PLOS Neglected Tropical Diseases

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ISSN / EISSN : 1935-2735 / 1935-2735
Current Publisher: Public Library of Science (PLoS) (10.1371)
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Emmanuel Echeverry-Cárdenas, Carolina López-Castañeda, ,
PLOS Neglected Tropical Diseases, Volume 15; doi:10.1371/journal.pntd.0008212

Abstract:
In Colombia, little is known on the distribution of the Asian mosquito Aedes albopictus, main vector of dengue, chikungunya, and Zika in Asia and Oceania. Therefore, this work sought to estimate its current and future potential geographic distribution under the Representative Concentration Paths (RCP) 2.6 and 8.5 emission scenarios by 2050 and 2070, using ecological niche models. For this, predictions were made in MaxEnt, employing occurrences of A. albopictus from their native area and South America and bioclimatic variables of these places. We found that, from their invasion of Colombia to the most recent years, A. albopictus is present in 47% of the country, in peri-urban (20%), rural (23%), and urban (57%) areas between 0 and 1800 m, with Antioquia and Valle del Cauca being the departments with most of the records. Our ecological niche modelling for the currently suggests that A. albopictus is distributed in 96% of the Colombian continental surface up to 3000 m (p < 0.001) putting at risk at least 48 million of people that could be infected by the arboviruses that this species transmits. Additionally, by 2050 and 2070, under RCP 2.6 scenario, its distribution could cover to nearly 90% of continental extension up to 3100 m (≈55 million of people at risk), while under RCP 8.5 scenario, it could decrease below 60% of continental extension, but expand upward to 3200 m (< 38 million of people at risk). These results suggest that, currently in Colombia, A. albopictus is found throughout the country and climate change could diminish eventually its area of distribution, but increase its altitudinal range. In Colombia, surveillance and vector control programs must focus their attention on this vector to avoid complications in the national public health setting.
Daoxiu Xu, Xue Bai, Jing Xu, , Zijian Dong, Wenjie Shi, Fengyan Xu, Yanfeng Li, Mingyuan Liu,
PLOS Neglected Tropical Diseases, Volume 15; doi:10.1371/journal.pntd.0009408

Abstract:
Trichinellosis is a major foodborne parasitosis caused by Trichinella spiralis. In the present study, a serine protease gene from an adult T. spiralis (Ts-Adsp) cDNA library was cloned, expressed in Escherichia coli and purified by Ni-affinity chromatography. Previous studies of our laboratory have found that mice vaccinated with recombinant Ts-Adsp protein (rTs-Adsp) exhibited partial protection against T. spiralis infection. In this study, the protective effect of rTs-Adsp against T. spiralis infection in pigs was further explored. The cell-mediated and humoral immune responses induced by rTs-Adsp were measured, including the dynamic trends of specific antibody levels (IgG, IgG1, IgG2a and IgM), as well as the levels of cytokines (IFN-γ, IL-2, IL-4, and IL-10) in the serum. Moreover, the changes in T lymphocytes, B lymphocytes, and neutrophils were measured to evaluate cellular immune responses in pigs vaccinated with rTs-Adsp. The results indicated that a Th1-Th2 mixed immune response with Th1 predominant was induced by rTs-Adsp after vaccination. Flow cytometric analysis showed that the proportions of CD4+ T cells, B cells, and neutrophils in the immunized groups were significantly increased. Furthermore, pigs vaccinated with rTs-Adsp exhibited a 50.9% reduction in the muscle larvae burden, compare with pigs from the PBS group five weeks after challenged. Our results suggested that rTs-Adsp elicited partial protection and it could be a potential target molecule for preventing and controlling Trichinella transmission from pigs to human.
, , Donatien Moukassa, Michel Develoux,
PLOS Neglected Tropical Diseases, Volume 15; doi:10.1371/journal.pntd.0009318

