The knowledge, attitude and practice of community people on dengue fever in Central Nepal: a cross-sectional study.

BACKGROUND: Since 2006, Nepal has experienced frequent Dengue fever (DF) outbreaks. Up to now, there have been no knowledge, attitude and practice (KAP) studies carried out on DF in Nepal that have included qualitative in-depth and quantitative data. Thus, we aimed to explore and compare the KAP of people residing in the lowland (< 1500 m) and highland (> 1500 m) areas of Nepal. METHODS: A cross-sectional mixed-method study was conducted in six districts of central Nepal in September-October 2018 including both quantitative (660 household surveys) and qualitative data (12 focus group discussions and 27 in-depth interviews). The KAP assessment was executed using a scoring system and defined as high or low based on 80% cut-off point. Logistic regression was used to investigate the associated factors, in quantitative analysis. The deductive followed by inductive approach was adopted to identify the themes in the qualitative data. RESULTS: The study revealed that both the awareness about DF and prevention measures were low. Among the surveyed participants, 40.6% had previously heard about DF with a significantly higher number in the lowland areas. Similarly, IDI and FGD participants from the lowland areas were aware about DF, and it's associated symptoms, hence they were adopting better preventive practices against DF. The findings of both the qualitative and quantitative data indicate that people residing in the lowland areas had better knowledge on DF compared to people in highland areas. All IDI participants perceived a higher chance of increasing future dengue outbreaks due to increasing temperature and the mobility of infected people from endemic to non-endemic areas. The most quoted sources of information were the television (71.8%) and radio (51.5%). Overall, only 2.3% of the HHS participants obtained high knowledge scores, 74.1% obtained high attitude scores and 21.2% obtained high preventive practice scores on DF. Among the socio-demographic variables, the area of residence, educational level, age, monthly income, SES and occupation were independent predictors of knowledge level, while the education level of the participants was an independent predictor of the attitude level. CONCLUSIONS: Our study found a very low level of knowledge and insufficient preventive practices. This highlights an urgent need for extensive dengue prevention programs in both highland and lowland communities of Nepal.

Novel long-chain neurotoxins from Bungarus candidus distinguish the two binding sites in muscle-type nicotinic acetylcholine receptors.

αδ-Bungarotoxins, a novel group of long-chain α-neurotoxins, manifest different affinity to two agonist/competitive antagonist binding sites of muscle-type nicotinic acetylcholine receptors (nAChRs), being more active at the interface of α-δ subunits. Three isoforms (αδ-BgTx-1-3) were identified in Malayan Krait (Bungarus candidus) from Thailand by genomic DNA analysis; two of them (αδ-BgTx-1 and 2) were isolated from its venom. The toxins comprise 73 amino acid residues and 5 disulfide bridges, being homologous to α-bungarotoxin (α-BgTx), a classical blocker of muscle-type and neuronal α7, α8, and α9α10 nAChRs. The toxicity of αδ-BgTx-1 (LD50 = 0.17-0.28 µg/g mouse, i.p. injection) is essentially as high as that of α-BgTx. In the chick biventer cervicis nerve-muscle preparation, αδ-BgTx-1 completely abolished acetylcholine response, but in contrast with the block by α-BgTx, acetylcholine response was fully reversible by washing. αδ-BgTxs, similar to α-BgTx, bind with high affinity to α7 and muscle-type nAChRs. However, the major difference of αδ-BgTxs from α-BgTx and other naturally occurring α-neurotoxins is that αδ-BgTxs discriminate the two binding sites in the Torpedo californica and mouse muscle nAChRs showing up to two orders of magnitude higher affinity for the α-δ site as compared with α-ε or α-γ binding site interfaces. Molecular modeling and analysis of the literature provided possible explanations for these differences in binding mode; one of the probable reasons being the lower content of positively charged residues in αδ-BgTxs. Thus, αδ-BgTxs are new tools for studies on nAChRs.

Social determinants of malaria in an endemic area of Indonesia.

