 10,000 population vs. 21.5 per 10,000 population for females. Zika infections appeared to be highly clustered among females (73.8% (95% CI 72.6%, 75.0%; p<0.05)); age-adjusted Zika attack rates among females were 7.64 per 10,000 population compared with 2.72 per 10,000 population among males. R0 calculations stratified by sex also showed a significantly higher metric among females: 1.84 (1.82, 1.87; p<0.05) when compared to males at 1.72 (1.69, 1.75; p<0.05). However, GBS attack rates stratified by sex revealed slightly higher risk in males vs. females, at 0.62 and 0.57 per 10,000 population respectively.CONCLUSIONS/ SIGNIFICANCE: Evidence suggests little impact of existing dengue immunity on reported attack rates of Zika at the population level. Confounding of R0 and incident risk calculations by sex-specific over-reporting can alter the reliability of epidemiological metrics, which could be addressed using associated proxy syndromes or conditions to explore seemingly sex-skewed incidence. The findings indicate that community awareness campaigns, through influencing short-term health seeking behaviour, remain the most plausible mechanism behind increased reporting among women of reproductive age, although biological susceptibility cannot yet be ruled out. Media campaigns and screening are therefore recommended for women of reproductive age during Zika outbreaks. Future research should focus on clinical Zika outcomes among dengue seropositive individuals.
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11.
  • Bray, Daniel (author)
  • Multi-modal Analysis of Courtship Behaviour in the Old World Leishmaniasis Vector Phlebotomus argentipes
  • 2014
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 8
  • Journal article (peer-reviewed)abstract
    • Background: The sand fly Phlebotomus argentipes is arguably the most important vector of leishmaniasis worldwide. As there is no vaccine against the parasites that cause leishmaniasis, disease prevention focuses on control of the insect vector. Understanding reproductive behaviour will be essential to controlling populations of P. argentipes, and developing new strategies for reducing leishmaniasis transmission. Through statistical analysis of male-female interactions, this study provides a detailed description of P. argentipes courtship, and behaviours critical to mating success are highlighted. The potential for a role of cuticular hydrocarbons in P. argentipes courtship is also investigated, by comparing chemicals extracted from the surface of male and female flies.Principal Findings: P. argentipes courtship shared many similarities with that of both Phlebotomus papatasi and the New World leishmaniasis vector Lutzomyia longipalpis. Male wing-flapping while approaching the female during courtship predicted mating success, and touching between males and females was a common and frequent occurrence. Both sexes were able to reject a potential partner. Significant differences were found in the profile of chemicals extracted from the surface of males and females. Results of GC analysis indicate that female extracts contained a number of peaks with relatively short retention times not present in males. Extracts from males had higher peaks for chemicals with relatively long retention times.Conclusions: The importance of male approach flapping suggests that production of audio signals through wing beating, or dispersal of sex pheromones, are important to mating in this species. Frequent touching as a means of communication, and the differences in the chemical profiles extracted from males and females, may also indicate a role for cuticular hydrocarbons in P. argentipes courtship. Comparing characteristics of successful and unsuccessful mates could aid in identifying the modality of signals involved in P. argentipes courtship, and their potential for use in developing new strategies for vector control.
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12.
  • Burgert-Brucker, Clara R., et al. (author)
  • Risk factors associated with failing pre-transmission assessment surveys (pre-TAS) in lymphatic filariasis elimination programs : Results of a multi-country analysis
  • 2020
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 14:6
  • Journal article (peer-reviewed)abstract
    • Achieving elimination of lymphatic filariasis (LF) as a public health problem requires a minimum of five effective rounds of mass drug administration (MDA) and demonstrating low prevalence in subsequent assessments. The first assessments recommended by the World Health Organization (WHO) are sentinel and spot-check sites-referred to as pre-transmission assessment surveys (pre-TAS)-in each implementation unit after MDA. If pre-TAS shows that prevalence in each site has been lowered to less than 1% microfilaremia or less than 2% antigenemia, the implementation unit conducts a TAS to determine whether MDA can be stopped. Failure to pass pre-TAS means that further rounds of MDA are required. This study aims to understand factors influencing pre-TAS results using existing programmatic data from 554 implementation units, of which 74 (13%) failed, in 13 countries. Secondary data analysis was completed using existing data from Bangladesh, Benin, Burkina Faso, Cameroon, Ghana, Haiti, Indonesia, Mali, Nepal, Niger, Sierra Leone, Tanzania, and Uganda. Additional covariate data were obtained from spatial raster data sets. Bivariate analysis and multilinear regression were performed to establish potential relationships between variables and the pre-TAS result. Higher baseline prevalence and lower elevation were significant in the regression model. Variables statistically significantly associated with failure (p-value <= 0.05) in the bivariate analyses included baseline prevalence at or above 5% or 10%, use of Filariasis Test Strips (FTS), primary vector of Culex, treatment with diethylcarbamazine-albendazole, higher elevation, higher population density, higher enhanced vegetation index (EVI), higher annual rainfall, and 6 or more rounds of MDA. This paper reports for the first time factors associated with pre-TAS results from a multi-country analysis. This information can help countries more effectively forecast program activities, such as the potential need for more rounds of MDA, and prioritize resources to ensure adequate coverage of all persons in areas at highest risk of failing pre-TAS.
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13.
  • Capasso, Ariadna, et al. (author)
  • Incidence of Guillain-Barre Syndrome (GBS) in Latin America and the Caribbean before and during the 2015-2016 Zika virus epidemic : A systematic review and meta-analysis
  • 2019
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 13:8
  • Research review (peer-reviewed)abstract
    • Background: A severe neurological disorder, Guillain-Barré syndrome (GBS) is the leading cause of acute flaccid paralysis. Enhanced surveillance of GBS in Latin America and the Caribbean (LAC) following the 2015–2016 Zika virus (ZIKV) epidemic presents an opportunity to estimate, for the first time, the regional incidence of GBS.Methods and findings: For this systematic review and meta-analysis, we searched nine scientific databases and grey literature from January 1, 1980 to October 1, 2018. Sources with primary data on incident GBS cases in LAC within a well-defined population and timeframe, published in English, Spanish, Portuguese, or French, were included. We calculated the annual GBS incidence rates (IRs) and 95% confidence intervals (CIs) for each source based on published data. Following an assessment of heterogeneity, we used random-effects meta-analysis to calculate the pooled annual IR of GBS. The study is registered with PROSPERO, number CRD42018086659. Of the 6568 initial citation hits, 31 were eligible for inclusion. Background annual GBS IRs in Latin America ranged from 0.40 in Brazil to 2.12/100,000 in Chile. The pooled annual IR in the Caribbean was 1.64 (95% CI 1.29–2.12, I2<0.01, p = 0.44). During the ZIKV epidemic, GBS IRs ranged from 0.62 in Mexico to 9.35/100,000 in Martinique. GBS increased 2.6 (95% CI 2.3–2.9) times during ZIKV and 1.9 (95% CI 1.1–3.4) times during chikungunya outbreaks over background rates. A limitation of this review is that the studies included employed different methodologies to find and ascertain cases of GBS, which could contribute to IR heterogeneity. In addition, it is important to consider that data on GBS are lacking for many countries in the region.Conclusions: Background IRs of GBS appear to peak during arboviral disease outbreaks. The current review contributes to an understanding of the epidemiology of GBS in the LAC region, which can inform healthcare system planning and preparedness, particularly during arboviral epidemics.
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14.
  • Carrasco, David (author)
  • Trypanosomes Modify the Behavior of Their Insect Hosts: Effects on Locomotion and on the Expression of a Related Gene
  • 2015
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 9
  • Journal article (peer-reviewed)abstract
    • BackgroundAs a result of evolution, the biology of triatomines must have been significantly adapted to accommodate trypanosome infection in a complex network of vector-vertebrate-parasite interactions. Arthropod-borne parasites have probably developed mechanisms, largely still unknown, to exploit the vector-vertebrate host interactions to ensure their transmission to suitable hosts. Triatomines exhibit a strong negative phototaxis and nocturnal activity, believed to be important for insect survival against its predators.Methodology/Principal FindingsIn this study we quantified phototaxis and locomotion in starved fifth instar nymphs of Rhodnius prolixus infected with Trypanosoma cruzi or Trypanosoma rangeli. T. cruzi infection did not alter insect phototaxis, but induced an overall 20% decrease in the number of bug locomotory events. Furthermore, the significant differences induced by this parasite were concentrated at the beginning of the scotophase. Conversely, T. rangeli modified both behaviors, as it significantly decreased bug negative phototaxis, while it induced a 23% increase in the number of locomotory events in infected bugs. In this case, the significant effects were observed during the photophase. We also investigated the expression of Rpfor, the triatomine ortholog of the foraging gene known to modulate locomotion in other insects, and found a 4.8 fold increase for T. rangeli infected insects.Conclusions/SignificanceWe demonstrated for the first time that trypanosome infection modulates the locomotory activity of the invertebrate host. T. rangeli infection seems to be more broadly effective, as besides affecting the intensity of locomotion this parasite also diminished negative phototaxis and the expression of a behavior-associated gene in the triatomine vector.
