Community acceptability, participation, and adherence to mass drug administration with primaquine for Plasmodium vivax elimination in Southern Thailand: a mixed methods approach.

BACKGROUND: Mass drug administration (MDA) with primaquine (PQ) is being considered for accelerating Plasmodium vivax elimination in remaining active foci. This study aimed to determine the acceptability of MDA with PQ in malaria endemic villages in a malarious setting in the South of Thailand undergoing MDA with PQ. METHODS: A cross-sectional mixed-methods approach was conducted in seven malaria endemic villages where MDA with PQ was implemented. The data were collected from community villagers and health workers using structured questionnaires, in-depth interviews, and focus group discussions. Descriptive statistics and logistic regression models were used for quantitative data analysis. Thematic analysis was applied for qualitative data. RESULTS: Among a total of 469 participants from the MDA villages, 293 participants were eligible for MDA with PQ and 79.86% (234) completed 14-days of PQ. The logistic regressions indicated that males (adjusted odds ratio: 2.52 [95% confidence interval: 1.33-4.81]) and those who are farmers (2.57 [1.12-5.90]) were most likely to participate in the MDA. Among 293 participants in the post-MDA study, 74.06% had originally agreed to participate in the MDA with PQ while 25.94% had originally reported not wanting to participate in the MDA. Of those who originally reported being willing to participate in the MDA, 71.23% followed through with participation in the first or second round. Conversely, 93.24% of those who originally reported not being willing to participate in the MDA did in fact participate in the MDA. Factors contributing to higher odds of agreeing to participate and following through with participation included being male (1.98 [1.06-3.69]) and correctly responding that malaria is preventable (2.32 [1.01-5.35]) with some differences by village. Five key themes emerged from the qualitative analyses: concern about side effects from taking PQ; disbelief that malaria could be eliminated in this setting; low overall concern about malaria infections; misunderstandings about malaria; and a general need to tailor public health efforts for this unique context. CONCLUSION: While the reported likelihood of participating in MDA was high in this setting, actual follow-through was relatively moderate, partially because of eligibility (roughly 71% of those in the follow-up survey who originally agreed to participate actually followed through with participation). One of the largest concerns among study participants was PQ-related side effects-and these concerns likely heavily influenced participant adherence to the MDA. The results of this study can be used to tailor future MDAs, or other public health interventions, in this and potentially other similar settings.

Impact of dengue-preventive behaviors on Aedes immature production in Bang Kachao, Samut Prakan Province, Thailand: a cross-sectional study.

BACKGROUND: Controlling sites where mosquitos breed is a key strategy in breaking the cycle of infectious transmission of the dengue virus. Preventive behaviors, such as covering water containers with lids and adding temephos (commercially named Abate sand) in water containers are needed to reduce and control mosquito breeding sites. This study aimed to investigate the impact of dengue-preventive behaviors on Aedes immature production. METHODS: This cross-sectional study used in-person interviews to record occurrence of dengue-preventive behaviors in Bang Kachao, Samut Prakan Province, Thailand. Larval mosquitos in and around houses were observed and recorded, and covered 208 households. RESULTS: It was found that 50% of these households had containers for drinking water and 94% used water containers. Covering water containers with effective lids showed the best success among dengue-preventive behaviors for reducing Aedes immature production. Adding temephos in water containers also was effective. CONCLUSIONS: Such behaviors substantively affected development of Aedes immatures in and around households.

Factors associated with dengue prevention behaviour in Lowokwaru, Malang, Indonesia: a cross-sectional study.

BACKGROUND: Dengue prevention is important for controlling the spread of dengue infection. Transmission of dengue can be prevented by controlling mosquito breeding sites. Indonesia has dengue a prevention program to minimize mosquito breeding sites known as 3 M Plus. This study aimed to investigate factors associated with dengue prevention behaviour among respondents in the Lowokwaru subdistrict, an urban area in Malang, Indonesia. METHODS: This cross-sectional study used a semi-structured questionnaire that was conducted by face-to-face interview. RESULTS: Older respondents (> 60 years and 41-60 years) showed better dengue prevention behaviour than younger respondents (21-40 years and < 21 years) (p value = 0.01). Proportionally more male respondents showed poor dengue prevention behaviour compared with female respondents (p value = 0.007). Respondents who lived in Malang for long durations showed better dengue prevention behaviour compared with those who lived there for a shorter period (p value = 0.016). Those with more family members in their households practiced better dengue prevention behaviour compared with those with fewer family members (p value = 0.004). Perception was associated with dengue prevention behaviour. Respondents who had higher perceived susceptibility showed better dengue prevention behaviour compared with those who had moderate perceptions (p value = 0.000). CONCLUSIONS: Age, gender, duration of stay in Malang, number of family members, and perception of dengue susceptibility were associated with dengue prevention behaviour.

