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Gastrointestinal disseminated histoplasmosis in HIV-infected patients: A descriptive and comparative study

PLoS Neglected Tropical Diseases News - 22 January 2021 - 2:00pm

by Mathieu Nacher, Audrey Valdes, Antoine Adenis, Romain Blaizot, Philippe Abboud, Magalie Demar, Félix Djossou, Loïc Epelboin, Caroline Misslin, Balthazar Ntab, Dominique Louvel, Kinan Drak Alsibai, Pierre Couppié

Disseminated histoplasmosis is one the main AIDS-defining opportunistic infections in HIV-infected patients, notably in Latin America. The non-specific and proteiform clinical presentation leads to diagnostic delays that may lead to fatal outcomes. This retrospective multicentric study aimed to describe the frequency and manifestations of gastrointestinal histoplasmosis in French Guiana, and to compare patients with disseminated histoplasmosis with or without gastrointestinal involvement. Between January 1, 1981 and October 1, 2014 co-infections with HIV and histoplasmosis were enrolled. Inclusion criteria were: age >18 years, confirmed HIV infection; first proven episode of histoplasmosis. Among 349 cases of disseminated histoplasmosis, 245 (70%) had a gastrointestinal presentation. Half of patients with gastrointestinal signs had abdominal pain or diarrhea, mostly watery. Half of patients with abdominal pain had diarrhea (63/124) and half of those with diarrhea (63/123) had abdominal pain. A significant proportion of patients also had hepatomegaly and, to a lesser degree, splenomegaly. After adjusting for potential confounding, the presence of lymphadenopathies >2cm (AOR = 0.2, IC95 = 0.04–0.7, P = 0.01), Haitian origin (AOR = 0.04, IC95 = 0.004–0.4, P = 0.006) were associated with a lower prevalence of gastrointestinal signs and positive gastrointestinal presence of H. capsulatum. Persons with a gastrointestinal H. capsulatum were more likely to have a decreased prothrombin time, lower ferritin, lower liver enzymes, and lower concentrations of LDH than those without gastrointestinal signs and symptoms. They also had a shorter interval between symptoms onset and diagnosis. Patients with a positive gastrointestinal identification of H. capsulatum were less likely to die at 1 month than those without a gastrointestinal presentation (respectively, 4.6% vs 18.5%, P = 0.01). Subacute or chronic gastrointestinal presentations are very frequent during disseminated histoplasmosis, they seem less severe, and should lead to suspect the diagnosis in endemic areas. There were populational or geographic differences in the frequency of gastrointestinal manifestations that could not be explained.

Integrating human behavior and snake ecology with agent-based models to predict snakebite in high risk landscapes

PLoS Neglected Tropical Diseases News - 22 January 2021 - 2:00pm

by Eyal Goldstein, Joseph J. Erinjery, Gerardo Martin, Anuradhani Kasturiratne, Dileepa Senajith Ediriweera, Hithanadura Janaka de Silva, Peter Diggle, David Griffith Lalloo, Kris A. Murray, Takuya Iwamura

Snakebite causes more than 1.8 million envenoming cases annually and is a major cause of death in the tropics especially for poor farmers. While both social and ecological factors influence the chance encounter between snakes and people, the spatio-temporal processes underlying snakebites remain poorly explored. Previous research has heavily focused on statistical correlates between snakebites and ecological, sociological, or environmental factors, but the human and snake behavioral patterns that drive the spatio-temporal process have not yet been integrated into a single model. Here we use a bottom-up simulation approach using agent-based modelling (ABM) parameterized with datasets from Sri Lanka, a snakebite hotspot, to characterise the mechanisms of snakebite and identify risk factors. Spatio-temporal dynamics of snakebite risks are examined through the model incorporating six snake species and three farmer types (rice, tea, and rubber). We find that snakebites are mainly climatically driven, but the risks also depend on farmer types due to working schedules as well as species present in landscapes. Snake species are differentiated by both distribution and by habitat preference, and farmers are differentiated by working patterns that are climatically driven, and the combination of these factors leads to unique encounter rates for different landcover types as well as locations. Validation using epidemiological studies demonstrated that our model can explain observed patterns, including temporal patterns, and relative contribution of bites by each snake specie. Our predictions can be used to generate hypotheses and inform future studies and decision makers. Additionally, our model is transferable to other locations with high snakebite burden as well.

Diagnosis of soil-transmitted helminths using the Kato-Katz technique: What is the influence of stirring, storage time and storage temperature on stool sample egg counts?

PLoS Neglected Tropical Diseases News - 22 January 2021 - 2:00pm

by Felix Bosch, Marta S. Palmeirim, Said M. Ali, Shaali M. Ame, Jan Hattendorf, Jennifer Keiser

Background

Soil-transmitted helminths infect about one ninth of the world’s population and have a negative impact on health. The Kato-Katz technique is the recommended method to detect soil-transmitted helminth eggs in stool samples particularly in programmatic settings however, some questions in its procedure remain. Our study aimed to study the effect of storage time, storage temperature and stirring of stool samples on fecal egg counts (FECs).