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15.
  • de Glanville, William A., et al. (author)
  • Poor performance of the rapid test for human brucellosis in health facilities in Kenya
  • 2017
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 11:4
  • Journal article (peer-reviewed)abstract
    • Human brucellosis is considered to be an important but typically under-diagnosed cause of febrile illness in many low and middle-income countries. In Kenya, and throughout East Africa, laboratory diagnosis for the disease is based primarily on the febrile antigen Brucella agglutination test (FBAT), yet few studies of the diagnostic accuracy of this test exist. Assessment of the performance of the FBAT is essential for its appropriate clinical use, as well as for evaluating surveillance data reported by public health systems. To assess FBAT performance, we collected sera from people with symptoms compatible with brucellosis attending two health facilities in Busia County, Kenya. Sera were tested using the FBAT and results compared with those from the Rose Bengal Test (RBT), an assay with well-known performance characteristics. Positives on either test were confirmed using the classical serum agglutination test (SAT)-Coombs test combination and a rapid IgM/IgG lateral flow immunochromatography assay (LFA). A questionnaire focussing on known risk factors for exposure to Brucella spp. was also conducted, and relationships with FBAT positivity examined using logistic regression. Out of 825 recruited individuals, 162 (19.6%) were classified as positive using the FBAT. In contrast, only eight (1.0%) were positive using the RBT. Of the 162 FBAT positives, one (0.62%) had an atypical agglutination in SAT and three (1.9%) showed low Coombs titres. Out of 148 FBAT positive individuals tested using the LFA, five (3.4%) were IgM positive and none were IgG positive. Poor or no correlation was observed between FBAT results and most established risk factors for Brucella infection. We observed substantial disagreement between the FBAT and a number of well-known serological tests, with the majority of reactive FBAT results appearing to be false positives. Poor FBAT specificity, combined with a lack of confirmatory testing, strongly suggests overdiagnosis of brucellosis is common in this low prevalence setting. This is expected to have important economic impacts on affected patients subjected to the long and likely unnecessary courses of multiple antibiotics required for treatment of the disease.
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16.
  • DeRaedt Banks, Sarah, et al. (author)
  • Permethrin-Treated Clothing as Protection against the Dengue Vector, Aedes aegypti : Extent and Duration of Protection
  • 2015
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 9:10
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: Dengue transmission by the mosquito vector, Aedes aegypti, occurs indoors and outdoors during the day. Personal protection of individuals, particularly when outside, is challenging. Here we assess the efficacy and durability of different types of insecticide-treated clothing on laboratory-reared Ae. aegypti.METHODS: Standardised World Health Organisation Pesticide Evaluation Scheme (WHOPES) cone tests and arm-in-cage assays were used to assess knockdown (KD) and mortality of Ae. aegypti tested against factory-treated fabric, home-dipped fabric and microencapsulated fabric. Based on the testing of these three different treatment types, the most protective was selected for further analysis using arm-in cage assays with the effect of washing, ultra-violet light, and ironing investigated using high pressure liquid chromatography.RESULTS: Efficacy varied between the microencapsulated and factory dipped fabrics in cone testing. Factory-dipped clothing showed the greatest effect on KD (3 min 38.1%; 1 hour 96.5%) and mortality (97.1%) with no significant difference between this and the factory dipped school uniforms. Factory-dipped clothing was therefore selected for further testing. Factory dipped clothing provided 59% (95% CI = 49.2%- 66.9%) reduction in landing and a 100% reduction in biting in arm-in-cage tests. Washing duration and technique had a significant effect, with insecticidal longevity shown to be greater with machine washing (LW50 = 33.4) compared to simulated hand washing (LW50 = 17.6). Ironing significantly reduced permethrin content after 1 week of simulated use, with a 96.7% decrease after 3 months although UV exposure did not reduce permethrin content within clothing significantly after 3 months simulated use.CONCLUSION: Permethrin-treated clothing may be a promising intervention in reducing dengue transmission. However, our findings also suggest that clothing may provide only short-term protection due to the effect of washing and ironing, highlighting the need for improved fabric treatment techniques.
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17.
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18.
  • Dorlo, Thomas P C, et al. (author)
  • Dynamics of parasite clearance in cutaneous leishmaniasis patients treated with miltefosine.
  • 2011
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 5:12, s. e1436-
  • Journal article (peer-reviewed)abstract
    • Parasite loads were quantified in repeated skin biopsies from lesions of 2 patients with Old-World cutaneous leishmaniasis (CL) caused by Leishmania major and L. infantum during and after treatment with miltefosine. Miltefosine induced a rapid therapeutic effect on both infections with an initial decline of parasites of ∼1 log/week for the L. major infection. These observations illustrate the usability of quantifying parasite loads in skin lesions as a pharmacodynamic measure and quantitative descriptor of drug effect for CL supporting clinical assessment.
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19.
  • Dorlo, Thomas P C, et al. (author)
  • Pentamidine dosage : a base/salt confusion.
  • 2008
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 2:5, s. e225-
  • Journal article (peer-reviewed)abstract
    • Pentamidine has a long history in the treatment of human African trypanosomiasis (HAT) and leishmaniasis. Early guidelines on the dosage of pentamidine were based on the base-moiety of the two different formulations available. Confusion on the dosage of pentamidine arose from a different labelling of the two available products, either based on the salt or base moiety available in the preparation. We provide an overview of the various guidelines concerning HAT and leishmaniasis over the past decades and show the confusion in the calculation of the dosage of pentamidine in these guidelines and the subsequent published reports on clinical trials and reviews. At present, only pentamidine isethionate is available, but the advised dosage for HAT and leishmaniasis is (historically) based on the amount of pentamidine base. In the treatment of leishmaniasis this is probably resulting in a subtherapeutic treatment. There is thus a need for a new, more transparent and concise guideline concerning the dosage of pentamidine, at least in the treatment of HAT and leishmaniasis.
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20.
  • Duong, Veasna, et al. (author)
  • Clinical and virological factors influencing the performance of a NS1 antigen-capture assay and potential use as a marker of dengue disease severity
  • 2011
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science. - 1935-2727 .- 1935-2735. ; 5:7
  • Journal article (peer-reviewed)abstract
    • Background: Detection of dengue NS1 antigen in acute infection has been proposed for early diagnosis of dengue disease. The aim of this study was to evaluate the clinical and virological factors influencing the performance of the Platelia NS1 Ag kit (BioRad) and to assess the potential use of NS1 antigen and dengue viral loads as markers of dengue disease severity.Methodology/Principal Findings: Blood specimens were collected from patients hospitalized at the Kampong Cham hospital during the 2006 and 2007 dengue epidemics in Cambodia. Dengue infection was confirmed in 243/339 symptomatic patients and in 17 asymptomatic individuals out of 214 household members tested. Overall sensitivity and specificity of Platelia NS1 Ag kit were 57.5% and 100% respectively. NS1 Ag assay combined with IgM antibody capture ELISA significantly increased the sensitivity for dengue diagnosis. NS1 Ag positivity rate was found significantly higher in DF than in DHF/DSS, in primary than in secondary infections, in patients with a high viremia (>5 log/mL) and in patients infected with DENV-1. In asymptomatic individuals, the NS1 Ag capture sensitivity tends to be lower than that in symptomatic patients. Milder disease severity was observed independently in patients with RNA copy number >5 log10 cDNA equivalents/mL or in high level of NS1 antigen ratio or in DENV-1 infection.Conclusions: Overall sensitivity of NS1 Ag detection kit varied widely across the various forms of dengue infection or disease. Sensitivity was highest in patients sampled during the first 3 days after onset of fever, in patients with primary infection, DENV-1 infection, with high level of viremia and in DF rather than DHF/DSS. In asymptomatic patients, RT-PCR assay has proved to be more sensitive than NS1 antigen detection. The NS1 antigen level correlated significantly with viremia and a low NS1 antigen ratio was associated with more severe disease.Author Summary: Dengue is the most prevalent arthropod-borne disease in tropical regions. The clinical manifestation may vary from asymptomatic to potentially fatal dengue shock syndrome. Early laboratory confirmation of dengue diagnosis is essential since many symptoms are not specific. Dengue non-structural protein 1 (NS1) may be used in simple antigen-capture ELISA for early detection of dengue virus infection. Our result demonstrated that the Platelia NS1 antigen detection kit had a quite low overall sensitivity. However, sensitivity rises significantly when used in combination with MAC-ELISA. When taking into account the various forms of dengue infection, the NS1 antigen detection was found relatively high in patients sampled during the first 3 days of fever onset, in patients with primary infection, DENV-1 infection, with high level of viremia and in mild form of dengue fever. In asymptomatically infected individuals, RT-PCR assay has proved to be more sensitive than NS1 antigen detection. Moreover, the NS1 antigen level correlated significantly with high viremia and low level of NS1 antigen was associated with more severe disease.