BACKGROUND: Malaria is an increasing concern in Indonesia. Socio-demographic factors were found to strongly influence malaria prevalence. This research aimed to explore the associations between socio-demographic factors and malaria prevalence in Indonesia. METHODS: The study used a cross-sectional design and analysed relationships among the explanatory variables of malaria prevalence in five endemic provinces using multivariable logistic regression. RESULTS: The analysis of baseline socio-demographic data revealed the following independent risk variables related to malaria prevalence: gender, age, occupation, knowledge of the availability of healthcare services, measures taken to protect from mosquito bites, and housing condition of study participants. Multivariable analysis showed that participants who were unaware of the availability of health facilities were 4.2 times more likely to have malaria than those who were aware of the health facilities (adjusted odds ratio = 4.18; 95% CI 1.52-11.45; P = 0.005). CONCLUSIONS: Factors that can be managed and would favour malaria elimination include a range of prevention behaviours at the individual level and using the networks at the community level of primary healthcare centres. This study suggests that improving the availability of a variety of health facilities in endemic areas, information about their services, and access to these is essential.

Knowledge and attitude towards pregnancy-related issues of Zika virus infection among general practitioners in Indonesia.

BACKGROUND: The aim of this study was to assess the knowledge and attitudes towards pregnancy-related issues of Zika virus (ZIKV) infection among general practitioners (GPs), a frontline healthcare worker group, in Indonesia. METHODS: A cross-sectional, online survey assessing knowledge and attitudes towards ZIKV infection on multiple-item scales was sent to GPs in the Sumatra and Java islands of Indonesia. The associations between independent factors and either knowledge or attitude were assessed with logistic regressions. The correlation and association between knowledge and attitude were estimated. RESULTS: We included 457 (53.7%) out of 850 responses in the analysis. Among these, 304 (66.5%) and 111 (24.2%) respondents had a good knowledge and attitude, respectively. No demographic, workplace, professional development, or experiential characteristics related to ZIKV infection were associated with knowledge. In the multivariate analysis, only contact experience was associated with attitude. There was a significant, positive correlation between knowledge and attitude scores. CONCLUSIONS: Although knowledge of pregnancy-related complications of ZIKV infection is relatively high among GPs in Indonesia, more than 75% of them had a poor attitude towards pregnancy-related issues of Zika. Strategies for enhancing the capacity of GPs to develop positive attitudes and respond to ZIKV infection are needed.

Knowledge and awareness of hepatitis B among households in Malaysia: a community-based cross-sectional survey.

BACKGROUND: Hepatitis B (HepB) is a major public health concern in Malaysia yet little is known about knowledge and awareness of this infection in the country. Such information is essential for designing effective intervention strategies for HepB prevention and control. The aim of this study was to characterize knowledge and awareness regarding HepB in Malaysia and to identify their associated sociodemographic determinants. METHODS: A community-based cross-sectional survey was conducted between January and May 2016 in Selangor state of Malaysia. A two-stage cluster random sampling design was used and one adult member of selected households was interviewed face-to-face. Logistic regression was used to estimate the differences in knowledge and awareness between groups. RESULTS: A total of 764 households completed the interviews and were included in the final analysis. Only 36.9 and 38.8% of the participants had good knowledge and awareness, respectively. The factors associated with good knowledge were being in the 35-44 year age group, Malay ethnicity, high educational attainment and high family income. Being Chinese, being older and having high educational attainment were determinants of having good awareness towards HepB. Participants who had good knowledge were 2.5 times more likely to also have good awareness (OR: 2.41, 95% CI: 1.78-3.26, p < 0.001). CONCLUSIONS: This study reveals a low level of knowledge and awareness of HepB among households in Malaysia. This finding highlights the need to improve public knowledge and awareness through well-designed programs targeting vulnerable groups in order to reduce hepatitis B virus transmission and achieve the governmental target of eliminating viral hepatitis as a public health concern by 2030.