Methodology/Principal findings

In the framework of a clinical trial on Pemba Island, United Republic of Tanzania, 488 stool samples were collected from schoolchildren, which were evaluated in three experiments. In the first experiment (n = 92), two Kato-Katz slides were prepared from the same stool sample, one was stored at room temperature and the other in a refrigerator for up to 50 hours, and each slide was analyzed at nine time points (20, 50, 80, 110, 140 minutes, 18, 26, 42 and 50 hours). In the second experiment (n = 340), whole stool samples were split into two, one part was stored at room temperature and the other in a refrigerator for up to 48 hours. From each part one Kato-Katz slide was prepared and analyzed at three time points over two days (0, 24 and 48 hours). In the third experiment (n = 56), whole stool samples where stirred for 15 seconds six times and at each time point a Kato-Katz slide was prepared and analyzed.Mean hookworm FECs of Kato-Katz slides stored at room temperature steadily decreased following slide preparation. After two hours, mean hookworm FECs decreased from 22 to 16, whereas no reduction was observed if Kato-Katz slides were stored in the refrigerator (19 vs 21). The time x storage interaction effect was statistically significant (coefficient 0.26, 95% CI: 0.17 to 0.35, p < 0.0001). After 24 hours mean hookworm FECs dropped close to zero, irrespective of the storage condition. Whole stool samples stored at room temperature for one day resulted in a mean hookworm FEC decrease of 23% (p < 0.0001), compared to a 13% reduction (p < 0.0001) if samples were stored in the refrigerator. Fecal egg counts of A. lumbricoides and T. trichiura remained stable over time regardless of storage temperature of whole stool samples. Finally, we found a significant reduction of the variation of hookworm and T. trichiura eggs with increasing rounds of stirring the sample, but not for A. lumbricoides. However, for hookworm we observed a simultaneous decrease in mean FECs, making it difficult to draw recommendations on stirring samples.

Conclusions/Significance

Our findings suggest that stool samples (i) should be analyzed on the day of collection and (ii) should be analyzed between 20–30 minutes after slide preparation; when that is not possible, Kato-Katz slides can be stored in a refrigerator up to about 110 minutes.

Burden of depression and anxiety among leprosy affected and associated factors—A cross sectional study from India

PLoS Neglected Tropical Diseases News - 22 January 2021 - 2:00pm

by Karthikeyan Govindasamy, Immanuel Jacob, Raju Moturu Solomon, Joydeepa Darlong

Background

Leprosy is a Neglected Tropical Diseases (NTDs) known to cause stigma and discrimination in low-and middle-income countries. It often results in visible impairments, thus pre-disposing to poor mental health. Aim of the study was to estimate the prevalence of depression and anxiety among people affected by Leprosy and to determine the associated factors.

Methodology/Principal findings

A multi-centric, cross-sectional study was carried out in four leprosy endemic states of India—Chhattisgarh, Maharashtra, West Bengal and Tamil Nadu in randomly selected blocks (a sub-unit of district), from one district in each state. From selected blocks registered for leprosy treatment at public health or referral centres, people above the age of 18 years were interviewed with PHQ-9 and GAD-7 questionnaires for Depression and Anxiety, respectively. Disease profile like leprosy classification, deformity grade, number and site of the patches and socio-economic status were collected along with individual data.Of the total 220 respondents, prevalence of depression and anxiety symptoms was, 33% (73) and 19% (42), respectively. Presence of disability (47%) and Female gender (46%) were significantly associated with depression. Presence of disability (32%), Lower income group (27%) and low education (22%) were significantly associated with symptoms of anxiety. As the severity of disability increased, risk of developing depression and anxiety increased.

Conclusion

The study indicates that more than 30% of people affected by leprosy have mental health problems, which emphasizes the importance of mental health care services in leprosy. Women, those who had lower level of education, those belonging to lower socio-economic status and those with any level of disability due to leprosy are at risk of developing depression and/or anxiety. The study concludes more attention to be paid to the categories identified to be at risk.

Burden of disease and productivity impact of <i>Streptococcus suis</i> infection in Thailand

PLoS Neglected Tropical Diseases News - 22 January 2021 - 2:00pm

by Ajaree Rayanakorn, Zanfina Ademi, Danny Liew, Learn-Han Lee

Background

Streptoccocus suis (S.suis) infection is a neglected zoonosis disease in humans mainly affects men of working age. We estimated the health and economic burden of S.suis infection in Thailand in terms of years of life lost, quality-adjusted life years (QALYs) lost, and productivity-adjusted life years (PALYs) lost which is a novel measure that adjusts years of life lived for productivity loss attributable to disease.

Methods

A decision-analytic Markov model was developed to simulate the impact of S. suis infection and its major complications: death, meningitis and infective endocarditis among Thai people in 2019 with starting age of 51 years. Transition probabilities, and inputs pertaining to costs, utilities and productivity impairment associated with long-term complications were derived from published sources. A lifetime time horizon with follow-up until death or age 100 years was adopted. The simulation was repeated assuming that the cohort had not been infected with S.suis. The differences between the two set of model outputs in years of life, QALYs, and PALYs lived reflected the impact of S.suis infection. An annual discount rate of 3% was applied to both costs and outcomes. One-way sensitivity analyses and Monte Carlo simulation modeling technique using 10,000 iterations were performed to assess the impact of uncertainty in the model.