Liver fluke infection and cholangiocarcinoma: a review.

Parasites are significant groups for carcinogenesis among which liver flukes, including Opisthorchis viverrini and Clonorchis sinensis, are typical representatives causing cholangiocarcinoma (CCA), the second most common primary hepatic malignancy with dismal prognosis. O. viverrini is prevalent in Southeast Asia, infecting 10 million people while C. sinensis has a wider distribution in East Asia and several Southeast Asian countries, affecting more than 35 million people's health. These two worms have some common characteristics and/or discrepancies in life cycle, genome, and transcriptome. As hot spots in recent years, genome and transcriptome research has extracted numerous novel fluke worm-derived proteins, which are excellent for carcinogenic exploration. However, just a handful of these studies have focused on the metabolic pathway. In this study, the main mechanisms of carcinogenesis of both worms, in terms of mechanical damage, metabolic products and immunopathology, and other possible pathways, will be discussed in detail. This review retrospectively describes the main traits of C. sinensis and O. viverrini, their molecular biology and core carcinogenic mechanisms in a contrast pattern.

Promoting community malaria control in rural Myanmar through an active community participation program using the participatory learning approach.

INTRODUCTION: Malaria is prevalent in more than 80% of townships in Myanmar. The National Malaria Control Programme (NMCP) has been implementing community-based malaria control programs nationwide. However, these programs are mostly developed and directed by health authorities, while communities are passively involved. This study aimed to increase community participation in malaria control and promote community malaria control knowledge and practice in rural Myanmar. METHODS: A community-based study, which employed a mixed method approach, collecting data quantitatively and qualitatively, was conducted in two rural villages. The study implemented an active community participation program (ACPP) using the participatory learning approach in a village (ACPP village) but only routine malaria control was given in another village (non-ACPP village). All households with 142 and 96 household representatives from ACPP and non-ACPP villages participated in baseline and endline surveys. The ACPP was evaluated by process and outcome indicators. A spider gram analysis using five process indicators was applied to evaluate the process of the ACPP. Community participation status in malaria control activities and level of community malaria knowledge and practice were determined as outcomes of the ACPP. RESULTS: The spider gram analysis showed that three indicators (needs assessment and planning, leadership and resource mobilization) gained a score of 4, the organization indicator a score of 5 and the management and evaluation indicator a score of 3. The outcome indicators of the program at 6 months showed that the community participation in malaria control activities in the ACPP village had significantly increased (6.9% to 49.3%) (p<0.001). The program promoted community malaria control knowledge and practice in the ACPP village. The mean scores of knowledge, perception, preventive behavior and treatment-seeking behavior were increased significantly, from 3.0 to 5.9 (p<0.001), 20.1 to 21.0 (p<0.001), 3.4 to 4.2 (p<0.001) and 3.1 to 5.6 (p<0.001), respectively. However, no significant change of outcome indicators was found in the non-ACPP village. CONCLUSIONS: The ACPP implemented by community volunteers using the participatory learning approach was feasible in community-based malaria control. This study suggests several features in the ACPP model that may be useful strategies for the implementation of the current NMCP programs in similar rural settings; however, the effect of the ACPP over a longer period to ascertain the impact of such community participation has yet to be further studied.

Health education and factors influencing acceptance of and willingness to pay for influenza vaccination among older adults.