Abstract:
The Republic of Congo (RoC) is one of the African countries with the most histoplasmosis cases reported. This review summarizes the current status regarding epidemiology, diagnostic tools, and treatment of histoplasmosis in the RoC. A computerized search was performed from online databases Medline, PubMed, HINARI, and Google Scholar to collect literature on histoplasmosis in the RoC. We found 57 cases of histoplasmosis diagnosed between 1954 and 2019, corresponding to an incidence rate of 1–3 cases each year without significant impact of the AIDS epidemic in the country. Of the 57 cases, 54 (94.7%) were cases of Histoplasma capsulatum var. duboisii (Hcd) infection, African histoplasmosis. Three cases (5.3%) of Histoplasma capsulatum var. capsulatum infection were recorded, but all were acquired outside in the RoC. The patients’ ages ranged between 13 months to 60 years. An equal number of cases were observed in adults in the third or fourth decades (n = 14; 24.6%) and in children aged ≤15 years. Skin lesions (46.3%), lymph nodes (37%), and bone lesions (26%) were the most frequent clinical presentations. Most diagnoses were based on histopathology and distinctive large yeast forms seen in tissue. Amphotericin B (AmB) was first line therapy in 65% of the cases and itraconazole (25%) for maintenance therapy. The occurrence of African histoplasmosis in apparently normal children raises the possibility that African histoplasmosis is linked to environmental fungal exposure.
PLOS Neglected Tropical Diseases, Volume 15; doi:10.1371/journal.pntd.0009363

Abstract:
Species usually develop reproductive isolation mechanisms allowing them to avoid interbreeding. These preventive barriers can act before reproduction, “pre-zygotic barriers”, or after reproduction, “post-zygotic barriers”. Pre-zygotic barriers prevent unfavourable mating, while post-zygotic barriers determine the viability and selective success of the hybrid offspring. Hybridization in parasites and the underlying reproductive isolation mechanisms maintaining their genetic integrity have been overlooked. Using an integrated approach this work aims to quantify the relative importance of pre-zygotic barriers in Schistosoma haematobium x S. bovis crosses. These two co-endemic species cause schistosomiasis, one of the major debilitating parasitic diseases worldwide, and can hybridize naturally. Using mate choice experiments we first tested if a specific mate recognition system exists between both species. Second, using RNA-sequencing we analysed differential gene expression between homo- and hetero-specific pairing in male and female adult parasites. We show that homo- and hetero-specific pairing occurs randomly between these two species, and few genes in both sexes are affected by hetero-specific pairing. This suggests that i) mate choice is not a reproductive isolating factor, and that ii) no pre-zygotic barrier except spatial isolation “by the final vertebrate host” seems to limit interbreeding between these two species. Interestingly, among the few genes affected by the pairing status of the worms, some can be related to pathways affected during male and female interactions and may also present interesting candidates for species isolation mechanisms and hybridization in schistosome parasites.
José A. C. Nery, Anna M. Sales, Mariana A. V. B. Hacker, , Raquel C. Maia, Euzenir N. Sarno,
PLOS Neglected Tropical Diseases, Volume 15; doi:10.1371/journal.pntd.0009382

Abstract:
The World Health Organization has raised concerns about the increasing number of Hansen disease (HD) relapses worldwide, especially in Brazil, India, and Indonesia that report the highest number of recurrent cases. Relapses are an indicator of MDT effectiveness and can reflect Mycobacterium leprae persistence or re-infection. Relapse is also a potential marker for the development or progression of disability. In this research, we studied a large cohort of persons affected by HD treated with full fixed-dose multibacillary (MB) multidrug therapy (MDT) followed for up to 20 years and observed that relapses are a rare event. We estimated the incidence density of relapse in a cohort of patients classified to receive MB regime (bacillary index (BI) > 0), diagnosed between September 1997 and June 2017, and treated with twelve-dose MB-MDT at a HD reference center in Rio de Janeiro, Brazil. We obtained the data from the data management system of the clinic routine service. We linked the selected cases to the dataset of relapses of the national HD data to confirm possible relapse cases diagnosed elsewhere. We diagnosed ten cases of relapse in a cohort of 713 patients followed-up for a mean of 12.1 years. This resulted in an incidence rate of 1.16 relapse cases per 1000 person-year (95% CI = 0.5915–2.076). The accumulated risk was 0.025 in 20 years. The very low risk observed in this cohort of twelve-dose-treated MB patients reinforces the success of the current MDT scheme.
, Raman Velayudhan,
PLOS Neglected Tropical Diseases, Volume 15; doi:10.1371/journal.pntd.0009358