Key results

This cohort incurred 769 (95% uncertainty interval [UI]: 695 to 841) years of life lost (14% of predicted years of life lived if infection had not occurred), 826 (95% UI: 588 to 1,098) QALYs lost (21%) and 793 (95%UI: 717 to 867) PALYs (15%) lost. These equated to an average of 2.46 years of life, 2.64 QALYs and 2.54 PALYs lost per person. The loss in PALYs was associated with a loss of 346 (95% UI: 240 to 461) million Thai baht (US$11.3 million) in GDP, which equated to 1.1 million Thai baht (US$ 36,033) lost per person.

Conclusions

S.suis infection imposes a significant economic burden both in terms of health and productivity. Further research to investigate the effectiveness of public health awareness programs and disease control interventions should be mandated to provide a clearer picture for decision making in public health strategies and resource allocations.

Genome-wide identification of <i>Aedes albopictus</i> long noncoding RNAs and their association with dengue and Zika virus infection

PLoS Neglected Tropical Diseases News - 22 January 2021 - 2:00pm

by Azali Azlan, Sattam M. Obeidat, Kumitaa Theva Das, Muhammad Amir Yunus, Ghows Azzam

The Asian tiger mosquito, Aedes albopictus (Ae. albopictus), is an important vector that transmits arboviruses such as dengue (DENV), Zika (ZIKV) and Chikungunya virus (CHIKV). Long noncoding RNAs (lncRNAs) are known to regulate various biological processes. Knowledge on Ae. albopictus lncRNAs and their functional role in virus-host interactions are still limited. Here, we identified and characterized the lncRNAs in the genome of an arbovirus vector, Ae. albopictus, and evaluated their potential involvement in DENV and ZIKV infection. We used 148 public datasets, and identified a total of 10, 867 novel lncRNA transcripts, of which 5,809, 4,139, and 919 were intergenic, intronic and antisense respectively. The Ae. albopictus lncRNAs shared many characteristics with other species such as short length, low GC content, and low sequence conservation. RNA-sequencing of Ae. albopictus cells infected with DENV and ZIKV showed that the expression of lncRNAs was altered upon virus infection. Target prediction analysis revealed that Ae. albopictus lncRNAs may regulate the expression of genes involved in immunity and other metabolic and cellular processes. To verify the role of lncRNAs in virus infection, we generated mutations in lncRNA loci using CRISPR-Cas9, and discovered that two lncRNA loci mutations, namely XLOC_029733 (novel lncRNA transcript id: lncRNA_27639.2) and LOC115270134 (known lncRNA transcript id: XR_003899061.1) resulted in enhancement of DENV and ZIKV replication. The results presented here provide an important foundation for future studies of lncRNAs and their relationship with virus infection in Ae. albopictus.

Asymptomatic <i>Leishmania</i> infection in HIV-positive outpatients on antiretroviral therapy in Pernambuco, Brazil

PLoS Neglected Tropical Diseases News - 21 January 2021 - 2:00pm

by Diego Lins Guedes, Alda Maria Justo, Walter Lins Barbosa Júnior, Elis Dionísio da Silva, Samuel Ricarte de Aquino, Manoel Sebastiao da Costa Lima Junior, Ulisses Montarroyos, Gilberto Silva Nunes Bezerra, Amanda Virginia Batista Vieira, Valéria Rêgo Alves Pereira, Zulma Maria de Medeiros

Background

Visceral leishmaniasis (VL) in HIV-positive individuals is a global health problem. HIV-Leishmania coinfection worsens prognosis and mortality risk, and HIV-Leishmania coinfected individuals are more susceptible to VL relapses. Early initiation of antiretroviral therapy can protect against Leishmania infection in individuals living in VL-endemic areas, and regular use of antiretrovirals might prevent VL relapses in these individuals. We conducted a cross-sectional study in Petrolina, Brazil, an VL-endemic area, to estimate the prevalence of asymptomatic Leishmania cases among HIV-positive outpatients.

Methods

We invited any HIV-positive patients, aged ≥ 18-years-old, under antiretroviral therapy, and who were asymptomatic for VL. Patients were tested for Leishmania with enzyme-linked immunosorbent assays (ELISA)-rK39, immunochromatographic test (ICT)-rK39, direct agglutination test (DAT), latex agglutination test (KAtex), and conventional polymerase chain reaction (PCR). HIV-Leishmania coinfection was diagnosed when at least one VL test was positive.

Results

A total of 483 patients were included. The sample was predominantly composed of single, < 48-years-old, black/pardo, heterosexual males, with fewer than 8 years of schooling. The prevalence of asymptomatic HIV-Leishmania coinfection was 9.11% (44/483). HIV mono-infected and HIV-Leishmania coinfected groups differed statistically significantly in terms of race (p = 0.045), marital status (p = 0.030), and HIV viral load (p = 0.046). Black/pardo patients, married patients, and those with an HIV viral load up to 100,000 copies/ml presented higher odds for HIV-Leishmania coinfection.