BACKGROUND: The influenza vaccine is recommended in older population. However the immunization coverage varies globally. It has been reported as low as 10-20 % in some countries. This study explored the acceptance of and willingness to pay for influenza vaccination, comparing acceptance and willingness to pay before and after health education. METHODS: The study was conducted with 2693 older people in Bangkok, Thailand. Participants were divided into an education group (n = 1402) and a control group (n = 1291). A validated questionnaire measuring acceptance of and willingness to pay for vaccination was administered during semi-structured interviews before and after education. Data on factors influencing acceptance were analyzed. RESULTS: Participants' mean age was 69.5 years, 80 % were women and 82.1 % had at least one co-morbidity. Of the participants, 43.5 % had previously received vaccination more than once, although 92.8 % expressed acceptance of vaccination. Acceptance was associated with a positive attitude toward vaccination (OR 2.1, 95 % CI 1.5-2.9) and a history of receiving vaccination (OR 4.1, 95 % CI 2.8-6.1). At baseline, there were no differences between the education and control groups in terms of work status (p = 0.457), co-morbidities (p = 0.07), medical status (p = 0.243), and previous vaccination (p = 0.62), except for educational background (p = 0.004). Acceptance of vaccination increased to 95.8 % (p < 0.001) after education and willingness to pay increased to 82.1 % (p < 0.001). Education significantly affected those with primary school-level education and no previous vaccination history, with acceptance increasing from 83.3 to 92.6 % (p < 0.001); more than twice as high as the control group (OR 2.4, 95 % CI 1.2-4.7). Viewing an educational video increased the proportion of participants with a high level of knowledge from 29.2 to 49.2 % (p < 0.001), and increased the proportion of participants with a positive attitude from 52.4 to 70.7 % (p <0.001). No significant difference was found in any parameter between the first and second assessment in the control group. CONCLUSIONS: The strategies to increase positive attitudes may enhance the acceptance of vaccination. Health education using an educational video demonstrated a significant impact on acceptance, willingness to pay, knowledge and attitude in older people. This may lead to increased sustainability of the immunization program in older people.

AcCystatin, an immunoregulatory molecule from Angiostrongylus cantonensis, ameliorates the asthmatic response in an aluminium hydroxide/ovalbumin-induced rat model of asthma.

Epidemiological surveys have demonstrated that helminth infections are negatively related to atopic diseases, including asthma. Defining and characterising specific helminth molecules that have excellent immunomodulatory capacities as potential therapeutics for the treatment or prophylaxis of allergic manifestations are of great interest. AcCystatin, a cystatin protease inhibitor of Angiostrongylus cantonensis, is a homologue of other nematode cystatins with immunoregulatory properties. Here, we aim to determine the effects of AcCystatin on an ovalbumin/aluminium hydroxide (OVA/Al[OH]3)-induced rat model of asthma. Wistar rats were randomly divided into four groups, including a control group, an OVA/Al[OH]3-induced asthma group, a group receiving AcCystatin immunisation prior to OVA/Al[OH]3-induced asthma and a group receiving AcCystatin treatment after OVA/Al[OH]3-induced asthma. The numbers of eosinophils, basophils, neutrophils, lymphocytes and monocytes in the peripheral blood and of eosinophils in the bronchoalveolar lavage fluid (BALF) were counted for each animal. The expression levels of the cytokines interferon-γ, interleukin (IL) 4, IL-5, IL-6, IL-10, IL17A and tumour necrosis factor receptor-α in BALF, of OVA-specific immunoglobulin E in BALF and serum and of the chemokines eotaxin-1, eotaxin-2, eotaxin-3, MCP-1 and MCP-3 in lung tissue were measured. In addition, the degree of peribronchial and perivascular inflammation and the intensity of goblet cell metaplasia were qualitatively evaluated. The sensitised/challenged rats developed an extensive cell inflammatory response of the airways. AcCystatin administration significantly reduced the cellular infiltrate in the perivascular and peribronchial lung tissues and reduced both goblet mucous production and eosinophil infiltration. The rats that were treated with AcCystatin before or after sensitisation with OVA showed significant decreases in eotaxin-1, eotaxin-3 and MCP-1 expression in the lung tissue. The production of IL-4, IL-5, IL-6 and IL-17A and of OVA-specific IgE antibodies was also significantly reduced in AcCystatin-treated rats compared with untreated asthmatic rats. The AcCystatin treatment was associated with a significant increase in IL-10 levels. Our present findings provide the first demonstration that AcCystatin is an effective agent in the prevention and treatment of the airway inflammation associated with asthma.

Factors hindering coverage of targeted mass treatment with primaquine in a malarious township of northern Myanmar in 2019-2020.