Does livestock protect from malaria or facilitate malaria prevalence? A cross-sectional study in endemic rural areas of Indonesia.

BACKGROUND: Ever since it was discovered that zoophilic vectors can transmit malaria, zooprophylaxis has been used to prevent the disease. However, zoopotentiation has also been observed. Thus, the presence of livestock has been widely accepted as an important variable for the prevalence and risk of malaria, but the effectiveness of zooprophylaxis remained subject to debate. This study aims to critically analyse the effects of the presence of livestock on malaria prevalence using a large dataset from Indonesia. METHODS: This study is based on data from the Indonesia Basic Health Research ("Riskesdas") cross-sectional survey of 2007 organized by the National Institute of Health Research and Development of Indonesia's Ministry of Health. The subset of data used in the present study included 259,885 research participants who reside in the rural areas of 176 regencies throughout the 15 provinces of Indonesia where the prevalence of malaria is higher than the national average. The variable "existence of livestock" and other independent demographic, social and behavioural variables were tested as potential determinants for malaria prevalence by multivariate logistic regressions. RESULTS: Raising medium-sized animals in the house was a significant predictor of malaria prevalence (OR = 2.980; 95% CI 2.348-3.782, P < 0.001) when compared to keeping such animals outside of the house (OR = 1.713; 95% CI 1.515-1.937, P < 0.001). After adjusting for gender, age, access to community health facility, sewage canal condition, use of mosquito nets and insecticide-treated bed nets, the participants who raised medium-sized animals inside their homes were 2.8 times more likely to contract malaria than respondents who did not (adjusted odds ratio = 2.809; 95% CI 2.207-3.575; P < 0.001). CONCLUSIONS: The results of this study highlight the importance of livestock for malaria transmission, suggesting that keeping livestock in the house contributes to malaria risk rather than prophylaxis in Indonesia. Livestock-based interventions should therefore play a significant role in the implementation of malaria control programmes, and focus on households with a high proportion of medium-sized animals in rural areas. The implementation of a "One Health" strategy to eliminate malaria in Indonesia by 2030 is strongly recommended.

Spatial modelling of malaria cases associated with environmental factors in South Sumatra, Indonesia.

BACKGROUND: Malaria, a parasitic infection, is a life-threatening disease in South Sumatra Province, Indonesia. This study aimed to investigate the spatial association between malaria occurrence and environmental risk factors. METHODS: The number of confirmed malaria cases was analysed for the year 2013 from the routine reporting of the Provincial Health Office of South Sumatra. The cases were spread over 436 out of 1613 villages. Six potential ecological predictors of malaria cases were analysed in the different regions using ordinary least square (OLS) and geographically weighted regression (GWR). The global pattern and spatial variability of associations between malaria cases and the selected potential ecological predictors was explored. RESULTS: The importance of different environmental and geographic parameters for malaria was shown at global and village-level in South Sumatra, Indonesia. The independent variables altitude, distance from forest, and rainfall in global OLS were significantly associated with malaria cases. However, as shown by GWR model and in line with recent reviews, the relationship between malaria and environmental factors in South Sumatra strongly varied spatially in different regions. CONCLUSIONS: A more in-depth understanding of local ecological factors influencing malaria disease as shown in present study may not only be useful for developing sustainable regional malaria control programmes, but can also benefit malaria elimination efforts at village level.

Knowledge, attitude, and practice regarding dengue virus infection among inhabitants of Aceh, Indonesia: a cross-sectional study.