Conclusions

A considerable number of asymptomatic Leishmania cases were observed among HIV-positive individuals in a VL-endemic area. Given the potential impact on transmission and health costs, as well as the impact on these coinfected individuals, studies of asymptomatic Leishmania carriers can be useful for guiding public health policies in VL-endemic areas aiming to control and eliminate the disease.

Effects of larval rearing substrates on some life-table parameters of <i>Lutzomyia longipalpis</i> sand flies

PLoS Neglected Tropical Diseases News - 21 January 2021 - 2:00pm

by Kelsilandia Aguiar Martins, Maria Helena de Athayde Meirelles, Tiago Feitosa Mota, Ibrahim Abbasi, Artur Trancoso Lopo de Queiroz, Claudia Ida Brodskyn, Patrícia Sampaio Tavares Veras, Deborah Bittencourt Mothé Fraga, Alon Warburg

Sand flies are the insects responsible for transmitting Leishmania parasites, the causative agents of leishmaniasis in humans. However, the effects of sand fly breeding sites on their biology and ecology remain poorly understood. Herein, we studied how larval nutrition associated with putative breeding sites of the sand fly Lutzomyia longipalpis affects their oviposition, development, microbiome, and susceptibility to Leishmania by rearing L. longipalpis on substrates collected from an endemic area for leishmaniasis in Brazil. The results showed that female L. longipalpis select the oviposition site based on its potential to promote larval maturation and while composting cashew leaf litter hindered the development, larvae reared on chicken feces developed rapidly. Typical gut microbial profiles were found in larvae reared upon cashew leaf litter. Adult females from larvae reared on substrate collected in chicken coops were infected with Leishmania infantum, indicating that they were highly susceptible to the parasite. In conclusion, the larval breeding sites can exert an important role in the epidemiology of leishmaniasis.

Leprosy perceptions and knowledge in endemic districts in India and Indonesia: Differences and commonalities

PLoS Neglected Tropical Diseases News - 21 January 2021 - 2:00pm

by Anna Tiny van’t Noordende, Suchitra Lisam, Panca Ruthindartri, Atif Sadiq, Vivek Singh, Miftahol Arifin, Willem Herman van Brakel, Ida J. Korfage

Background

Understanding how knowledge, attitudes and practices regarding leprosy differ in endemic countries can help us develop targeted educational and behavioural change interventions. This study aimed to examine the differences and commonalities in and determinants of knowledge, attitudes, practices and fears regarding leprosy in endemic districts in India and Indonesia.

Principle findings

A cross-sectional mixed-methods design was used. Persons affected by leprosy, their close contacts, community members and health workers were included. Through interview-administered questionnaires we assessed knowledge, attitudes, practices and fears with the KAP measure, EMIC-CSS and SDS. In addition, semi-structured interviews and focus group discussions were conducted. The quantitative data were analysed using stepwise multivariate regression. Determinants of knowledge and stigma that were examined included age, gender, participant type, education, occupation, knowing someone affected by leprosy and district. The qualitative data were analysed using open, inductive coding and content analysis.We administered questionnaires to 2344 participants (46% from India, 54% from Indonesia) as an interview. In addition, 110 participants were interviewed in-depth and 60 participants were included in focus group discussions. Knowledge levels were low in both countries: 88% of the participants in India and 90% of the participants in Indonesia had inadequate knowledge of leprosy. In both countries, cause, mode of transmission, early symptoms and contagiousness of leprosy was least known, and treatment and treatability of leprosy was best known. In both countries, health workers had the highest leprosy knowledge levels and community members the highest stigma levels (a mean score of up to 17.4 on the EMIC-CSS and 9.1 on the SDS). Data from the interviews indicated that people were afraid of being infected by leprosy. Local beliefs and misconceptions differed, for instance that leprosy is in the family for seven generations (Indonesia) or that leprosy is a result of karma (India). The determinants of leprosy knowledge and stigma explained 10–29% of the variability in level of knowledge and 3–10% of the variability in level of stigma.

Conclusion

Our findings show the importance of investigating the perceptions regarding leprosy prior to educational interventions in communities: even though knowledge levels were similar, local beliefs and misconceptions differed per setting. The potential determinants we included in our study explained very little of the variability in level of knowledge and stigma and should be explored further. Detailed knowledge of local knowledge gaps, beliefs and fears can help tailor health education to local circumstances.

Multiplex detection of antibodies to Chikungunya, O’nyong-nyong, Zika, Dengue, West Nile and Usutu viruses in diverse non-human primate species from Cameroon and the Democratic Republic of Congo

PLoS Neglected Tropical Diseases News - 21 January 2021 - 2:00pm

by Raisa Raulino, Guillaume Thaurignac, Christelle Butel, Christian Julian Villabona-Arenas, Thomas Foe, Severin Loul, Simon-Pierre Ndimbo-Kumugo, Placide Mbala-Kingebeni, Sheila Makiala-Mandanda, Steve Ahuka-Mundeke, Karen Kerkhof, Eric Delaporte, Kevin K. Ariën, Vincent Foulongne, Eitel Mpoudi Ngole, Martine Peeters, Ahidjo Ayouba

Background

Epidemic arbovirus transmission occurs among humans by mosquito bites and the sylvatic transmission cycles involving non-human primates (NHPs) still exists. However, limited data are available on the extent in NHPs infections and their role. In this study, we have developed and validated a high-throughput serological screening tool to study the circulation of multiple arboviruses that represent a significant threat to human health, in NHPs in Central Africa.