Targeted mass primaquine treatment (TPT) might be an effective intervention to facilitate elimination of vivax malaria in Myanmar by 2030. In this study, we explored the factors hindering coverage of a TPT campaign conducted in a malarious township of northern Myanmar. From August 2019 to July 2020, a cross-sectional exploratory design including quantitative and qualitative data was conducted in five villages with high P. vivax prevalence following a TPT campaign. Among a targeted population of 2322; 1973 (85.0%) participated in the baseline mass blood survey (MBS) and only 52.0% of the total targeted population (1208, 91.9% of total eligible population) completed the TPT. G6PD deficiency was found among 13.5% of total MBS participants and those were excluded from TPT. Of 1315 eligible samples, farmers and gold miners, males, and those aged 15 to 45 years had higher percentages of non-participation in TPT. Qualitative findings showed that most of the non-participation groups were outside the villages during TPT because of time-sensitive agricultural and other occupational or education-related purposes. In addition to mitigating of some inclusion criteria (i.e. including young children or offering weekly PQ treatment to G6PD deficient individuals), strengthening community awareness and increasing engagement should be pursued to increase community participation.

Medical students' confidence and competence with prescribing in ST-elevation myocardial infarction: a mixed-methods study.

Objectives: To explore factors associated with prescribing confidence and competence of final-year medical students for prescribing antiplatelet and fibrinolytic agents in ST-segment elevation myocardial infarction (STEMI). Methods: The study was conducted among final-year medical students with a triangular convergent mixed-methods approach. First, an online survey was conducted using a voluntary sampling method with concurrent in-depth interviews performed. The survey data was analysed using descriptive statistics and paired t-tests, while survey factors were compared using the chi-squared or Fisher's exact test. The interview data were coded and analysed thematically. The relations between the qualitative and quantitative findings were finally described. Results: Totally 92 validly replied to the questionnaire, and 20 participated in the interviews. The quantitative analysis indicated that they had high competence in the diagnosis of STEMI and prescribing antiplatelet and fibrinolytic agents. The mean confidence score of prescribing for both was medium and was significantly lower in fibrinolytic agents. (M=3.3, SD=1.1 vs. M=2.8, SD=1.0, t(91)=5.39, p<0.01). Their experience, knowledge, and mentoring were accounted for, considering the prescribing confidence factors in both approaches. Besides, providing guidelines and standing orders were derived from the interview data. Conclusions: This study has demonstrated that final-year medical students have a high ability to diagnose and prescribe essential medications in STEMI but tend to have low confidence in prescribing fibrinolytic agents. Experiential learning, mentorship and providing guidelines can help them, especially in emergency settings to prescribe confidently and safely. Further multicenter studies on undergraduate and graduate medical students' confidence and perspective of prescribing are required, especially for high-alert medications.

Effects of an incinerator project on a healthcare-waste management system.

This evaluative research study aimed to assess the effects of the central healthcare incinerator project on waste management in Yala Province. The study data were collected twice: at baseline and during the operational phase. A combination of structured interview and observation were used during data collection. The study covered 127 healthcare facilities: government hospitals, healthcare centres, and private clinics. The results showed 63% of healthcare risk waste (HCRW) handlers attended the HCRW management training. Improvements in each stage of the HCRW management system were observed in all groups of facilities. The total cost of the HCRW management system did not change, however; the costs for hospitals decreased, whereas those for clinics increased significantly. It was concluded that the central healthcare waste incinerator project positively affected HCRW management in the area, although the costs of management might increase for a particular group. However, the benefits of changing to a more appropriately managed HCRW system will outweigh the increased costs.

The acceptability of targeted mass treatment with primaquine for local elimination of vivax malaria in a northern Myanmar township: a mixed-methods study.

BACKGROUND: Radical cure of the Plasmodium vivax latent liver stage is required to effectively manage vivax malaria. Targeted mass treatment with primaquine may be an effective mechanism for reducing reservoirs of the disease. Since community engagement and high coverage are essential for mass treatment programs, this study aimed to determine the acceptability of mass primaquine treatment in a targeted community in a northern Myanmar township. METHODS: A cross-sectional mixed-methods study was deployed among household leaders in July 2019. Face-to-face interviews using structured questionnaires and standardized qualitative guidelines were conducted to gather information. Descriptive and inferential statistics, including logistic regression models, were applied. RESULTS: Among 609 study respondents, > 90% agreed to participate in an upcoming targeted mass primaquine treatment (TPT) program. Factors contributing to higher odds of acceptability of the program were older age [adjusted odds ratios (aOR): 2.38, 95% confidence intervals (CI) 1.08-8.96], secondary education level (aOR: 3.99, 95% CI 1.12-20.01), having good knowledge of malaria (aOR: 2.12, 95% CI 1.04-4.76), experiencing malaria within the family (aOR: 1.92, 95% CI 1.14-5.13), and believing eliminating malaria from the village is possible (aOR: 2.83, 95% CI 1.07-4.07). Furthermore, 50 community respondents, 6 midwives, and 4 public health staff (grade II) participated in the qualitative component of the study. Many thought that TPT seemed feasible and stressed that high coverage of underserved groups and health education are needed before commencing the activity. CONCLUSIONS: Most respondents agreed to participate in the proposed mass treatment campaign. Older people with secondary education level and those who had experienced malaria within their families were most likely to report willingness to participate. These same individuals may be important in the community engagement process to increase community acceptance of the program.

