PLoS Neglected Tropical Diseases最新文献

Fungal diseases are associated with high morbidity and mortality, yet their epidemiology and burden are not well addressed. While deaths probably exceed 1.5 million per year, many cases remain undiagnosed and underreported. Estimating the burden of these diseases is needed for prioritization and implementation of effective control programs. Here we used a model based on population at risk to estimate the burden of serious fungal infections in Sudan. The prevalence of the susceptible population including HIV, TB, cancer, asthma, and COPD was obtained from the literature. Incidence and prevalence of fungal infections were calculated using local data when applicable and if not available then regional or international figures were used. In total, the estimated number of Sudanese suffering from fungal disease is 5 M (10% of the total population). Tinea capitis, recurrent vulvovaginitis and keratitis are estimated to affect 4,127,760, 631,261, and 6,552 patients, respectively. HIV-related mycosis is estimated to affect 5,945 oral candidiasis, 1,921 esophageal candidiasis, 571 Pneumocystis pneumonia, and 462 cryptococcal meningitis cases. Aspergillus infections are estimated as follow: 3,438 invasive aspergillosis, 14,950 chronic pulmonary aspergillosis, 67,860 allergic bronchopulmonary aspergillosis cases, while the prevalence of severe asthma with fungal sensitization and fungal rhinosinusitis was 86,860 and 93,600 cases, respectively. The neglected tropical disease eumycetoma was estimated to affect 16,837 cases with a rate of 36/100,000. Serious fungal infections are quite common in Sudan and require urgent attention to improve diagnosis, promote treatment, and develop surveillance programs.

[This corrects the article DOI: 10.1371/journal.pntd.0011429.].

Dengue virus (DENV) transmission from humans to mosquitoes is a poorly documented, but critical component of DENV epidemiology. Magnitude of viremia is the primary determinant of successful human-to-mosquito DENV transmission. People with the same level of viremia, however, can vary in their infectiousness to mosquitoes as a function of other factors that remain to be elucidated. Here, we report on a field-based study in the city of Iquitos, Peru, where we conducted direct mosquito feedings on people naturally infected with DENV and that experienced mild illness. We also enrolled people naturally infected with Zika virus (ZIKV) after the introduction of ZIKV in Iquitos during the study period. Of the 54 study participants involved in direct mosquito feedings, 43 were infected with DENV-2, two with DENV-3, and nine with ZIKV. Our analysis excluded participants whose viremia was detectable at enrollment but undetectable at the time of mosquito feeding, which was the case for all participants with DENV-3 and ZIKV infections. We analyzed the probability of onward transmission during 50 feeding events involving 27 participants infected with DENV-2 based on the presence of infectious virus in mosquito saliva 7-16 days post blood meal. Transmission probability was positively associated with the level of viremia and duration of extrinsic incubation in the mosquito. In addition, transmission probability was influenced by the day of illness in a non-monotonic fashion; i.e., transmission probability increased until 2 days after symptom onset and decreased thereafter. We conclude that mildly ill DENV-infected humans with similar levels of viremia during the first two days after symptom onset will be most infectious to mosquitoes on the second day of their illness. Quantifying variation within and between people in their contribution to DENV transmission is essential to better understand the biological determinants of human infectiousness, parametrize epidemiological models, and improve disease surveillance and prevention strategies.