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21.
  • Durrant, Jacob D., et al. (author)
  • Computational Identification of Uncharacterized Cruzain Binding Sites
  • 2010
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 4:5, s. e676-
  • Journal article (peer-reviewed)abstract
    • Chagas disease, caused by the unicellular parasite Trypanosoma cruzi, claims 50,000 lives annually and is the leading cause of infectious myocarditis in the world. As current antichagastic therapies like nifurtimox and benznidazole are highly toxic, ineffective at parasite eradication, and subject to increasing resistance, novel therapeutics are urgently needed. Cruzain, the major cysteine protease of Trypanosoma cruzi, is one attractive drug target. In the current work, molecular dynamics simulations and a sequence alignment of a non-redundant, unbiased set of peptidase C1 family members are used to identify uncharacterized cruzain binding sites. The two sites identified may serve as targets for future pharmacological intervention.
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22.
  • Eid Rodríguez, Daniel, et al. (author)
  • "Cheaper and better" : Societal cost savings and budget impact of changing from systemic to intralesional pentavalent antimonials as the first-line treatment for cutaneous leishmaniasis in Bolivia
  • 2019
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 13:11
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: Cutaneous leishmaniasis (CL), endemic in Bolivia, mostly affects poor people in rainforest areas. The current first-line treatment consists of systemic pentavalent antimonials (SPA) for 20 days and is paid for by the Ministry of Health (MoH). Long periods of drug shortages and a lack of safe conditions to deliver treatment are challenges to implementation. Intralesional pentavalent antimonials (ILPA) are an alternative to SPA. This study aims to compare the cost of ILPA and SPA, and to estimate the health and economic impacts of changing the first-line treatment for CL in a Bolivian endemic area.METHODS: The cost-per-patient treated was estimated for SPA and ILPA from the perspectives of the MoH and society. The quantity and unit costs of medications, staff time, transportation and loss of production were obtained through a health facility survey (N = 12), official documents and key informants. A one-way sensitivity analysis was conducted on key parameters to evaluate the robustness of the results. The annual number of patients treated and the budget impact of switching to ILPA as the first-line treatment were estimated under different scenarios of increasing treatment utilization. Costs were reported in 2017 international dollars (1 INT$ = 3.10 BOB).RESULTS: Treating CL using ILPA was associated with a cost-saving of $248 per-patient-treated from the MoH perspective, and $688 per-patient-treated from the societal perspective. Switching first-line treatment to ILPA while maintaining the current budget would allow two-and-a-half times the current number of patients to be treated. ILPA remained cost-saving compared to SPA in the sensitivity analysis.CONCLUSIONS: The results of this study support a shift to ILPA as the first-line treatment for CL in Bolivia and possibly in other South American countries.
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23.
  • Einarsson, Elin, et al. (author)
  • Coordinated Changes in Gene Expression Throughout Encystation of Giardia intestinalis
  • 2016
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 11:3
  • Journal article (peer-reviewed)abstract
    • Differentiation into infectious cysts through the process of encystation is crucial for transmission and survival of the intestinal protozoan parasite Giardia intestinalis. Hitherto the majority of studies have focused on the early events, leaving late encystation poorly defined. In order to further study encystation, focusing on the later events, we developed a new encystation protocol that generates a higher yield of mature cysts compared to standard methods. Transcriptome changes during the entire differentiation from trophozoites to cysts were thereafter studied using RNA sequencing (RNA-seq). A high level of periodicity was observed for up-and down-regulated genes, both at the level of the entire transcriptome and putative regulators. This suggests the trajectory of differentiation to be coordinated through developmentally linked gene regulatory activities. Our study identifies a core of 13 genes that are consistently up-regulated during initial encystation. Of these, two constitute previously uncharacterized proteins that we were able to localize to a new type of encystation-specific vesicles. Interestingly, the largest transcriptional changes were seen in the late phase of encystation with the majority of the highly up-regulated genes encoding hypothetical proteins. Several of these were epitope-tagged and localized to further characterize these previously unknown genetic components of encystation and possibly excystation. Finally, we also detected a switch of variant specific surface proteins (VSPs) in the late phase of encystation. This occurred at the same time as nuclear division and DNA replication, suggesting a potential link between the processes.
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24.
  • Franzen, Oscar, et al. (author)
  • The Short Non-Coding Transcriptome of the Protozoan Parasite Trypanosoma cruzi
  • 2011
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 5:8, s. e1283-
  • Journal article (peer-reviewed)abstract
    • The pathway for RNA interference is widespread in metazoans and participates in numerous cellular tasks, from gene silencing to chromatin remodeling and protection against retrotransposition. The unicellular eukaryote Trypanosoma cruzi is missing the canonical RNAi pathway and is unable to induce RNAi-related processes. To further understand alternative RNA pathways operating in this organism, we have performed deep sequencing and genome-wide analyses of a size-fractioned cDNA library (16-61 nt) from the epimastigote life stage. Deep sequencing generated 582,243 short sequences of which 91% could be aligned with the genome sequence. About 95-98% of the aligned data (depending on the haplotype) corresponded to small RNAs derived from tRNAs, rRNAs, snRNAs and snoRNAs. The largest class consisted of tRNA-derived small RNAs which primarily originated from the 3' end of tRNAs, followed by small RNAs derived from rRNA. The remaining sequences revealed the presence of 92 novel transcribed loci, of which 79 did not show homology to known RNA classes.
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25.
  • Guery, Romain, et al. (author)
  • Clinical diversity and treatment results in tegumentary leishmaniasis : A European clinical report in 459 patients
  • 2021
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 15:10
  • Journal article (peer-reviewed)abstract
    • Background Cutaneous leishmaniasis (CL) is frequent in travellers and can involve oro-nasal mucosae. Clinical presentation impacts therapeutic management. Methodology Demographic and clinical data from 459 travellers infected in 47 different countries were collected by members of the European LeishMan consortium. The infecting Leishmania species was identified in 198 patients. Principal findings Compared to Old World CL, New World CL was more frequently ulcerative (75% vs 47%), larger (3 vs 2cm), less frequently facial (17% vs 38%) and less frequently associated with mucosal involvement (2.7% vs 5.3%). Patients with mucosal lesions were older (58 vs 30 years) and more frequently immunocompromised (37% vs 3.5%) compared to patients with only skin lesions. Young adults infected in Latin America with L. braziliensis or L. guyanensis complex typically had an ulcer of the lower limbs with mucosal involvement in 5.8% of cases. Typically, infections with L. major and L. tropica acquired in Africa or the Middle East were not associated with mucosal lesions, while infections with L. infantum, acquired in Southern Europe resulted in slowly evolving facial lesions with mucosal involvement in 22% of cases. Local or systemic treatments were used in patients with different clinical presentations but resulted in similarly high cure rates (89% vs 86%). Conclusion/Significance CL acquired in L. infantum-endemic European and Mediterranean areas displays unexpected high rates of mucosal involvement comparable to those of CL acquired in Latin America, especially in immunocompromised patients. When used as per recommendations, local therapy is associated with high cure rates.
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26.