Urinary levels of phthalates and DINCH metabolites in Korean and Thai pregnant women across three trimesters.

Phthalates are anti-androgenic chemicals and may cause long-lasting adverse effects on growing fetuses. Understanding their exposure profile during pregnancy, therefore, is of public health importance. Because both behavioral and physiological changes of pregnant women are expected to be substantial, the amount of phthalate exposure is expected to vary significantly over the course of pregnancy. Temporal trend of phthalate exposure during pregnancy, however, is largely unknown, especially in Asian women. The purpose of this study is to investigate the urinary concentrations of metabolites for major phthalates and alternative plasticizers over the course of pregnancy among Korean (n = 81) and Thai women (n = 102). Twenty-four metabolites from 15 plasticizers, such as dimethyl phthalate (DMP), diethyl phthalate (DEP), di-isobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP), benzyl butyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), dioctyl phthalate (DnOP), diisononyl phthalate (DiNP), diisodecyl phthalate (DiDP), di(2-ethylhexyl) terephthalate (DEHTP), and di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH), were measured in urine samples collected in each trimester from pregnant women. While the levels of several phthalate metabolites were significantly different by trimester among Korean women, those of Thai women were relatively consistent. Urinary metabolites of DEP and DnOP were higher in Thai pregnant women compared to Korean pregnant women. The detection frequencies of the DINCH metabolite were 67.4% and 44.9% among Korean and Thai pregnant women, respectively. However, the ratio of DINCH to DEHP metabolites was significantly higher in Thai women. According to risk assessment, 11.9% of Korean and 5.3% of Thai women were considered at risk due to phthalate exposure, and DEHP, DnBP and DiBP were identified as major risk drivers. Considering the vulnerability of growing fetuses, further studies are warranted to identify major sources of exposure to these plasticizers during pregnancy.

Testing the Effectiveness and Cost-Effectiveness of a Combination HIV Prevention Intervention Among Young Cisgender Men Who Have Sex With Men and Transgender Women Who Sell or Exchange Sex in Thailand: Protocol for the Combination Prevention Effectiveness Study.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is highly effective in the prevention of HIV acquisition, particularly for men who have sex with men (MSM). Questions remain on the benefits of PrEP and implementation strategies for those at occupational risk of HIV acquisition in sex work, as well as on methods to support adherence among young people who initiate PrEP. OBJECTIVE: The Combination Prevention Effectiveness study for young cisgender MSM and transgender women (TGW) aims to assess the effectiveness and cost-effectiveness of a combination intervention among HIV-uninfected young MSM and TGW engaged in sex work in Thailand. METHODS: This open-label, nonrandomized assessment compares the relative effectiveness of a combination prevention intervention with and without daily oral emtricitabine and tenofovir disoproxil fumarate (Truvada) PrEP with SMS-based adherence support. HIV-uninfected young MSM and TGW aged 18 to 26 years in Bangkok and Pattaya who self-report selling/exchanging sex at least once in the previous 12 months are recruited by convenience sampling and peer referral and are eligible regardless of their intent to initiate PrEP. At baseline, participants complete a standard assessment for PrEP eligibility and may initiate PrEP then or at any time during study participation. All participants complete a survey and HIV testing at baseline and every 3 months. Participants who initiate PrEP complete monthly pill pickups and may opt-in to SMS reminders. All participants are sent brief weekly SMS surveys to assess behavior with additional adherence questions for those who initiated PrEP. Adherence is defined as use of 4 or more pills within the last 7 days. The analytic plan uses a person-time approach to assess HIV incidence, comparing participant time on oral PrEP to participant time off oral PrEP for 12 to 24 months of follow-up, using a propensity score to control for confounders. Enrollment is based on the goal of observing 620 person-years (PY) on PrEP and 620 PY off PrEP. RESULTS: As of February 2019, 445 participants (417 MSM and 28 TGW) have contributed approximately 168 PY with 95% (73/77) retention at 12 months. 74.2% (330/445) of enrolled participants initiated PrEP at baseline, contributing to 134 PY of PrEP adherence, 1 PY nonadherence, and 33 PY PrEP nonuse/noninitiation. Some social harms, predominantly related to unintentional participant disclosure of PrEP use and peer stigmatization of PrEP and HIV, have been identified. CONCLUSIONS: The majority of cisgender MSM and TGW who exchange sex and participate in this study are interested in PrEP, report taking sufficient PrEP, and stay on PrEP, though additional efforts are needed to address community misinformation and stigma. This novel multilevel, open-label study design and person-time approach will allow evaluation of the effectiveness and cost-effectiveness of combination prevention intervention in the contexts of both organized sex work and exchanged sex. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/15354.