BACKGROUND: The Indonesian region of Aceh was the area most severely affected by the earthquake and tsunami of 26 December 2004. Department of Health data reveal an upward trend of dengue cases in Aceh since the events of the tsunami. Despite the increasing incidence of dengue in the region, there is limited understanding of dengue among the general population of Aceh. The aim of this study was to assess the knowledge, attitude, and practice (KAP) regarding dengue among the people of Aceh, Indonesia in order to design intervention strategies for an effective dengue prevention program. METHODS: A community-based cross-sectional study was conducted in Aceh between November 2014 and March 2015 with a total of 609 participants living in seven regencies and two municipalities. Information on the socio-demographic characteristics of participants and their KAP regarding dengue was collected using a pre-tested structured questionnaire. The KAP status (good vs. poor) of participants with different socio-demographic characteristics was compared using Chi Square-test, ANOVA or Fisher's exact test as appropriate. Logistic regression analysis was used to determine the predictors of each KAP domain. RESULTS: We found that 45% of participants had good knowledge regarding dengue and only 32% had good attitudes and good dengue preventive practices. There was a significant positive correlation between knowledge and attitudes, knowledge and practice, and attitudes and practice. In addition, people who had good knowledge were 2.7 times more likely to have good attitudes, and people who had good attitudes were 2.2 times more likely to have good practices regarding dengue. The level of education, occupation, marital status, monthly income, socioeconomic status (SES) and living in the city were associated with the knowledge level. Occupation, SES, and having experienced dengue fever were associated with attitudes. Education, occupation, SES and type of residence were associated with preventive practices. CONCLUSION: Our study suggests that dengue prevention programs are required to increase KAP levels regarding dengue in the communities of Aceh.

DENGUE PREVENTION: CONFIRMATORY FACTOR ANALYSIS OF RELATIONSHIPS BETWEEN ECONOMIC STATUS, KNOWLEDGE, ATTITUDES AND PRACTICE, VACCINE ACCEPTANCE AND WILLINGNESS TO PARTICIPATE IN A STUDY.

The aim of this study was to study the relationships between economic status, knowledge, attitude and practice regarding dengue fever (DF), attitude towards vaccination against dengue virus infection, willingness to participate in a study on dengue, and acceptance of a dengue vaccine. Information on variables of interest was collected in questionnaire-assisted interviews during a communitybased cross-sectional survey conducted in Aceh, Indonesia. A proposed relationship model was tested using Confirmatory Factor Analysis (CFA), and an Exploratory Factor Analysis (EFA) was used to reconstruct an alternative relationship model among variables. Our proposed relationship model differed from the result of the EFA. The CFA indicated that knowledge and attitudes towards DF had the strongest relationship. We also found several direct relationships between sets of variables: a) economic status and knowledge on DF, b) economic status and practices regarding DF, c) knowledge and practices regarding DF, d) attitudes towards DF and dengue vaccine acceptance, as well as e) attitudes towards vaccination and dengue vaccine acceptance. There was no relationship between economic status and dengue vaccine acceptance. In conclusion, our model suggested that the most suitable factor to be targeted for improving dengue prevention was knowledge about DF. In addition, improving attitudes towards vaccination seemed to be the most appropriate effort to increase public acceptance of a dengue vaccine.

Standardized Laboratory Feeding of Larval Aedes japonicus japonicus (Diptera: Culicidae).

The Asian bush mosquito (Aedes japonicus japonicus, Theobald 1901) is an invasive culicid species which originates in Asia but is nowadays present in northern America and Europe. It is a competent vector for several human disease pathogens. In addition to the public health threat, this invasive species may also be an ecological threat for native container-breeding mosquitoes which share a similar larval habitat. Therefore, it is of importance to gain knowledge on ecological and eco-toxicological features of the Asian bush mosquito. However, optimal laboratory feeding conditions have not yet been established. Standardized feeding methods will be needed in assessing the impact of insecticides or competitional strength of this species. To fill this gap, we performed experiments on food quality and quantity for Ae. j. japonicus larvae. We found out that the commercial fish food TetraMin (Tetra, Melle, Germany) in a dose of 10 mg per larva is the most suitable food tested. We also suggest a protocol with a feeding sequence of seven portions for all larval stages of this species.

A multicomponent strategy to improve the availability of antivenom for treating snakebite envenoming.