Abstract:
Interventions to control the vectors of human diseases, notably malaria, leishmaniasis and dengue, have relied mainly on the action of chemical insecticides. However, concerns have been raised regarding the management of insecticides in vector-borne disease-endemic countries. Our study aimed to analyze how vector control insecticides are managed in selected countries to extract lessons learned. A qualitative analysis of the situation of vector control insecticides management was conducted in six countries. Multi-stakeholder meetings and key informer interviews were conducted on aspects covering the pesticide lifecycle. Findings were compared and synthesized to extract lessons learned. Centrally executed guidelines and standards on the management of insecticides offered direction and control in most malaria programs, but were largely lacking from decentralized dengue programs, where practices of procurement, application, safety, storage, and disposal were variable between districts. Decentralized programs were better at facilitating participation of stakeholders and local communities and securing financing from local budgets. However, little coordination existed between malaria, visceral leishmaniasis and dengue programs within countries. Entomological capacity was concentrated in malaria programs at central level, while dengue and visceral leishmaniasis programs were missing out on expertise. Monitoring systems for insecticide resistance in malaria vectors were rarely used for dengue or visceral leishmaniasis vectors. Strategies for insecticide resistance management, where present, did not extend across programs or sectors in most countries. Dengue programs in most countries continued to rely on space spraying which, considering the realities on the ground, call for revision of international guidelines. Vector control programs in the selected countries were confronted with critical shortcomings in the procurement, application, safety measures, storage, and disposal of vector control insecticides, with implications for the efficiency, effectiveness, and safety of vector control. Further international support is needed to assist countries in situation analysis, action planning and development of national guidelines on vector control insecticide management.
Bhavneet Walia, , Sandra D. Lane, Timothy Endy, Antonio Montresor,
PLOS Neglected Tropical Diseases, Volume 15; doi:10.1371/journal.pntd.0009282

Abstract:
Background Soil transmitted helminths (STH) are a common infection among pregnant women in areas with poor access to sanitation. Deworming medications are cheap and safe; however, the health benefit of deworming during pregnancy is not clear. Methods / Principal findings We created a retrospective cohort of more than 800,000 births from 95 Demographic and Health Survey datasets to estimate the impact of deworming medicine during routine antenatal care (ANC) on neonatal mortality and low birthweight. We first matched births on the probability of receiving deworming during ANC. We then modeled the birth outcomes with the matched group as a random intercept to estimate the effect of deworming during antenatal care after accounting for various risk factors. We also tested for effect modification of soil transmitted helminth prevalence on the impact of deworming during ANC. Receipt of deworming medication during ANC was associated with a 14% reduction in the risk of neonatal mortality (95% confidence interval = 10–17%, n = 797,772 births), with no difference between high and low transmission countries. In low transmission countries, we found an 11% reduction in the odds of low birth weight (95% confidence interval = 8–13%) for women receiving deworming medicine, and in high transmission countries, we found a 2% reduction in the odds of low birthweight (95% confidence interval = 0–5%). Conclusions / Significance These results suggest a substantial health benefit for deworming during ANC that may be even greater in countries with low STH transmission.
, Elisabeth Astrup, Kari Otterdal, Tove Lekva, Jeshina Janardhanan, John A. J. Prakash, Kurien Thomas, Annika E. Michelsen, Pål Aukrust, , et al.
PLOS Neglected Tropical Diseases, Volume 15; doi:10.1371/journal.pntd.0009185

Abstract:
Background The mechanisms that control local and systemic inflammation in scrub typhus have only been partially elucidated. The wingless (Wnt) signaling pathways are emerging as important regulators of inflammation and infection, but have not been investigated in scrub typhus. Methodology/Principal findings Plasma levels of secreted Wnt antagonists (i.e. DKK-1, sFRP-3, WIF-1 and SOST) were analyzed in patients with scrub typhus (n = 129), patients with similar febrile illness without O. tsutsugamushi infection (n = 31), febrile infectious disease controls, and in healthy controls (n = 31) from the same area of South India, and were correlated to markers of inflammation, immune and endothelial cell activation as well as for their association with organ specific dysfunction and mortality in these patients. We found i) Levels of SOST and in particular sFRP-3 and WIF-1 were markedly increased and DKK-1 decreased in scrub typhus patients at admission to the hospital compared to healthy controls. ii) In recovering scrub typhus patients, SOST, sFRP-3 and WIF-1 decreased and DKK-1 increased. iii) SOST was positively correlated with markers of monocyte/macrophage and endothelial/vascular activation as well as with renal dysfunction and poor outcome iv) Finally, regulation of Wnt pathways by O. tsutsugamushi in vitro in monocytes and ex vivo in mononuclear cells isolated from patients with scrub typhus, as evaluated by gene expression studies available in public repositories, revealed markedly attenuated canonical Wnt signaling. Conclusions/Significance Our findings suggest that scrub typhus is characterized by attenuated Wnt signaling possibly involving dysregulated levels of several secreted pathway antagonists. The secreted Wnt antagonist SOST was strongly associated with renal dysfunction and poor prognosis in these patients.
, André Barateiro, Erika Paula Machado Peixoto, André Boler Cláudio da Silva Barros, , , , , , Giuseppe Palmisano, et al.
PLOS Neglected Tropical Diseases, Volume 15; doi:10.1371/journal.pntd.0009390