Snail-borne parasitic diseases: an update on global epidemiological distribution, transmission interruption and control methods.

BACKGROUND: Snail-borne parasitic diseases, such as angiostrongyliasis, clonorchiasis, fascioliasis, fasciolopsiasis, opisthorchiasis, paragonimiasis and schistosomiasis, pose risks to human health and cause major socioeconomic problems in many tropical and sub-tropical countries. In this review we summarize the core roles of snails in the life cycles of the parasites they host, their clinical manifestations and disease distributions, as well as snail control methods. MAIN BODY: Snails have four roles in the life cycles of the parasites they host: as an intermediate host infected by the first-stage larvae, as the only intermediate host infected by miracidia, as the first intermediate host that ingests the parasite eggs are ingested, and as the first intermediate host penetrated by miracidia with or without the second intermediate host being an aquatic animal. Snail-borne parasitic diseases target many organs, such as the lungs, liver, biliary tract, intestines, brain and kidneys, leading to overactive immune responses, cancers, organ failure, infertility and even death. Developing countries in Africa, Asia and Latin America have the highest incidences of these diseases, while some endemic parasites have developed into worldwide epidemics through the global spread of snails. Physical, chemical and biological methods have been introduced to control the host snail populations to prevent disease. CONCLUSIONS: In this review, we summarize the roles of snails in the life cycles of the parasites they host, the worldwide distribution of parasite-transmitting snails, the epidemiology and pathogenesis of snail-transmitted parasitic diseases, and the existing snail control measures, which will contribute to further understanding the snail-parasite relationship and new strategies for controlling snail-borne parasitic diseases.

Apoptosis and necroptosis of mouse hippocampal and parenchymal astrocytes, microglia and neurons caused by Angiostrongylus cantonensis infection.

BACKGROUND: Angiostrongylus cantonensis has been the only parasite among Angiostrongylidae to cause human central nervous system infection characterized by eosinophilic meningitis or meningoencephalitis. The mechanism of the extensive neurological impairments of hosts caused by A. cantonensis larvae remains unclear. The aim of the present study was to investigate apoptosis, necroptosis and autophagy in the brains of mice infected with A. cantonensis, which will be valuable for better understanding the pathogenesis of angiostrongyliasis cantonensis. METHODS: Functional and histological neurological impairments of brain tissues from mice infected with A. cantonensis were measured by the Morris water maze test and haematoxylin and eosin (H&E) staining, respectively. The transcriptional and translational levels of apoptosis-, necroptosis- and autophagy-related genes were quantified by quantitative real-time polymerase chain reaction (RT-PCR), and assessed by western blot and immunohistochemistry (IHC) analysis. Apoptotic and necroptotic cells and their distributions in infected brain tissues were analysed by flow cytometry and transmission electron microscopy (TEM). RESULTS: Inflammatory response in the central nervous system deteriorated as A. cantonensis infection evolved, as characterized by abundant inflammatory cell infiltration underneath the meninges, which peaked at 21 days post-infection (dpi). The learning and memory capacities of the mice were significantly decreased at 14 dpi, indicating prominent impairment of their cognitive functions. Compared with those of the control group, the mRNA levels of caspase-3, -4, -6, and RIP3 and the protein levels of caspase-4, cleaved caspase-3, cleaved caspase-6, RIP3, and pRIP3 were obviously elevated. However, no changes in the mRNA or protein levels of FADD, Beclin-1 or LC3B were evident, indicating that apoptosis and necroptosis, but not autophagy, occurred in the brain tissues of mice infected with A. cantonensis. The quantitative RT-PCR, western blot, IHC, flow cytometry and TEM results further revealed the apoptotic and necroptotic microglia, astrocytes and neurons in the parenchymal and hippocampal regions of infected mice. CONCLUSIONS: To our knowledge, we showed for the first time that A. cantonensis infection causes the apoptosis and necroptosis of microglia and astrocytes in the parenchymal and hippocampal regions of host brain tissues, further demonstrating the pathogenesis of A. cantonensis infection and providing potential therapeutic targets for the management of angiostrongyliasis.