  • Ha, Tuyen V., et al. (author)
  • Spatial distribution of Culex mosquito abundance and associated risk factors in Hanoi, Vietnam
  • 2021
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 15:6
  • Journal article (peer-reviewed)abstract
    • Japanese encephalitis (JE) is the major cause of viral encephalitis (VE) in most AsianPacific countries. In Vietnam, there is no nationwide surveillance system for JE due to lack of medical facilities and diagnoses. Culex tritaeniorhynchus, Culex vishnui, and Culex quin-quefasciatus have been identified as the major JE vectors in Vietnam. The main objective of this study was to forecast a risk map of Culex mosquitoes in Hanoi, which is one of the most densely populated cities in Vietnam. A total of 10,775 female adult Culex mosquitoes were collected from 513 trapping locations. We collected temperature and precipitation information during the study period and its preceding month. In addition, the other predictor variables (e.g., normalized difference vegetation index [NDVI], land use/land cover and human population density), were collected for our analysis. The final model selected for estimating the Culex mosquito abundance included centered rainfall, quadratic term rainfall, rice cover ratio, forest cover ratio, and human population density variables. The estimated spatial distribution of Culex mosquito abundance ranged from 0 to more than 200 mosquitoes per 900m2. Our model estimated that 87% of the Hanoi area had an abundance of mosquitoes from 0 to 50, whereas approximately 1.2% of the area showed more than 150 mosquitoes, which was mostly in the rural/peri-urban districts. Our findings provide better insight into understanding the spatial distribution of Culex mosquitoes and its associated environmental risk factors. Such information can assist local clinicians and public health policymakers to identify potential areas of risk for JE virus. Risk maps can be an efficient way of raising public awareness about the virus and further preventive measures need to be considered in order to prevent outbreaks and onwards transmission of JE virus.
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27.
  • Hassan, Osama Ahmed, et al. (author)
  • The 2007 rift valley Fever outbreak in Sudan
  • 2011
  • In: PLoS Neglected Tropical Diseases. - San Francisco, CA : Public Library of Science. - 1935-2727 .- 1935-2735. ; 5:9
  • Research review (peer-reviewed)abstract
    • Rift Valley fever (RVF) is a neglected, emerging, mosquito-borne disease with severe negative impact on human and animal health and economy. RVF is caused by RVF virus (RVFV) affecting humans and a wide range of animals. The virus is transmitted through bites from mosquitoes and exposure to viremic blood, body fluids, or tissues of infected animals. During 2007 a large RVF outbreak occurred in Sudan with a total of 747 confirmed human cases including 230 deaths (case fatality 30.8%); although it has been estimated 75,000 were infected. It was most severe in White Nile, El Gezira, and Sennar states near to the White Nile and the Blue Nile Rivers. Notably, RVF was not demonstrated in livestock until after the human cases appeared and unfortunately, there are no records or reports of the number of affected animals or deaths. Ideally, animals should serve as sentinels to prevent loss of human life, but the situation here was reversed. Animal contact seemed to be the most dominant risk factor followed by animal products and mosquito bites. The Sudan outbreak followed an unusually heavy rainfall in the country with severe flooding and previous studies on RVF in Sudan suggest that RVFV is endemic in parts of Sudan. An RVF outbreak results in human disease, but also large economic loss with an impact beyond the immediate influence on the directly affected agricultural producers. The outbreak emphasizes the need for collaboration between veterinary and health authorities, entomologists, environmental specialists, and biologists, as the best strategy towards the prevention and control of RVF.
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28.
  • Hassan, Osama Ahmed, 1972-, et al. (author)
  • The One Health approach to identify knowledge, attitudes and practices that affect community involvement in the control of Rift Valley fever outbreaks
  • 2017
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 11:2
  • Journal article (peer-reviewed)abstract
    • Rift Valley fever (RVF) is a viral mosquito-borne disease with the potential for global expansion, causes hemorrhagic fever, and has a high case fatality rate in young animals and in humans. Using a cross-sectional community-based study design, we investigated the knowledge, attitudes and practices of people living in small village in Sudan with respect to RVF outbreaks. A special One Health questionnaire was developed to compile data from 235 heads of household concerning their knowledge, attitudes, and practices with regard to controlling RVF. Although the 2007 RVF outbreak in Sudan had negatively affected the participants' food availability and livestock income, the participants did not fully understand how to identify RVF symptoms and risk factors for both humans and livestock. For example, the participants mistakenly believed that avoiding livestock that had suffered spontaneous abortions was the least important risk factor for RVF. Although the majority noticed an increase in mosquito population during the 2007 RVF outbreak, few used impregnated bed nets as preventive measures. The community was reluctant to notify the authorities about RVF suspicion in livestock, a sentinel for human RVF infection. Almost all the respondents stressed that they would not receive any compensation for their dead livestock if they notified the authorities. In addition, the participants believed that controlling RVF outbreaks was mainly the responsibility of human health authorities rather than veterinary authorities. The majority of the participants were aware that RVF could spread from one region to another within the country. Participants received most their information about RVF from social networks and the mass media, rather than the health system or veterinarians. Because the perceived role of the community in controlling RVF was fragmented, the probability of RVF spread increased.
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29.
  • Hii, Yien Ling, et al. (author)
  • Forecast of dengue incidence using temperature and rainfall
  • 2012
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 6:11, s. e1908-
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: An accurate early warning system to predict impending epidemics enhances the effectiveness of preventive measures against dengue fever. The aim of this study was to develop and validate a forecasting model that could predict dengue cases and provide timely early warning in Singapore.METHODOLOGY AND PRINCIPAL FINDINGS: We developed a time series Poisson multivariate regression model using weekly mean temperature and cumulative rainfall over the period 2000-2010. Weather data were modeled using piecewise linear spline functions. We analyzed various lag times between dengue and weather variables to identify the optimal dengue forecasting period. Autoregression, seasonality and trend were considered in the model. We validated the model by forecasting dengue cases for week 1 of 2011 up to week 16 of 2012 using weather data alone. Model selection and validation were based on Akaike's Information Criterion, standardized Root Mean Square Error, and residuals diagnoses. A Receiver Operating Characteristics curve was used to analyze the sensitivity of the forecast of epidemics. The optimal period for dengue forecast was 16 weeks. Our model forecasted correctly with errors of 0.3 and 0.32 of the standard deviation of reported cases during the model training and validation periods, respectively. It was sensitive enough to distinguish between outbreak and non-outbreak to a 96% (CI = 93-98%) in 2004-2010 and 98% (CI = 95%-100%) in 2011. The model predicted the outbreak in 2011 accurately with less than 3% possibility of false alarm.SIGNIFICANCE: We have developed a weather-based dengue forecasting model that allows warning 16 weeks in advance of dengue epidemics with high sensitivity and specificity. We demonstrate that models using temperature and rainfall could be simple, precise, and low cost tools for dengue forecasting which could be used to enhance decision making on the timing, scale of vector control operations, and utilization of limited resources.
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30.
  • Hii, Yien Ling, et al. (author)
  • Optimal lead time for dengue forecast
  • 2012
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 6:10, s. e1848-
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: A dengue early warning system aims to prevent a dengue outbreak by providing an accurate prediction of a rise in dengue cases and sufficient time to allow timely decisions and preventive measures to be taken by local authorities. This study seeks to identify the optimal lead time for warning of dengue cases in Singapore given the duration required by a local authority to curb an outbreak.METHODOLOGY AND FINDINGS: We developed a Poisson regression model to analyze relative risks of dengue cases as functions of weekly mean temperature and cumulative rainfall with lag times of 1-5 months using spline functions. We examined the duration of vector control and cluster management in dengue clusters > = 10 cases from 2000 to 2010 and used the information as an indicative window of the time required to mitigate an outbreak. Finally, we assessed the gap between forecast and successful control to determine the optimal timing for issuing an early warning in the study area. Our findings show that increasing weekly mean temperature and cumulative rainfall precede risks of increasing dengue cases by 4-20 and 8-20 weeks, respectively. These lag times provided a forecast window of 1-5 months based on the observed weather data. Based on previous vector control operations, the time needed to curb dengue outbreaks ranged from 1-3 months with a median duration of 2 months. Thus, a dengue early warning forecast given 3 months ahead of the onset of a probable epidemic would give local authorities sufficient time to mitigate an outbreak.CONCLUSIONS: Optimal timing of a dengue forecast increases the functional value of an early warning system and enhances cost-effectiveness of vector control operations in response to forecasted risks. We emphasize the importance of considering the forecast-mitigation gaps in respective study areas when developing a dengue forecasting model.
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31.
  • Horstick, Olaf, et al. (author)
  • Reviewing dengue : still a neglected tropical disease?