Iron is a trace metal element that is essential for the survival of cells and parasites. The role of iron in cerebral toxoplasmosis (CT) is still unclear. Deferiprone (DFP) is the orally active iron chelator that binds iron in a molar ratio of 3:1 (ligand:iron) and promotes urinary iron excretion to remove excess iron from the body. The aims of this experiment were to observe the alterations in iron in brains with Toxoplasma gondii (T. gondii) acute infections and to investigate the mechanism of ferroptosis in CT using DFP. We established a cerebral toxoplasmosis model in vivo using TgCtwh3, the dominant strains of which are prevalent in China, and treated the mice with DFP at a dose of 75 mg/kg/d. Meanwhile, we treated the HT-22 cells with 100 μM DFP for half an hour and then infected cells with TgCtwh3 in vitro. A qRT-PCR assay of TgSAG1 levels showed a response to the T. gondii burden. We used inductively coupled plasma mass spectrometry, an iron ion assay kit, Western blot analysis, glutathione and glutathione disulfide assay kits, a malonaldehyde assay kit, and immunofluorescence to detect the ferroptosis-related indexes in the mouse hippocampus and HT-22 cells. The inflammatory factors interferon-γ, tumor necrosis factor-α, transforming growth factor-β, and arginase 1 in the hippocampus and cells were detected using the Western blot assay. Hematoxylin and eosin staining, electron microscopy, and the Morris water maze experiment were used to evaluate the brain injuries of the mice. The results showed that TgCtwh3 infection is followed by the activation of ferroptosis-related signaling pathways and hippocampal pathological damage in mice. The use of DFP led to ferroptosis resistance and attenuated pathological changes, inflammatory reactions and T. gondii burden of the mice, prolonging their survival time. The HT-22 cells with TgCtwh3 activated the ferroptosis pathway and was inhibit by DFP in vitro. In TgCtwh3-infected cells, inflammatory response and mitochondrial damage were severe, but these effects could be reduced by DFP. Our study elucidates the mechanism by which T. gondii interferes with the host's iron metabolism and activates ferroptosis, complementing the pathogenic mechanism of CT and further demonstrating the potential value of DFP for the treatment of CT.

Background: After the unprecedented Zika virus (ZIKV) outbreak in the western hemisphere from 2015-2018, Aedes aegypti and Ae. albopictus are now well established primary and secondary ZIKV vectors, respectively. Consensus about identification and importance of other secondary ZIKV vectors remain. This systematic review aims to provide a list of vector species capable of transmitting ZIKV by reviewing evidence from laboratory vector competence (VC) studies and to identify key knowledge gaps and issues within the ZIKV VC literature.

Methods: A search was performed until 15th March 2022 on the Cochrane Library, Lilacs, PubMed, Web of Science, WHOLIS and Google Scholar. The search strings included three general categories: 1) "ZIKA"; 2) "vector"; 3) "competence", "transmission", "isolation", or "feeding behavior" and their combinations. Inclusion and exclusion criteria has been predefined and quality of included articles was assessed by STROBE and STROME-ID criteria.

Findings: From 8,986 articles retrieved, 2,349 non-duplicates were screened by title and abstracts,103 evaluated using the full text, and 45 included in this analysis. Main findings are 1) secondary vectors of interest include Ae. japonicus, Ae. detritus, and Ae. vexans at higher temperature 2) Culex quinquefasciatus was not found to be a competent vector of ZIKV, 3) considerable heterogeneity in VC, depending on the local mosquito strain and virus used in testing was observed. Critical issues or gaps identified included 1) inconsistent definitions of VC parameters across the literature; 2) equivalency of using different mosquito body parts to evaluate VC parameters for infection (mosquito bodies versus midguts), dissemination (heads, legs or wings versus salivary glands), and transmission (detection or virus amplification in saliva, FTA cards, transmission to neonatal mice); 3) articles that fail to use infectious virus assays to confirm the presence of live virus; 4) need for more studies using murine models with immunocompromised mice to infect mosquitoes.

Conclusion: Recent, large collaborative multi-country projects to conduct large scale evaluations of specific mosquito species represent the most appropriate approach to establish VC of mosquito species.

Background: The order Rickettsiales contains a group of vector-borne gram-negative obligate intracellular bacteria, which often cause human emerging infectious diseases and economic losses for dairy and meat industries. The purpose of this study is to investigate the distribution of the pathogens including Rickettsia spp., Anaplasma spp., and Ehrlichia spp. in the order Rickettsiales in ticks from Yueyang, a prefecture-level city of Hunan Province in Sothern China, and assess the potentiality of transovarial transmission of these rickettsial organisms.

Methods: Ticks were collected from cattle in a farm in Yueyang City and the tick DNA was used as template to amplify the htrA, rrs, gltA, ompA and ompB genes of Rickettsia as well as rrs and groEL genes of Anaplasma and Ehrlichia.