Factors related to volunteer comprehension of informed consent for a clinical trial.

The informed consent process has become a universal requirement for research involving human subjects. Its goal is to inform volunteers regarding research in order to make decision to participate or not. This study aimed to measure volunteers' comprehension levels concerning the clinical trial and to find out factors associated with that comprehension levels. Eighty-one volunteers who enrolled in a malaria clinical trial were recruited into the study. A semi-structured questionnaire was used to collect the information. Non-participant observation was used to observe the process of informed consent. Volunteers were interviewed three days after being recruited into the trial. The results show the volunteers' comprehension was low. Only 44% of volunteers had an acceptable level of comprehension. It also revealed that 20 volunteers were not aware of being volunteers. Most volunteers knew about the benefits of participating in the trial and realized that they had the right to withdraw from the study, but not many knew about the risks of the trial. The results indicated the method of informing about the trial affected the volunteers' comprehension level. No relationship was found between comprehension level and volunteers' socio-demographic characteristics and their attitude toward the consent process. The findings from this study demonstrate volunteers who participated in the clinical trial were not truly informed. Further studies regarding enhancing volunteers' understanding of the trial are needed.

Modified Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) as a screening test for dementia for Thai elderly.

A potential test for early detection of dementia in the elderly is the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), which is based on information from the informant for the elderly about the changes of the elderly in everyday cognitive functioning associated with dementia. The present study aimed to modify and assess the reliability and validity of the modified IQCODE consisting of 32 items. The study consisted of two methods of assessing dementia: DSMIV diagnosis carried out by clinicians, and informants responding to the IQCODE. The subjects were 200 pairs of elderly subjects and their informants who visited the Geriatric Clinic, Ramathibodi Hospital. The optimal cutoff score on the modified IQCODE was 3.42, with 90% sensitivity and 95% specificity. The positive predictive values, negative predictive values, and accuracy were 0.94, 0.90, and 0.92, respectively. The IQCODE items had high internal consistency. The IQCODE associated with the elderly person's age, but not with their gender and educational level; nor were they associated with the demographic characteristics of the informant. Therefore, the IQCODE could be used as an alternative screening test for dementia in Thailand with acceptable sensitivity and specificity. This tool may be useful for dementia screening in the community and the geriatric clinic for early detection of disease.

SjCa8, a calcium-binding protein from Schistosoma japonicum, inhibits cell migration and suppresses nitric oxide release of RAW264.7 macrophages.

BACKGROUND: Schistosomiasis is considered second only to malaria as the most devastating parasitic disease in tropical countries. Schistosome cercariae invade the host by penetrating the skin and migrate though the lungs and portal circulation to their final destination in the hepatic portal system and eventually the mesenteric veins. Previous studies have shown that the cytotoxic pathways that target schistosomulum in the lung-stage involve nitric oxide (NO) produced by macrophages. By contrast, skin-stage schistosomulas can evade clearance, indicating that they might be freed from macrophage NO-mediated cytotoxicity to achieve immune evasion; however, the critical molecules and mechanisms involved remain unknown. METHODS: Recombinant SjCa8 (rSjCa8), an 8-kDa calcium-binding protein that is stage-specifically expressed in cercaria and early skin-stage schistosomulas of Schistosoma japonicum, was incubated with mouse RAW264.7 macrophages. Effects on macrophage proliferation were determined using Cell Counting Kit-8. Next, transwell assay was carried out to further investigate the role of rSjCa8 in macrophage migration. The effects of rSjCa8 on macrophage apoptosis were evaluated using confocal microscopy and flow cytometry. Additional impacts of rSjCa8 on NO release by lipopolysaccharide (LPS)-stimulated macrophages as well as the underlying mechanisms were explored using fluorescent probe, nitric oxide signaling pathway microarray, quantitative real-time PCR, mutagenesis, and neutralizing antibody approaches. RESULTS: rSjCa8 exhibited a striking inhibitory effect on macrophage migration, but did not markedly increase cell proliferation or apoptosis. Additionally, rSjCa8 potently inhibited NO release by LPS-stimulated macrophages in a dose- and time-dependent manner, and the inhibitory mechanism was closely associated with intracellular Ca(2+) levels, the up-regulation of catalase expression, and the down-regulation of the expression of 47 genes, including Myc, Gadd45a, Txnip, Fas, Sod2, Nos2, and Hmgb1. Vaccination with rSjCa8 increased NO concentration in the challenging skin area of infected mice and reduced the number of migrated schistosomula after skin penetration by cercariae. CONCLUSIONS: Our findings indicate that SjCa8 might be a novel molecule that plays a critical role in immune evasion by S. japonicum cercaria during the process of skin penetration. The inhibitory impacts of rSjCa8 on macrophage migration and [Ca(2+)]i-dependent NO release suggest it might represent a novel vaccine candidate and chemotherapeutic target for the prevention and treatment of schistosomiasis.