  • 2015
  • In: PLoS Neglected Tropical Diseases. - : Public library science. - 1935-2727 .- 1935-2735. ; 9:4
  • Research review (peer-reviewed)abstract
    • Dengue is currently listed as a "neglected tropical disease" (NTD). But is dengue still an NTD or not? Classifying dengue as an NTD may carry advantages, but is it justified? This review considers the criteria for the definition of an NTD, the current diverse lists of NTDs by different stakeholders, and the commonalities and differences of dengue with other NTDs. We also review the current research gaps and research activities and the adequacy of funding for dengue research and development (R&D) (2003-2013). NTD definitions have been developed to a higher precision since the early 2000s, with the following main features: NTDs are characterised as a) poverty related, b) endemic to the tropics and subtropics, c) lacking public health attention, d) having poor research funding and shortcomings in R&D, e) usually associated with high morbidity but low mortality, and f) often having no specific treatment available. Dengue meets most of these criteria, but not all. Although dengue predominantly affects resource-limited countries, it does not necessarily only target the poor and marginalised in those countries. Dengue increasingly attracts public health attention, and in some affected countries it is now a high profile disease. Research funding for dengue has increased exponentially in the past two decades, in particular in the area of dengue vaccine development. However, despite advances in dengue research, dengue epidemics are increasing in frequency and magnitude, and dengue is expanding to new areas. Specific treatment and a highly effective vaccine remain elusive. Major research gaps exist in the area of integrated surveillance and vector control. Hence, although dengue differs from many of the NTDs, it still meets important criteria commonly used for NTDs. The current need for increased R& D spending, shared by dengue and other NTDs, is perhaps the key reason why dengue should continue to be considered an NTD.
  •  
32.
  • Höög, Johanna L, 1979, et al. (author)
  • 3D Architecture of the Trypanosoma brucei Flagella Connector, a Mobile Transmembrane Junction : Electron Tomography of the Flagella Connector
  • 2016
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 10:1
  • Journal article (peer-reviewed)abstract
    • Background Cellular junctions are crucial for the formation of multicellular organisms, where they anchor cells to each other and/or supportive tissue and enable cell-to-cell communication. Some unicellular organisms, such as the parasitic protist Trypanosoma brucei, also have complex cellular junctions. The flagella connector (FC) is a three-layered transmembrane junction that moves with the growing tip of a new flagellum and attaches it to the side of the old flagellum. The FC moves via an unknown molecular mechanism, independent of new flagellum growth. Here we describe the detailed 3D architecture of the FC suggesting explanations for how it functions and its mechanism of motility. Methodology/Principal Findings We have used a combination of electron tomography and cryo-electron tomography to reveal the 3D architecture of the FC. Cryo-electron tomography revealed layers of repetitive filamentous electron densities between the two flagella in the interstitial zone. Though the FC does not change in length and width during the growth of the new flagellum, the interstitial zone thickness decreases as the FC matures. This investigation also shows interactions between the FC layers and the axonemes of the new and old flagellum, sufficiently strong to displace the axoneme in the old flagellum. We describe a novel filament, the flagella connector fibre, found between the FC and the axoneme in the old flagellum. Conclusions/Significance The FC is similar to other cellular junctions in that filamentous proteins bridge the extracellular space and are anchored to underlying cytoskeletal structures; however, it is built between different portions of the same cell and is unique because of its intrinsic motility. The detailed description of its structure will be an important tool to use in attributing structure / function relationships as its molecular components are discovered in the future. The FC is involved in the inheritance of cell shape, which is important for the life cycle of this human parasite.
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33.
  •  
34.
  • Jakobsen, Frida, et al. (author)
  • Urban livestock-keeping and dengue in urban and peri-urban Hanoi, Vietnam.
  • 2019
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 13:11
  • Journal article (peer-reviewed)abstract
    • Urban livestock provides an important source of food and income, but it may increase the risks for disease transmission. Vectors, such as mosquitoes, might increase and thereby cause an enhanced transmission of infectious diseases, such as dengue fever; considered the most important mosquito-borne viral disease globally. This cross-sectional study evaluated the awareness of dengue fever and investigated how the presence of dengue vectors is affected by the keeping of livestock in urban households in the city of Hanoi, Vietnam. From February to March 2018, during the season of lowest occurrence of dengue in Hanoi, 140 households were interviewed, of which 69 kept livestock. A general trend was observed; respondents living in the Dan Phuong district, a peri-urban district, had better knowledge and practice regarding dengue as compared to the urban Ha Dong district. In total, 3899 mosquitoes were collected and identified, of which 52 (1.33%) were Aedes species. A significant difference between the two districts was observed, with more households in Ha Dong having Aedes spp. mosquitoes (p = 0.02) and a higher incidence of dengue fever (p = 0.001). There was no significant association between livestock-rearing and the presence of Aedes spp. mosquitoes (p = 0.955), or between livestock-rearing and the incidence of dengue fever (p = 0.08). In conclusion, this study could not find any indication that households keeping livestock were at higher risk of dengue virus infections in Hanoi during the season of lowest occurrence of dengue, but clearly indicated the need of more information provided to urban inhabitants, particularly on personal protection.
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35.
  • Jidling, Carl, et al. (author)
  • Screening for Chagas disease from the electrocardiogram using a deep neural network
  • 2023
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 17:7
  • Journal article (peer-reviewed)abstract
    • Chagas disease (ChD) is a neglected tropical disease, and the diagnosis relies on blood testing of patients from endemic areas. However, there is no clear recommendation on how to select patients for testing in endemic regions. Since most cases of Chronic ChD are asymptomatic, the diagnostic rates are low, preventing patients from receiving adequate treatment.The Electrocardiogram (ECG) is a widely available, low-cost exam, often available in primary care settings. We present an Artificial intelligence (AI) model for automatically detecting ChD from the ECG. AI algorithms have allowed the detection of hidden conditions on the ECG and, to the best of our knowledge, this is the first study that does it for ChD. We utilize large cohorts of patients from the relevant population of all-comers in affected regions in Brazil to develop a model for ChD detection that is then validated on datasets with ground truth labels obtained directly from the patients’ serological status.Our findings demonstrate a promising AI-ECG-based model for discriminating patients with chronic Chagas cardiomyopathy (CCC). The capacity of detecting ChD patients without CCC is still limited. But we believe this can be improved with the addition of epidemiological questions, and that such models can become useful tools for pre-selecting patients for further testing.
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36.
  • Jin, Jing, et al. (author)
  • An attenuated replication-competent chikungunya virus with a fluorescently tagged envelope
  • 2018
  • In: PLoS Neglected Tropical Diseases. - : PUBLIC LIBRARY SCIENCE. - 1935-2727 .- 1935-2735. ; 12:7
  • Journal article (peer-reviewed)abstract
    • Background: Chikungunya virus (CHIKV) is the most common alphavirus infecting humans worldwide, causing acute and chronically debilitating arthralgia at a great economic expense.Methodology/Principal findings: To facilitate our study of CHIKV, we generated a mCherry tagged replication-competent chimeric virus, CHIKV 37997-mCherry. Single particle cryoEM demonstrated icosahedral organization of the chimeric virus and the display of mCherry proteins on virus surface. CHIKV 37997-mCherry is attenuated in both IFN alpha R knockout and wild-type mice. Strong antiCHIKV and anti-mCherry antibody responses were induced in CHIKV 37997-mCherry infected mice.Conclusions/Significance: Our work suggests that chimeric alphaviruses displaying foreign antigen can serve as vaccines against both aphaviruses and other pathogens and diseases.
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37.
  • Kairu-Wanyoike, Salome, et al. (author)
  • Positive association between Brucella spp. seroprevalences in livestock and humans from a cross-sectional study in Garissa and Tana River Counties, Kenya.
  • 2019
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 13:10
  • Journal article (peer-reviewed)abstract
    • 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.
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38.