Methodology/Principal findings

Recombinant proteins NS1, envelope domain-3 (DIII) for the dengue (DENV), yellow fever (YFV), usutu (USUV), west nile (WNV) and zika (ZIKV) and envelope 2 for the chikungunya (CHIKV) and o'nyong-nyong (ONNV) were coupled to Luminex beads to detect IgG directed against these viruses. Evaluation of test performance was made using 161 human sera of known arboviral status (66 negative and 95 positive). The sensitivity and specificity of each antigen were determined by statistical methods and ROC curves (except for ONNV and USUV). All NS1 antigens (except NS1-YFV), CHIKV-E2 and WNV-DIII had sensitivities and specificities > 95%. For the other DIII antigens, the sensitivity was low, limiting the interest of their use for seroprevalence studies. Few simultaneous reactions were observed between the CHIKV+ samples and the NS1 antigens to the non-CHIKV arboviruses. On the other hand, the DENV+ samples crossed-reacted with NS1 of all the DENV serotypes (1 to 4), as well as with ZIKV, USUV and to a lesser extent with YFV. A total of 3,518 samples of 29 species of NHPs from Cameroon and the Democratic Republic of Congo (DRC) were tested against NS1 (except YFV), E2 (CHIKV/ONNV) and DIII (WNV) antigens. In monkeys (n = 2,100), the global prevalence varied between 2 and 5% for the ten antigens tested. When we stratified by monkey’s biotope, the arboreal species showed the highest reactivity. In monkeys from Cameroon, the highest IgG prevalence were observed against ONNV-E2 and DENV2-NS1 with 3.95% and 3.40% respectively and in DRC, ONNV-E2 (6.63%) and WNV-NS1 (4.42%). Overall prevalence was low in apes (n = 1,418): ranging from 0% for USUV-NS1 to 2.6% for CHIKV-E2. However, a very large disparity was observed among collection site and ape species, e.g. 18% (9/40) and 8.2% (4/49) of gorillas were reactive with CHIKV-E2 or WNV-NS1, respectively in two different sites in Cameroon.

Conclusions/Significance

We have developed a serological assay based on Luminex technology, with high specificity and sensitivity for simultaneous detection of antibodies to 10 antigens from 6 different arboviruses. This is the first study that evaluated on a large scale the presence of antibodies to arboviruses in NHPs to evaluate their role in sylvatic cycles. The overall low prevalence (<5%) in more than 3,500 NHPs samples from Cameroon and the DRC does not allow us to affirm that NHP are reservoirs, but rather, intermediate hosts of these viruses.

Drug resistance gene mutations and treatment outcomes in MDR-TB: A prospective study in Eastern China

PLoS Neglected Tropical Diseases News - 20 January 2021 - 2:00pm

by Qiao Liu, Dandan Yang, Beibei Qiu, Leonardo Martinez, Ye Ji, Huan Song, Zhongqi Li, Jianming Wang

Background

Multidrug-resistant tuberculosis (MDR-TB) poses a serious challenge to TB control. It is of great value to search for drug resistance mutation sites and explore the roles that they play in the diagnosis and prognosis of MDR-TB.

Methods

We consecutively enrolled MDR-TB patients from five cities in Jiangsu Province, China, between January 2013 and December 2014. Drug susceptibility tests of rifampin, isoniazid, ofloxacin, and kanamycin were routinely performed by proportion methods on Lowenstein–Jensen (LJ) medium. Drug resistance-related genes were sequenced, and the consistency of genetic mutations and phenotypic resistance was compared. The association between mutations and treatment outcomes was expressed as odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Among 87 MDR-TB patients, 71 with treatment outcomes were involved in the analysis. The proportion of successful treatment was 50.7% (36/71). The rpoB gene exhibited the highest mutation rate (93.0%) followed by katG (70.4%), pncA (33.8%), gyrA (29.6%), eis (15.5%), rrs (12.7%), gyrB (9.9%) and rpsA (4.2%). Multivariable analysis demonstrated that patients with pncA gene mutations (adjusted OR: 19.69; 95% CI: 2.43–159.33), advanced age (adjusted OR: 13.53; 95% CI: 1.46–124.95), and nonstandard treatment (adjusted OR: 7.72; 95% CI: 1.35–44.35) had a significantly higher risk of poor treatment outcomes.

Conclusions

These results suggest that Mycobacterium tuberculosis gene mutations may be related to phenotypic drug susceptibility. The pncA gene mutation along with treatment regimen and age are associated with the treatment outcomes of MDR-TB.