Gender difference in treatment seeking behaviors of tuberculosis cases in rural communities of Bangladesh.

This descriptive cross-sectional study was conducted to investigate gender differences in the epidemiological factors associated with the treatment seeking behaviors of TB cases in the rural communities of Bangladesh. The study reveals that there is significant gender difference in treatment seeking behaviors of rural TB cases and the majority of them (52%) have taken prior treatment from various traditional healers, 70% of them are females who attended health centers (UZHCs) as the other choice (adjusted OR: 4.2, 95% CI: 2.0-8.4). It was found that the mean patient delay was 63 days (range 14-210 days) where half of the females delayed more than 60 days while they were spreading their disease. The study findings reveal gender differences in treatment seeking behaviors associated with socio-cultural barriers, particularly among females in their access to TB care. Fifty-five percent of cases wanted the diagnosis of TB remain confidential to avoid being labeled as TB patients, where 82.7% were female, 85.6% of female TB patients had problems in their relationships with their spouse (61%) and family members (58%) after being diagnosed with TB. The results of the TB service factors found that 39% of females were not satisfied with their provider's behaviors, which was significantly associated with treatment seeking behavior (adjusted OR: 2.6, 95% CI: 1.0-6.6). The study findings strongly suggest that there was a significant gender difference in treatment seeking behavior in rural Bangladesh. Based on the study findings, we recommend developing an appropriate gender strategy for developing a TB control program, comprised of operational, socio-cultural and community awareness interventions aimed at treating undiscovered reservoirs of female TB cases in rural Bangladesh.

Linalool, derived from Cinnamomum camphora (L.) Presl leaf extracts, possesses molluscicidal activity against Oncomelania hupensis and inhibits infection of Schistosoma japonicum.

BACKGROUND: Schistosomiasis japonicum remains a considerable economic and public health concern in China, the Philippines and Indonesia. Currently available measures to control the unique intermediate host Oncomelania hupensis are frequently associated with severe side effects. Previous studies have demonstrated that linalool-rich extracts from various plants exhibited promising biological activities including cytotoxic, anti-microbial and anti-parasitic properties. METHODS: We identified the components of leaf extracts from Cinnamomum camphora by gas chromatography coupled to mass spectrometry (GC-MS) and investigated molluscicidal and larvicidal effects of linalool against O. hupensis and Schistosoma japonicium. The ultrastructural alterations in gills, salivary gland, stomach and hepatopancreas of snails were observed under the light microscope and transmission electron microscope, and lesions to tegument of cercaria were examined under a light microscope and fluorescence microscope. We then evaluated the effects of linalool on skin penetration and migration of schistosomula and adult survival by measurement of worm burden and egg counts in Balb/C mice infected with linalool-treated cercariae. RESULTS: In the present work, 44 components were identified from the leaf extracts of C. camphora, of which linalool was the most abundant constituent. Linalool exhibited the striking molluscicidal and larvicidal effects with LC50 = 0.25 mg/L for O. hupensis and LC50 = 0.07 mg/L for cercaria of S. japonicium. After exposure to linalool, damage to the gills and hepatopancreas of the snails, and to the tegument and body-tail joint of cercariae was apparent. In addition, linalool markedly reduced the recovered schistosomulum from mouse skin after challenge infection, and therefore decreased the worm burden in infected animals, but not fecundity of female adults of the parasite. CONCLUSIONS: Our findings indicated that linalool might be a novel chemotherapeutic agent against S. japonicium and the snail intermediate host.