  • Kamuyu, Gathoni, et al. (author)
  • Exposure to Multiple Parasites Is Associated with the Prevalence of Active Convulsive Epilepsy in Sub-Saharan Africa
  • 2014
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 8:5
  • Journal article (peer-reviewed)abstract
    • Background: Epilepsy is common in developing countries, and it is often associated with parasitic infections. We investigated the relationship between exposure to parasitic infections, particularly multiple infections and active convulsive epilepsy (ACE), in five sites across sub-Saharan Africa. Methods and Findings: A case-control design that matched on age and location was used. Blood samples were collected from 986 prevalent cases and 1,313 age-matched community controls and tested for presence of antibodies to Onchocerca volvulus, Toxocara canis, Toxoplasma gondii, Plasmodium falciparum, Taenia solium and HIV. Exposure (seropositivity) to Onchocerca volvulus (OR = 1.98; 95% CI: 1.52-2.58, p<0.001), Toxocara canis (OR = 1.52; 95% CI: 1.23-1.87, p<0.001), Toxoplasma gondii (OR = 1.28; 95% CI: 1.04-1.56, p=0.018) and higher antibody levels (top tertile) to Toxocara canis (OR = 1.70; 95% CI: 1.30-2.24, p<0.001) were associated with an increased prevalence of ACE. Exposure to multiple infections was common (73.8% of cases and 65.5% of controls had been exposed to two or more infections), and for T. gondii and O. volvulus co-infection, their combined effect on the prevalence of ACE, as determined by the relative excess risk due to interaction (RERI), was more than additive (T. gondii and O. volvulus, RERI = 1.19). The prevalence of T. solium antibodies was low (2.8% of cases and 2.2% of controls) and was not associated with ACE in the study areas. Conclusion: This study investigates how the degree of exposure to parasites and multiple parasitic infections are associated with ACE and may explain conflicting results obtained when only seropositivity is considered. The findings from this study should be further validated.
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39.
  • Kesik-Brodacka, Malgorzata, et al. (author)
  • Immune response of rats vaccinated orally with various plant-expressed recombinant cysteine proteinase constructs when challenged with Fasciola hepatica metacercariae
  • 2017
  • In: PLoS Neglected Tropical Diseases. - : PUBLIC LIBRARY SCIENCE. - 1935-2727 .- 1935-2735. ; 11:3
  • Journal article (peer-reviewed)abstract
    • Background Cysteine proteinases of Fasciola hepatica are important candidates for vaccine antigens because of their role in fluke biology and host-parasite relationships. In our previous experiments, we found that a recombinant cysteine proteinase cloned from adult F. hepatica ( CPFhW) can protect rats against liver fluke infections when it is administered intramuscularly or intranasally in the form of cDNA. We also observed considerable protection upon challenge following mucosal vaccination with inclusion bodies containing recombinant CPFhW produced in Escherichia coli. In this study, we explore oral vaccination, which may be the desired method of delivery and is potentially capable of preventing infections at the site of helminth entry. To provide antigen encapsulation and to protect the vaccine antigen from degradation in the intestinal tract, transgenic plant-based systems are used. Methodology Conclusions We obtained substantial protection after oral administration of the plant-produced hybrids of CPFhW and HBcAg. The highest level of protection (65.4%)was observed in animals immunised with transgenic plants expressing the mature CPFhW enzyme flanked by Gly-rich linkers and inserted into c/e1 epitope of truncated HBcAg. The immunised rats showed clear IgG1 and IgM responsesIn the present study, we aimed to evaluate the protective ability of mucosal vaccinations of 12-week- old rats with CPFhW produced in a transgenic-plant-based system. To avoid inducing tolerance and to maximise the immune response induced by oral immunisation, we used the hepatitis B virus (HBV) core protein ( HBcAg) as a carrier. Animals were immunised with two doses of the antigen and challenged with 25 or 30 metacercariae of F. hepatica. Conclusions We obtained substantial protection after oral administration of the plant-produced hybrids of CPFhW and HBcAg. The highest level of protection (65.4%) was observed in animals immunised with transgenic plants expressing the mature CPFhW enzyme flanked by Gly- rich linkers and inserted into c/e1 epitope of truncated HBcAg. The immunised rats showed clear IgG1 and IgM responses to CPFhW for 4 consecutive weeks after the challenge.
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40.
  • Khalil, Eltahir A G, et al. (author)
  • Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa : a randomised trial.
  • 2014
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 8:1, s. e2613-
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Anti-leishmanial drug regimens that include a single dose AmBisome could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown.METHODOLOGY: A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and multiple doses of AmBisome for the treatment of VL in eastern Africa. The primary efficacy endpoint was definitive cure (DC) at 6 months. Symptomatic patients with parasitologically-confirmed, non-severe VL, received a single dose of AmBisome 7.5 mg/kg body weight or multiple doses, 7 times 3 mg/kg on days 1-5, 14, and 21. If interim analyses, evaluated 30 days after the start of treatment following 40 or 80 patients, showed the single dose gave significantly poorer parasite clearance than multiple doses at the 5% significance level, the single dose was increased by 2·5 mg/kg. In a sub-set of patients, parasite clearance was measured by quantitative reverse transcriptase (qRT) PCR.PRINCIPAL FINDINGS: The trial was terminated after the third interim analysis because of low efficacy of both regimens. Based on the intention-to-treat population, DC was 85% (95%CI 73-93%), 40% (95%CI 19-64%), and 58% (95%CI 41-73%) in patients treated with multiple doses (n = 63), and single doses of 7·5 (n = 21) or 10 mg/kg (n = 40), respectively. qRT-PCR suggested superior parasite clearance with multiple doses as early as day 3. Safety data accorded with the drug label.CONCLUSIONS: The tested AmBisome regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified.TRIALS REGISTRATION: www.clinicaltrials.govNCT00832208.
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41.
  • Khalil, Hussein (author)
  • Poverty, sanitation, and Leptospira transmission pathways in residents from four Brazilian slums
  • 2021
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 15
  • Journal article (peer-reviewed)abstract
    • Author summaryGlobally, more than 1 billion residents live in urban slums, where inadequate sanitation increases the spread of pathogens and their animal hosts. Leptospirosis is a globally distributed bacterial disease, and in urban areas the bacteria is spread by brown rats. Humans become infected upon exposure to water or soil/mud that was contaminated with the urine of infected rats. In four urban slums in the city of Salvador, Brazil, we used a range of individual, socioeconomic, and environmental variables to understand how they influence to one another and define o leptospirosis exposure in residents. Poverty and sanitation influenced the degree to which residents were exposed to sewer water and mud. Further, we found that while residents tried to improve the physical environment near their household, living in an area with poor sanitation mean that their infection risk remained high. This work highlight the importance of socioeconomic and environmental factors in determining disease risk, and suggests that governmental interventions should focus on improving sanitation changes in the poorest parts of the community.Residents of urban slums suffer from a high burden of zoonotic diseases due to individual, socioeconomic, and environmental factors. We conducted a cross-sectional sero-survey in four urban slums in Salvador, Brazil, to characterize how poverty and sanitation contribute to the transmission of rat-borne leptospirosis. Sero-prevalence in the 1,318 participants ranged between 10.0 and 13.3%. We found that contact with environmental sources of contamination, rather than presence of rat reservoirs, is what leads to higher risk for residents living in areas with inadequate sanitation. Further, poorer residents may be exposed away from the household, and ongoing governmental interventions were not associated with lower transmission risk. Residents at higher risk were aware of their vulnerability, and their efforts improved the physical environment near their household, but did not reduce their infection chances. This study highlights the importance of understanding the socioeconomic and environmental determinants of risk, which ought to guide intervention efforts.
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42.