Results: All ticks (465) collected were the cattle tick, Rhipicephalus microplus. PCR showed the minimum infection rate (MIR) was 1.5% (7/465) for Candidatus Rickettsia xinyangensis, 1.9% (9/465) for C. Anaplasma boleense, 1.3% (6/465) for Anaplasma platys, 0.6% (3/465) for A. marginale, and 1.17% (2/465) for each of A. bovis, Ehrlichia minasensis, and a non-classified Ehrlichia sp. A human pathogen, C. Rickettsia xinyangensis and A. platys were detected in 100% (3/3) and 33.3% (2/6) laboratory-hatched larval pools from infected females respectively.

Conclusion: Our study revealed a diversity of pathogenic rickettsial species in R. microplus ticks from Hunan Province suggesting a threat to people and animals in China. This study also provided the first molecular evidence for the potential transovarial transmission of C. Rickettsia xinyangensis and A. platys in R. microplus, indicating that R. microplus may act as the host of these two pathogens.

Background: Podoconiosis is one of the neglected tropical diseases (NTD) with the greatest potential for elimination. Despite its public health importance, podoconiosis is a poorly understood disease which led to a widespread misconception about its cause, prevention, and treatment. Even though the exact global burden is still to be measured, it is estimated that at least 4 million people are affected with podoconiosis worldwide, of which more than 1.5 million people are in Ethiopia. The objective of this study was to identify the determinants of podoconiosis in Bensa District, Sidama Regional State, Ethiopia.

Methodology/principal findings: A community-based unmatched case-control study was used to identify the determinants of podoconiosis. The sample size was estimated using the double population proportion formula. An interviewer-administered structured questionnaire was used for data collection. Blood specimens collected from cases were tested by Filariasis Test Strip to exclude lymphatic filariasis. Data were checked for completeness, coded and entered into Epi-data Version 4.6, and exported to the SPSS version 22 software. Variables with a p<0.2 in the bivariate analysis were further analyzed using multivariable binary logistic regression. Multivariable logistic regression analysis was used to examine determinants that could be associated with podoconiosis with a 95% confidence interval. A total of 459 (153 cases and 306 controls) participants were included with a response rate of 100%. Factors such as the age of participant [AOR = 0.34, 95% CI (0.13-0.87)], being female [AOR = 2.90, 95% CI (1.40-6.10)], age at which shoe wearing started [AOR = 0.7, 95% CI (0.03-0.16)], not wearing shoe daily [AOR = 2.26, 95% CI (1.05-4.86)], wearing hard plastic shoe [AOR = 3.38, 95% CI (1.31-10.89)], and family history with a similar disease (leg swelling) [AOR = 10.2, 95% CI (3.97-26.37)] were significantly associated with the occurrence of podoconiosis.

Conclusions/significance: The age of the participants, gender, the age at which shoe wearing started, type of shoe the participants' wear, frequency of shoe wearing, traveling barefoot, and family history with similar disease (leg swelling) were significantly associated with the occurrence of podoconiosis. Sidama regional health bureau along with non-governmental organizations working on the neglected tropical disease should plan modalities on awareness creation and comprehensive health education on shoe wearing and foot hygiene.

Background: Onchocerciasis affects the quality of life to a greater extent among affected individuals. The World Health Organization (WHO)'s Onchocerciasis Control Program (OCP) has effectively reduced the prevalence of onchocerciasis by interrupting the transmission of the parasite and by mass population treatment in the regions at risk of the disease. Despite the successful reduction of the prevalence of onchocerciasis by WHO, the socioeconomic burden resulting from the disabilities caused by onchocerciasis are still immense. This study sought to explore the adolescents' perception regarding the management of onchocerciasis, community and health system support in Nkwanta North District of Ghana.

Method: This study adopted a qualitative phenomenological design and exploratory, descriptive qualitative approach. An in-depth interview guide was developed to collect data for the study. One-on-one interview was conducted. Data collected from 16 onchocerciasis adolescent patients were analysed thematically using ATLAS.ti v7.5.7. Quotes from the participants were presented verbatim to substantiate the themes realised.