Impaired host resistance to <i>Salmonella</i> during helminth co-infection is restored by anthelmintic treatment prior to bacterial challenge

PLoS Neglected Tropical Diseases News - 20 January 2021 - 2:00pm

by Tara P. Brosschot, Katherine M. Lawrence, Brandon E. Moeller, Mia H. E. Kennedy, Rachael D. FitzPatrick, Courtney M. Gauthier, Dongju Shin, Dominique M. Gatti, Kate M. E. Conway, Lisa A. Reynolds

Intestinal helminth infection can impair host resistance to co-infection with enteric bacterial pathogens. However, it is not known whether helminth drug-clearance can restore host resistance to bacterial infection. Using a mouse helminth-Salmonella co-infection system, we show that anthelmintic treatment prior to Salmonella challenge is sufficient to restore host resistance to Salmonella. The presence of the small intestine-dwelling helminth Heligmosomoides polygyrus at the point of Salmonella infection supports the initial establishment of Salmonella in the small intestinal lumen. Interestingly, if helminth drug-clearance is delayed until Salmonella has already established in the small intestinal lumen, anthelmintic treatment does not result in complete clearance of Salmonella. This suggests that while the presence of helminths supports initial Salmonella colonization, helminths are dispensable for Salmonella persistence in the host small intestine. These data contribute to the mechanistic understanding of how an ongoing or prior helminth infection can affect pathogenic bacterial colonization and persistence in the mammalian intestine.

Correction: Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans

PLoS Neglected Tropical Diseases News - 19 January 2021 - 2:00pm

by Catherine L. Moyes, John Vontas, Ademir J. Martins, Lee Ching Ng, Sin Ying Koou, Isabelle Dusfour, Kamaraju Raghavendra, João Pinto, Vincent Corbel, Jean-Philippe David, David Weetman

The cholera risk assessment in Kano State, Nigeria: A historical review, mapping of hotspots and evaluation of contextual factors

PLoS Neglected Tropical Diseases News - 19 January 2021 - 2:00pm

by Moise Chi Ngwa, Chikwe Ihekweazu, Tochi Okwor, Sebastian Yennan, Nanpring Williams, Kelly Elimian, Nura Yahaya Karaye, Imam Wada Bello, David A. Sack

Nigeria is endemic for cholera since 1970, and Kano State report outbreaks annually with high case fatality ratios ranging from 4.98%/2010 to 5.10%/2018 over the last decade. However, interventions focused on cholera prevention and control have been hampered by a lack of understanding of hotspot Local Government Areas (LGAs) that trigger and sustain yearly outbreaks. The goal of this study was to identify and categorize cholera hotspots in Kano State to inform a national plan for disease control and elimination in the State. We obtained LGA level confirmed and suspected cholera data from 2010 to 2019 from the Nigeria Centre for Disease Control (NCDC) and Kano State Ministry of Health. Data on inland waterbodies and population numbers were obtained from online sources and NCDC, respectively. Clusters (hotspots) were identified using SaTScan through a retrospective analysis of the data for the ten-year period using a Poisson discrete space-time scan statistic. We also used a method newly proposed by the Global Task Force on Cholera Control (GTFCC) to identify and rank hotspots based on two epidemiological indicators including mean annual incidence per 100 000 population of reported cases and the persistence of cholera for the study period. In the ten-year period, 16,461 cholera cases were reported with a case fatality ratio of 3.32% and a mean annual incidence rate of 13.4 cases per 100 000 population. Between 2010 and 2019, the most severe cholera exacerbations occurred in 2014 and 2018 with annual incidence rates of 58.01 and 21.52 cases per 100 000 inhabitants, respectively. Compared to 2017, reported cases and deaths increased by 214.56% and 406.67% in 2018. The geographic distribution of outbreaks revealed considerable spatial heterogeneity with the widest in 2014. Space-time clustering analysis identified 18 out of 44 LGAs as high risk for cholera (hotspots) involving both urban and rural LGAs. Cholera clustered around water bodies, and the relative risk of having cholera inside the hotspot LGA were 1.02 to 3.30 times higher than elsewhere in the State. A total of 4,894,144 inhabitants were in these hotspots LGAs. Of these, six LGAs with a total population of 1.665 million had a relative risk greater than 2 compared to the state as a whole. The SaTScan (statistical) and GTFCC methods were in agreement in hotspots identification. This study identified cholera hotspots LGAs in Kano State from 2010–2019. Hotspots appeared in both urban and rural settings. Focusing control strategies on these hotspots will facilitate control and eliminate cholera from the State.

Factors affecting the uptake of preventive chemotherapy treatment for schistosomiasis in Sub-Saharan Africa: A systematic review

PLoS Neglected Tropical Diseases News - 19 January 2021 - 2:00pm

by Carlos A. Torres-Vitolas, Neerav Dhanani, Fiona M. Fleming

Background

Schistosomiasis affects nearly 220 million people worldwide, mainly in Sub-Saharan Africa (SSA). Preventive chemotherapy (PC) treatment, through regular mass-drug administration (MDA) of Praziquantel tablets remains the control measure of choice by Ministries of Health. Current guidelines recommend that 75% of school-aged children receive treatment. Many programmes, however, struggle to achieve this target. Given the risk of high reinfection rates, attaining sustained high levels of treatment coverage is essential. This study provides a comprehensive review of the barriers and facilitators operating at different levels of analysis, from the individual to the policy level, conditioning the uptake of PC for schistosomiasis in SSA.