  • Kiflie, Amare, et al. (author)
  • Helminth species-specific effects on IFN-gamma producing T cells during active and latent tuberculosis
  • 2023
  • In: PLoS Neglected Tropical Diseases. - : PUBLIC LIBRARY SCIENCE. - 1935-2727 .- 1935-2735. ; 17:1
  • Journal article (peer-reviewed)abstract
    • BackgroundInterferon-gamma (IFN-gamma) is a key cytokine inducing protective immune responses during tuberculosis (TB) infection. Helminth-induced immune responses may affect IFN-gamma production by T cells, although its connection with disease severity and immune recovery during treatment is unexplored. We investigated the species-specific effect of helminths on the IFN-gamma production by T cells in relation to disease severity during active and latent TB infection (LTBI). MethodsIn this study, 69 active pulmonary TB patients (PTB), 28 with LTBI and 66 healthy controls were included. Active TB was diagnosed using GenXpert MTB/RIF while QuantiFERON test (QFT) was used for the screening of healthy community controls (CCs) and for the diagnosis of LTBI. Helminth infection was identified by routine diagnosis whereas clinical disease severity was evaluated by the TB score. Intracellular IFN-gamma production of T cells in stimulated peripheral blood mononuclear cells (PBMCs) was analyzed by flow cytometry using TB antigens (PPD), the polyclonal T cell activator staphylococcal enterotoxin B (SEB), or medium as unstimulated control. ResultsHelminth infected CCs and LTBI subjects showed a significant reduction of IFN-gamma(+) CD4(+) T cells by PPD-stimulation compared to non-helminth infected control groups. The significant reduction in the frequency of IFN-gamma(+) T cells in both latent and active PTB patients following SEB stimulation was mostly attributed to Schistosoma mansoni infection, whereas Ascaris lumbricoides, Schistosoma mansoni, and hookworm infection contributed equally in CCs. Following anti-helminthic and anti-TB treatment for 2 months, the frequency of IFN-gamma(+) CD4 T cells in helminth coinfected PTB was restored to levels of helminth negative PTB before treatment. Helminth coinfected PTB patients with an intermediate and severe clinical course had reduced capacity for production of IFN-gamma(+) T cells compared to the corresponding non-helminth infected PTB. ConclusionWe found a reduction in IFN-gamma producing T cells by helminth coinfection which was restored following anti-helminthic treatment. This reduction was helminth species-dependent in an exploratory sub-analysis and correlated to increased disease severity. Author summaryProtective immunity against tuberculosis (TB) requires a Th-1 response with cytokines like TNF and IFN-gamma which plays a key role in the recruitment and activation of immune cells. Helminth infection, on the other hand, can lead to induction of regulatory T cells and a Th-2 skewed response decreasing IFN-gamma in T cells. Decreased Th-1 responses could favor reactivation of latent TB infection (LTBI), although the helminth species-specific effect on IFN-gamma(+)CD4(+) T cells and the link to TB disease severity in patients with active pulmonary TB (PTB) have not been fully investigated. Therefore, blood cells (PBMCs) from healthy controls, LTBI individuals, and PTB patients were used to evaluate the impact of different helminths on the frequency of IFN-gamma(+)CD4(+) T cells, in Gondar Ethiopia. Ascaris lumbricoides, Schistosoma mansoni, and hookworm infection in healthy controls contributed equally to decreasing the frequency of IFN-gamma(+)CD4(+) T cells, whereas in both LTBI and PTB patients S. mansoni coinfection had the greatest impact on reducing IFN-gamma producing capacity of T cells. Decreased IFN-gamma producing capacity of T cells was correlated with increased TB disease severity, only in helminth coinfected PTB patients, and anti-helminthic therapy restored the IFN-gamma producing capacity of T cells at the 2 months follow-up.
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43.
  • Kinsman, John, et al. (author)
  • Development of a set of community-informed Ebola messages for Sierra Leone
  • 2017
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 11:8
  • Journal article (peer-reviewed)abstract
    • The West African Ebola epidemic of 2013-2016 was by far the largest outbreak of the disease on record. Sierra Leone suffered nearly half of the 28,646 reported cases. This paper presents a set of culturally contextualized Ebola messages that are based on the findings of qualitative interviews and focus group discussions conducted in 'hotspot' areas of rural Bombali District and urban Freetown in Sierra Leone, between January and March 2015. An iterative approach was taken in the message development process, whereby (i) data from formative research was subjected to thematic analysis to identify areas of community concern about Ebola and the national response; (ii) draft messages to address these concerns were produced; (iii) the messages were field tested; (iv) the messages were refined; and (v) a final set of messages on 14 topics was disseminated to relevant national and international stakeholders. Each message included details of its rationale, audience, dissemination channels, messengers, and associated operational issues that need to be taken into account. While developing the 14 messages, a set of recommendations emerged that could be adopted in future public health emergencies. These included the importance of embedding systematic, iterative qualitative research fully into the message development process; communication of the subsequent messages through a two-way dialogue with communities, using trusted messengers, and not only through a one-way, top-down communication process; provision of good, parallel operational services; and engagement with senior policy makers and managers as well as people in key operational positions to ensure national ownership of the messages, and to maximize the chance of their being utilised. The methodological approach that we used to develop our messages along with our suggested recommendations constitute a set of tools that could be incorporated into international and national public health emergency preparedness and response plans.
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44.
  • Kittayapong, Pattamaporn, et al. (author)
  • Mitigating Diseases Transmitted by Aedes Mosquitoes : A Cluster-Randomised Trial of Permethrin-Impregnated School Uniforms
  • 2017
  • In: PLoS Neglected Tropical Diseases. - : Public Library Service. - 1935-2727 .- 1935-2735. ; 11:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Viral diseases transmitted via Aedes mosquitoes are on the rise, such as Zika, dengue, and chikungunya. Novel tools to mitigate Aedes mosquitoes-transmitted diseases are urgently needed. We tested whether commercially insecticide-impregnated school uniforms can reduce dengue incidence in school children.METHODS: We designed a cluster-randomised controlled trial in Thailand. The primary endpoint was laboratory-confirmed dengue infections. Secondary endpoints were school absenteeism; and impregnated uniforms' 1-hour knock-down and 24 hour mosquito mortality as measured by standardised WHOPES bioassay cone tests at baseline and after repeated washing. Furthermore, entomological assessments inside classrooms and in outside areas of schools were conducted.RESULTS: We enrolled 1,811 pupils aged 6-17 from 5 intervention and 5 control schools. Paired serum samples were obtained from 1,655 pupils. In the control schools, 24/641 (3.7%) and in the intervention schools 33/1,014 (3.3%) students had evidence of new dengue infections during one school term (5 months). There was no significant difference in proportions of students having incident dengue infections between the intervention and control schools, with adjustment for clustering by school. WHOPES cone tests showed a 100% knock down and mortality of Aedes aegypti mosquitoes exposed to impregnated clothing at baseline and up to 4 washes, but this efficacy rapidly declined to below 20% after 20 washes, corresponding to a weekly reduction in knock-down and mosquito mortality by 4.7% and 4.4% respectively. Results of the entomological assessments showed that the mean number of Aedes aegypti mosquitoes caught inside the classrooms of the intervention schools was significantly reduced in the month following the introduction of the impregnated uniforms, compared to those collected in classrooms of the control schools (p = 0.04).CONCLUSIONS: Entomological assessments showed that the intervention had some impact on the number of Aedes mosquitoes inside treatment schools immediately after impregnation and before insecticidal activity declined. However, there was no serological evidence of protection against dengue infections over the five months school term, best explained by the rapid washing-out of permethrin after 4 washes. If rapid washing-out of permethrin could be overcome by novel technological approaches, insecticide-treated clothes might become a potentially cost-effective and scalable intervention to protect against diseases transmitted by Aedes mosquitoes such as dengue, Zika, and chikungunya.TRIAL REGISTRATION: ClinicalTrials.gov NCT01563640.
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45.
  • Larsson, Christer, 1975-, et al. (author)
  • A novel animal model of Borrelia recurrentis louse-borne relapsing fever borreliosis using immunodeficient mice
  • 2009
  • In: PLoS Neglected Tropical Diseases. - : PLoS, Public Library of Science. - 1935-2727 .- 1935-2735. ; 3:9, s. e522-
  • Journal article (peer-reviewed)abstract
    • Louse-borne relapsing fever (LBRF) borreliosis is caused by Borrelia recurrentis, and it is a deadly although treatable disease that is endemic in the Horn of Africa but has epidemic potential. Research on LBRF has been severely hampered because successful infection with B. recurrentis has been achieved only in primates (i.e., not in other laboratory or domestic animals). Here, we present the first non-primate animal model of LBRF, using SCID (-B, -T cells) and SCID BEIGE (-B, -T, -NK cells) immunocompromised mice. These animals were infected with B. recurrentis A11 or A17, or with B. duttonii 1120K3 as controls. B. recurrentis caused a relatively mild but persistent infection in SCID and SCID BEIGE mice, but did not proliferate in NUDE (-T) and BALB/c (wild-type) mice. B. duttonii was infectious but not lethal in all animals. These findings demonstrate that the immune response can limit relapsing fever even in the absence of humoral defense mechanisms. To study the significance of phagocytic cells in this context, we induced systemic depletion of such cells in the experimental mice by injecting them with clodronate liposomes, which resulted in uncontrolled B. duttonii growth and a one-hundred-fold increase in B. recurrentis titers in blood. This observation highlights the role of macrophages and other phagocytes in controlling relapsing fever infection. B. recurrentis evolved from B. duttonii to become a primate-specific pathogen that has lost the ability to infect immunocompetent rodents, probably through genetic degeneration. Here, we describe a novel animal model of B. recurrentis based on B- and T-cell-deficient mice, which we believe will be very valuable in future research on LBRF. Our study also reveals the importance of B-cells and phagocytes in controlling relapsing fever infection.