Results: Most of the 12 participants (75.0%) were aged 15-18 years old. It was noted that 6(37.50%) of participants were in Junior High School (JHS), while 4(25.0%) were in Senior High School (SHS). It was noted that community members have diverse understandings and perceptions of onchocerciasis, including beliefs that Onchocerciasis is a serious disease that can cause blindness; it is caused by the consumption of some types of food products or stressful work. Adolescents believed that onchocerciasis was caused by insect bite blood infection, poor environmental hygiene, sun or could have been inherited from parents. Ivermectin treatment was noted by adolescents to have helped relieve the symptoms of ochocerciasis they were experiencing. However, the adolescents indicated that they had experienced some side effects, including fever, headache, body itching, rushes, swollen body and blurred vision from the drug.

Conclusion: Inadequate education and communication about onchocerciasis resulted in diverse and erroneous meanings of onchocerciasis among community members. Our research recognises that community and health system supports is very important in the effective management of Onchocerciasis, contributing to the attainment of Sustainable Development Goal (SDG) 3.3, which is targeted at ending the epidemic of NTDs like onchocerciasis by 2030.

Background: There is a lack of systematic evidence for strategies to control loiasis transmission in highly endemic regions. Here we assessed albendazole and ivermectin based treatment regimens to reduce Loa loa microfilaraemia in Gabon.

Methods: Eligible adult patients with L. loa microfilaraemia between 5,000 and 50,000 microfilariae/ml were randomized to either a control or one of three intervention groups (1:2:2:2 allocation ratio) consisting of three-week twice daily 400mg oral albendazole followed by 1) no treatment, 2) two further weeks of twice daily 400mg albendazole, or 3) a single dose of ivermectin in this open label randomized assessor blinded controlled clinical trial. The primary outcome was the proportion of participants with L. loa microfilaraemia ≤ 100 mf/ml at Day 168.

Results: In the efficacy-population of 42 patients 0 (0%; control group), 1 (9%; 3-week albendazole), 5 (39%; 5-weeks albendazole) and 2 (22%; 3-week albendazole plus single dose ivermectin) participants met the primary outcome of microfilaraemia below 100/ml at day 168. A 80-90% reduction of microfilaraemia was observed in the active treatment groups.

Conclusion: The 5-week regimen of albendazole or a 3-week regimen of albendazole followed by ivermectin were most efficacious to reduce microfilaraemia. All therapeutic regimens were well tolerated and safe.

Trial registration: Trial registered at the Pan-African Clinical Trials Registry: PACTR201807197019027.

Background: The dynamics of the spread of cholera epidemics in the Democratic Republic of the Congo (DRC), from east to west and within western DRC, have been extensively studied. However, the drivers of these spread processes remain unclear. We therefore sought to better understand the factors associated with these spread dynamics and their potential underlying mechanisms.

Methods: In this eco-epidemiological study, we focused on the spread processes of cholera epidemics originating from the shores of Lake Kivu, involving the areas bordering Lake Kivu, the areas surrounding the lake areas, and the areas out of endemic eastern DRC (eastern and western non-endemic provinces). Over the period 2000-2018, we collected data on suspected cholera cases, and a set of several variables including types of conflicts, the number of internally displaced persons (IDPs), population density, transportation network density, and accessibility indicators. Using multivariate ordinal logistic regression models, we identified factors associated with the spread of cholera outside the endemic eastern DRC. We performed multivariate Vector Auto Regressive models to analyze potential underlying mechanisms involving the factors associated with these spread dynamics. Finally, we classified the affected health zones using hierarchical ascendant classification based on principal component analysis (PCA).

Findings: The increase in the number of suspected cholera cases, the exacerbation of conflict events, and the number of IDPs in eastern endemic areas were associated with an increased risk of cholera spreading outside the endemic eastern provinces. We found that the increase in suspected cholera cases was influenced by the increase in battles at lag of 4 weeks, which were influenced by the violence against civilians with a 1-week lag. The violent conflict events influenced the increase in the number of IDPs 4 to 6 weeks later. Other influences and uni- or bidirectional causal links were observed between violent and non-violent conflicts, and between conflicts and IDPs. Hierarchical clustering on PCA identified three categories of affected health zones: densely populated urban areas with few but large and longer epidemics; moderately and accessible areas with more but small epidemics; less populated and less accessible areas with more and larger epidemics.

Conclusion: Our findings argue for monitoring conflict dynamics to predict the risk of geographic expansion of cholera in the DRC. They also suggest areas where interventions should be appropriately focused to build their resilience to the disease.