Methodology/Principal findings

A systematic literature search was conducted in several databases for publications released between January 2002 and 2019 that examined factors conditioning the uptake of Praziquantel in the context of MDA campaigns in SSA. A total of 2,258 unique abstracts were identified, of which 65 were selected for full text review and 30 met all eligibility criteria. Joanna Briggs Institute’s Critical Appraisal and the Mixed-Methods Assessment tools were used to assess the strength of the evidence. This review was registered with PROSPERO (CRD42017058525).A meta-synthesis approach was used. Results indicated publication bias, with the literature focusing on East African rural settings and evidence at the individual and programmatic levels. The main influencing factors identified included material wellbeing, drug properties, knowledge and attitudes towards schistosomiasis and MDAs, fears of side effects, gender values, community and health systems support, alongside programme design features, like training, sensitisation, and provision of incentives for drug-distributors. The effect of these factors on determining Praziquantel uptake were explored in detail.

Conclusions/Significance

Multiple determinants of treatment uptake were found in each level of analysis examined. Some of them interact with each other, thus affecting outcomes directly and indirectly. The promotion of context-based transdisciplinary research on the complex dynamics of treatment uptake is not only desirable, but essential, to design effective strategies to attain high levels of treatment coverage.

<i>S</i>. <i>mansoni Sm</i>KI-1 Kunitz-domain: Leucine point mutation at P1 site generates enhanced neutrophil elastase inhibitory activity

PLoS Neglected Tropical Diseases News - 19 January 2021 - 2:00pm

by Fábio Mambelli, Bruno P. O. Santos, Suellen B. Morais, Enrico G. T. Gimenez, Duana C. dos S. Astoni, Amanda D. Braga, Rafaela S. Ferreira, Flávio A. Amaral, Mariana T. Q. de Magalhães, Sergio C. Oliveira

The Schistosoma mansoni SmKI-1 protein is composed of two domains: a Kunitz-type serine protease inhibitor motif (KD) and a C-terminus domain with no similarity outside the genera. Our previous work has demonstrated that KD plays an essential role in neutrophil elastase (NE) binding blockage, in neutrophil influx and as a potential anti-inflammatory molecule. In order to enhance NE blocking capacity, we analyzed the KD sequence from a structure-function point of view and designed specific point mutations in order to enhance NE affinity. We substituted the P1 site residue at the reactive site for a leucine (termed RL-KD), given its central role for KD’s inhibition to NE. We have also substituted a glutamic acid that strongly interacts with the P1 residue for an alanine, to help KD to be buried on NE S1 site (termed EA-KD). KD and the mutant proteins were evaluated in silico by molecular docking to human NE, expressed in Escherichia coli and tested towards its NE inhibitory activity. Both mutated proteins presented enhanced NE inhibitory activity in vitro and RL-KD presented the best performance. We further tested RL-KD in vivo in an experimental model of monosodium urate (MSU)-induced acute arthritis. RL-KD showed reduced numbers of total cells and neutrophils in the mouse knee cavity when compared to KD. Nevertheless, both RL-KD and KD reduced mice hypernociception in a similar fashion. In summary, our results demonstrated that both mutated proteins showed enhanced NE inhibitory activity in vitro. However, RL-KD had a prominent effect in diminishing inflammatory parameters in vivo.

Space-time risk cluster of visceral leishmaniasis in Brazilian endemic region with high social vulnerability: An ecological time series study

PLoS Neglected Tropical Diseases News - 19 January 2021 - 2:00pm

by Caique J. N. Ribeiro, Allan D. dos Santos, Shirley V. M. A. Lima, Eliete R. da Silva, Bianca V. S. Ribeiro, Andrezza M. Duque, Marcus V. S. Peixoto, Priscila L. dos Santos, Iris M. de Oliveira, Michael W. Lipscomb, Karina C. G. M. de Araújo, Tatiana R. de Moura

Background

Despite visceral leishmaniasis (VL) being epidemic in most Brazilian regions, the Northeast region is responsible for the highest morbidity and mortality outcomes within the country.

Objective

To analyse the spatiotemporal dynamics of VL cases to identify the temporal trends and high-risk areas for VL transmission, as well as the association of the disease with social vulnerability in Brazilian Northeast.

Methods

We carried out an ecological time series study employing spatial analysis techniques using all VL confirmed cases of 1,794 municipalities of Brazilian Northeast between the years 2000 to 2017. The Social Vulnerability Index (SVI) was used to represent the social vulnerability. Incidence rates were standardized and smoothed by the Local Empirical Bayesian Method. Time trends were examined through segmented linear regression. Spatiotemporal analysis consisted of uni- and bivariate Global and Local Moran indexes and space-time scan statistics.

Results

Incidence rate remained stable and ranged from 4.84 to 3.52 cases/100,000 inhabitants. There was higher case prevalence between males (62.71%), children and adolescents (63.27%), non-white (69.75%) and urban residents (62.58%). Increasing trends of new cases were observed among adult male subjects (≥ 40 years old) and urban residents. Importantly, VL incidence showed a direct spatial dependence. Spatial and space-time clusters were identified in sertão and meio-norte sub-regions, overlapping with high social vulnerability areas.