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46.
  • Laurent, Timothée, et al. (author)
  • The organization of double-stranded RNA in the chikungunya virus replication organelle
  • 2023
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 17:7
  • Journal article (peer-reviewed)abstract
    • Alphaviruses are mosquito-borne, positive-sense single-stranded RNA viruses. Amongst the alphaviruses, chikungunya virus is notable as a large source of human illness, especially in tropical and subtropical regions. When they invade a cell, alphaviruses generate dedicated organelles for viral genome replication, so-called spherules. Spherules form as outward-facing buds at the plasma membrane, and it has recently been shown that the thin membrane neck that connects this membrane bud with the cytoplasm is guarded by a two-megadalton protein complex that contains all the enzymatic functions necessary for RNA replication. The lumen of the spherules contains a single copy of the negative-strand template RNA, present in a duplex with newly synthesized positive-sense RNA. Less is known about the organization of this double-stranded RNA as compared to the protein components of the spherule. Here, we analyzed cryo-electron tomograms of chikungunya virus spherules in terms of the organization of the double-stranded RNA replication intermediate. We find that the double-stranded RNA has a shortened apparent persistence length as compared to unconstrained double-stranded RNA. Around half of the genome is present in either of five conformations identified by subtomogram classification, each representing a relatively straight segment of ~25–32 nm. Finally, the RNA occupies the spherule lumen at a homogeneous density, but has a preferred orientation to be perpendicular to a vector pointing from the membrane neck towards the spherule center. Taken together, this analysis lays another piece of the puzzle of the highly coordinated alphavirus genome replication.
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47.
  • Lebbad, Marianne, et al. (author)
  • Multilocus Genotyping of Human Giardia Isolates Suggests Limited Zoonotic Transmission and Association between Assemblage B and Flatulence in Children
  • 2011
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 5:8, s. e1262-
  • Journal article (peer-reviewed)abstract
    • Background: Giardia intestinalis is one of the most common diarrhea-related parasites in humans, where infection ranges from asymptomatic to acute or chronic disease. G. intestinalis consists of eight genetically distinct genotypes or assemblages, designated A-H, and assemblages A and B can infect humans. Giardiasis has been classified as a possible zoonotic disease but the role of animals in human disease transmission still needs to be proven. We tried to link different assemblages and sub-assemblages of G. intestinalis isolates from Swedish human patients to clinical symptoms and zoonotic transmission. Methodology/Principal Findings: Multilocus sequence-based genotyping of 207 human Giardia isolates using three gene loci: beta-giardin, glutamate dehydrogenase (gdh), and triose phosphate isomerase (tpi) was combined with assemblage-specific tpi PCRs. This analysis identified 73 patients infected with assemblage A, 128 with assemblage B, and six with mixed assemblages A+B. Multilocus genotypes (MLGs) were easily determined for the assemblage A isolates, and most patients with this genotype had apparently been infected through anthroponotic transmission. However, we also found evidence of limited zoonotic transmission of Giardia in Sweden, since a few domestic human infections involved the same assemblage A MLGs previously reported in Swedish cats and ruminants. Assemblage B was detected more frequently than assemblage A and it was also more common in patients with suspected treatment failure. However, a large genetic variability made determination of assemblage B MLGs problematic. Correlation between symptoms and assemblages was found only for flatulence, which was significantly more common in children less than six years of age infected with assemblage B. Conclusions/Significance: This study shows that certain assemblage A subtypes are potentially zoonotic and that flatulence is connected to assemblage B infections in young children. Determination of MLGs from assemblages A and B can be a valuable tool in outbreak situations and to help identify possible zoonotic transmission.
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48.
  • Lindahl, Johanna (author)
  • A systematic review and meta-analysis of the aetiological agents of non-malarial febrile illnesses in Africa
  • 2022
  • In: PLoS Neglected Tropical Diseases. - 1935-2727 .- 1935-2735. ; 16
  • Journal article (peer-reviewed)abstract
    • BackgroundThe awareness of non-malarial febrile illnesses (NMFIs) has been on the rise over the last decades. Therefore, we undertook a systematic literature review and meta-analysis of causative agents of non-malarial fevers on the African continent.MethodologyWe searched for literature in African Journals Online, EMBASE, PubMed, Scopus, and Web of Science databases to identify aetiologic agents that had been reported and to determine summary estimates of the proportional morbidity rates (PMr) associated with these pathogens among fever patients.FindingsA total of 133 studies comprising 391,835 patients from 25 of the 54 African countries were eligible. A wide array of aetiologic agents were described with considerable regional differences among the leading agents. Overall, bacterial pathogens tested from blood samples accounted for the largest proportion. The summary estimates from the meta-analysis were low for most of the agents. This may have resulted from a true low prevalence of the agents, the failure to test for many agents or the low sensitivity of the diagnostic methods applied. Our meta-regression analysis of study and population variables showed that diagnostic methods determined the PMr estimates of typhoidal Salmonella and Dengue virus. An increase in the PMr of Klebsiella spp. infections was observed over time. Furthermore, the status of patients as either inpatient or outpatient predicted the PMr of Haemophilus spp. infections.ConclusionThe small number of epidemiological studies and the variety of NMFI agents on the African continent emphasizes the need for harmonized studies with larger sample sizes. In particular, diagnostic procedures for NMFIs should be standardized to facilitate comparability of study results and to improve future meta-analyses. Reliable NMFI burden estimates will inform regional public health strategies.
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49.
  • Lindahl, Johanna, et al. (author)
  • Circulation of Japanese Encephalitis Virus in Pigs and Mosquito Vectors within Can Tho City, Vietnam
  • 2013
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 7
  • Journal article (peer-reviewed)abstract
    • Japanese encephalitis virus (JEV) is a mosquito-borne, zoonotic flavivirus causing encephalitis in humans and reproductive disorder in pigs. JEV is present in large parts of Asia, where urbanization is high. Households within and outside Can Tho city, South Vietnam, were selected to monitor circulation of JEV. A nested RT-PCR was established to detect the presence of JEV in mosquitoes whereas sera from pigs belonging to households within the province were analyzed for the presence of antibodies to JEV. A total of 7885 mosquitoes were collected and divided into 352 pools whereof seven were JEV-positive, six of which were collected within the city. Fragments from four pools clustered with JEV genotype III and three with genotype I. Of the 43 pigs sampled inside the city 100% had JEV antibodies. Our study demonstrates exposure to JEV in pigs, and co-circulation of JEV genotype I and III in mosquitoes within an urban environment in South Vietnam. Thus, although JEV has mainly been considered a rural disease, the potential for transmission in urban areas cannot be ignored.
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50.
  • Lindahl Rajala, Elisabeth, et al. (author)
  • Detection and characterization of Brucella spp. in bovine milk in small-scale urban and peri-urban farming in Tajikistan
  • 2017
  • In: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 11:3
  • Journal article (peer-reviewed)abstract
    • Brucellosis is one of the most common zoonoses globally, and Central Asia remains a Brucella hotspot. The World Health Organization classifies brucellosis as a neglected zoonotic disease that is rarely in the spotlight for research and mainly affects poor, marginalized people. Urban and peri-urban farming is a common practice in many low-income countries, and it increases the incomes of families that are often restrained by limited economic resources. However, there is a concern that the growing number of people and livestock living close together in these areas will increase the transmission of zoonotic pathogens such as Brucella. This study investigates the presence of Brucella DNA in bovine milk in the urban and peri-urban area of Dushanbe, Tajikistan. Brucella DNA was detected in 10.3% of 564 cow milk samples by IS711-based real-time PCR. This finding is concerning because consumption of unpasteurized dairy products is common in the region. Furthermore, Brucella DNA was detected in the milk of all seropositive cows, but 8.3% of the seronegative cows also showed the presence of Brucella DNA. In addition, sequence analysis of the rpoB gene suggests that one cow was infected with B. abortus and another cow was most likely infected with B. melitensis. The discrepancies between the serology and real-time PCR results highlight the need to further investigate whether there is a need for implementing complementary diagnostic strategies to detect false serological negative individuals in Brucella surveillance, control, and eradication programmes. Furthermore, vaccination of cattle with S19 in addition to vaccination of small ruminants with Rev 1 might be needed in order to control Brucella infections in the livestock population but further research focusing on the isolation of Brucella is required to obtain a comprehensive understanding of the Brucella spp. circulating among the livestock in this region.
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