Abstract:
Background Malaria in Brazil represents one of the highest percentages of Latin America cases, where approximately 84% of infections are attributed to Plasmodium (P.) vivax. Despite the high incidence, many aspects of gestational malaria resulting from P. vivax infections remain poorly studied. As such, we aimed to evaluate the consequences of P. vivax infections during gestation on the health of mothers and their neonates in an endemic area of the Amazon. Methods and findings We have conducted an observational cohort study in Brazilian Amazon between January 2013 and April 2015. 600 pregnant women were enrolled and followed until delivery. After applying exclusion criteria, 329 mother-child pairs were included in the analysis. Clinical data regarding maternal infection, newborn’s anthropometric measures, placental histopathological characteristics, and angiogenic and inflammatory factors were evaluated. The presence of plasma IgG against the P. vivax (Pv) MSP119 protein was used as marker of exposure and possible associations with pregnancy outcomes were analyzed. Multivariate logistic regression analysis revealed that P. vivax infections during the first trimester of pregnancy are associated with adverse gestational outcomes such as premature birth (adjusted odds ratio [aOR] 8.12, 95% confidence interval [95%CI] 2.69–24.54, p < 0.0001) and reduced head circumference (aOR 3.58, 95%CI 1.29–9.97, p = 0.01). Histopathology analysis showed marked differences between placentas from P. vivax-infected and non-infected pregnant women, especially regarding placental monocytes infiltrate. Placental levels of vasomodulatory factors such as angiopoietin-2 (ANG-2) and complement proteins such as C5a were also altered at delivery. Plasma levels of anti-PvMSP119 IgG in infected pregnant women were shown to be a reliable exposure marker; yet, with no association with improved pregnancy outcomes. Conclusions This study indicates that P. vivax malaria during the first trimester of pregnancy represents a higher likelihood of subsequent poor pregnancy outcomes associated with marked placental histologic modification and angiogenic/inflammatory imbalance. Additionally, our findings support the idea that antibodies against PvMSP119 are not protective against poor pregnancy outcomes induced by P. vivax infections.
PLOS Neglected Tropical Diseases, Volume 15; doi:10.1371/journal.pntd.0009370

Abstract:
Background The diagnosis of cystic echinococcosis (CE) is primarily based on imaging, while serology should be applied when imaging is inconclusive. CE cyst stage has been reported among the most important factors influencing the outcome of serodiagnosis. We performed a systematic review and meta-analysis of the relation between cyst stage of hepatic CE and diagnostic sensitivity of serological tests, to evaluate whether their relation is a consistent finding and provide guidance for the interpretation of results of serological tests. Methodology/Principal findings MEDLINE, EMBASE, CENTRAL, and Lilacs databases were searched on December 1st 2019. Original studies published after 2003 (year of publication of the CE cyst classification), reporting sensitivity of serological tests applied to the diagnosis of human hepatic CE, as diagnosed and staged by imaging, were included. The quality of studies was assessed using the Newcastle-Ottawa Scale. Data from 14 studies were included in the meta-analysis. Summary estimates of sensitivities and 95% confidence intervals were obtained using random effects meta-analysis. Overall, test sensitivity was highest in the presence of CE2 and CE3 (CE3a and/or CE3b), and lowest in the presence of CE5 and CE4 cysts. ELISA, ICT and WB showed the highest sensitivities, while IHA performed worst. Conclusions/Significance The results of our study confirm the presence of a clear and consistent relation between cyst stage and serological tests results. Limitations of evidence included the heterogeneity of the antigenic preparations used, which prevented to determine whether the relation between cyst stage and sensitivity was influenced by the type of antigenic preparation, the paucity of studies testing the same panel of sera with different assays, and the lack of studies assessing the performance of the same assay in both field and hospital-based settings. Our results indicate the absolute need to consider cyst staging when evaluating serological results of patients with hepatic CE.
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