Conclusions

VL is a persistent health issue in Brazilian Northeast and associated with social vulnerability. Space-time clustering of VL cases in socially vulnerable municipalities demands intersectoral public policies of surveillance and control, with focus on reducing inequalities and improving living conditions for regional inhabitants.

Insecticide-treated house screening protects against Zika-infected <i>Aedes aegypti</i> in Merida, Mexico

PLoS Neglected Tropical Diseases News - 19 January 2021 - 2:00pm

by Pablo Manrique-Saide, Josué Herrera-Bojórquez, Anuar Medina-Barreiro, Emilio Trujillo-Peña, Josué Villegas-Chim, Nina Valadez-González, Ahmed M. M. Ahmed, Hugo Delfín-González, Jorge Palacio-Vargas, Azael Che-Mendoza, Norma Pavía-Ruz, Adriana E. Flores, Gonzalo Vazquez-Prokopec

Background

The integration of house-screening and long-lasting insecticidal nets, known as insecticide-treated screening (ITS), can provide simple, safe, and low-tech Aedes aegypti control. Cluster randomised controlled trials in two endemic localities for Ae. aegypti of south Mexico, showed that ITS conferred both, immediate and sustained (~2 yr) impact on indoor-female Ae. aegypti infestations. Such encouraging results require further validation with studies quantifying more epidemiologically-related endpoints, including arbovirus infection in Ae. aegypti. We evaluated the efficacy of protecting houses with ITS on Ae. aegypti infestation and arbovirus infection during a Zika outbreak in Merida, Yucatan, Mexico.

Methodology/Principal findings

A two-arm cluster-randomised controlled trial evaluated the entomological efficacy of ITS compared to the absence of ITS (with both arms able to receive routine arbovirus vector control) in the neighbourhood Juan Pablo II of Merida. Cross-sectional entomological surveys quantified indoor adult mosquito infestation and arbovirus infection at baseline (pre-ITS installation) and throughout two post-intervention (PI) surveys spaced at 6-month intervals corresponding to dry/rainy seasons over one year (2016–2017). Household-surveys assessed the social reception of the intervention. Houses with ITS were 79–85% less infested with Aedes females than control houses up to one-year PI. A similar significant trend was observed for blood-fed Ae. aegypti females (76–82%). Houses with ITS had significantly less infected female Ae. aegypti than controls during the peak of the epidemic (OR = 0.15, 95%CI: 0.08–0.29), an effect that was significant up to a year PI (OR = 0.24, 0.15–0.39). Communities strongly accepted the intervention, due to its perceived mode of action, the prevalent risk for Aedes-borne diseases in the area, and the positive feedback from neighbours receiving ITS.

Conclusions/Significance

We show evidence of the protective efficacy of ITS against an arboviral disease of major relevance, and discuss the relevance of our findings for intervention adoption.

Sociodemographic predictors of knowledge, mosquito bite patterns and protective behaviors concerning vector borne disease: The case of dengue fever in Chinese subtropical city, Hong Kong

PLoS Neglected Tropical Diseases News - 19 January 2021 - 2:00pm

by Emily Ying Yang Chan, Eugene Siu Kai Lo, Zhe Huang, Holly Ching Yu Lam, May Pui-shan Yeung, Kin-on Kwok, Kevin Kei Ching Hung, Shelly Lap-ah Tse

Geographic pattern of dengue fever is changing due to the global environmental and climate changes in the 21st century. Evidence of community’s knowledge, mosquito bite patterns and protective behavior practices in non-endemic regions is limited. This study examined the knowledge of dengue, mosquito bite patterns, protective behavior practices and their associated factors in Hong Kong, a non-endemic subtropical city. A population-based random telephone survey (n = 590) was conducted three weeks after the government announcement of a local dengue outbreak in August 2018. Sociodemographic status, awareness, knowledge, protective measures, bite patterns of mosquito were collected. Results indicated high level of community awareness of the local outbreak (95.2%), symptom identification (84.0%) and adoption of at least one mosquito protective measures (nearly 80%). About 40% of respondents reported that they were bitten by mosquitoes during the study period, a high mosquito season in Hong Kong. Mosquito bites were prevalent near grassy area (63.4%), at home (42.6%) and at public transportation waiting spots (39.6%). Younger people (< 25 years old), female, those who lived on lower floors (≤the 6th) and near grassy area were at higher risk of mosquito bites at home. Respondents perceived higher threat of dengue to society were more likely to practice mosquito prevention. While residential factors affected their indoor prevention, other socio-demographic factors affected the outdoor prevention. Practicing prevention behaviors were associated with self-reported mosquito bite at home. Furthermore, the general prevention uptake rate unchanged after the announcement of local dengue outbreak. Although the uptake rate of protective measures during August was high, 40% participants reported they were bitten. Also public locations are more common area for bites. which suggested stronger mosquito prevention and control on public environments and more personal protective behaviors should be advocated.

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