Snakebite envenoming is a common but neglected public health problem, particularly in impoverished rural regions of sub-Saharan Africa, Asia and Latin America. The only validated treatment for this condition is passive immunotherapy with safe and effective animal-derived antivenoms. However, there is a long-lasting crisis in the availability of these life-saving medications, particularly in sub-Saharan Africa and parts of Asia. We herein advocate a multicomponent strategy to substantially improve the availability of safe and effective antivenoms at the global level. This strategy is based on: (i) preparing validated collections of representative venom pools from the most medically dangerous snakes in high-risk regions of the world; (ii) strengthening the capacity of national antivenom manufacturing and quality control laboratories and their regulatory authorities and establishing new facilities in developing countries through technology transfer, as an integral part of efforts to develop their biological products industry; (iii) getting established laboratories to generate antivenoms for various regions of the world; and (iv) getting governments and relevant organizations to give snakebite envenoming due recognition within national and international public health policy frameworks. These ways of making antivenom available should be complemented by actions to improve health information systems, the accessibility of antivenoms, the training of medical and nursing staff, and community-based education. Such a multicomponent strategy involving stakeholders on many levels could help consolidate sustainable improvements in antivenom availability worldwide.

L'envenimation par morsure de serpent est un problème de santé publique fréquent, mais négligé, en particulier dans les régions rurales pauvres de l'Afrique subsaharienne, de l'Asie et de l'Amérique latine. Le seul traitement validé pour soigner cet état est l'immunothérapie passive avec des sérums antivenimeux d'origine animale sûrs et efficaces. Cependant, une crise durable limite actuellement la disponibilité de ces médicaments vitaux, surtout en Afrique subsaharienne et dans certaines parties de l'Asie. Nous préconisons ici une stratégie à composants multiples pour améliorer considérablement la disponibilité des sérums antivenimeux sûrs et efficaces à l'échelle mondiale. Cette stratégie repose sur: (i) la préparation de collections validées de groupes représentatifs de venins prélevés sur les serpents les plus dangereux sur le plan médical dans les régions à haut risque du monde; (ii) le renforcement de la capacité de production nationale des sérums antivenimeux, des laboratoires de contrôle qualité et de leurs organismes de réglementation, et la création de nouvelles installations dans les pays en développement par transfert de technologies, en tant que partie intégrante de la stratégie de développement de leur industrie de produits biologiques; (iii) la production par les laboratoires déjà établis de sérums antivenimeux pour les différentes régions du monde; et (iv) la reconnaissance officielle par les gouvernements et les organisations compétentes de l'envenimation par morsure de serpent dans le cadre des politiques de santé publique nationales et internationales. Ces façons de rendre disponibles les sérums antivenimeux devraient être complétées par des actions visant à améliorer les systèmes d'informations sanitaires, l'accessibilité des sérums antivenimeux, la formation du personnel médical et infirmier et les programmes communautaires d'éducation. Une telle stratégie à composants multiples impliquant des acteurs à différents niveaux pourrait contribuer à consolider les améliorations durables en matière de disponibilité des sérums antivenimeux dans le monde entier.

El envenenamiento por mordedura de serpiente es un problema de salud pública común pero desatendido, especialmente en las regiones rurales más pobres de África subsahariana, Asia y América Latina. El único tratamiento reconocido contra estas mordeduras es la inmunoterapia pasiva con sueros antiofídicos de origen animal seguros y eficaces. Sin embargo, la disponibilidad de estos medicamentos esenciales para salvar vidas lleva mucho tiempo en crisis, en particular en África subsahariana y en algunas zonas de Asia. En el presente documento, abogamos por una estrategia multicomponente para mejorar de forma sustancial la disponibilidad de sueros antiofídicos seguros y eficaces en todo el mundo. La estrategia se basa en: (i) preparar colecciones reconocidas de sueros antiofídicos representativos de las serpientes más peligrosas en zonas de alto riesgo del mundo; (ii) reforzar la capacidad nacional de producción de sueros antiofídicos y la calidad de los laboratorios de control y sus autoridades normativas, así como crear instalaciones nuevas en los países en desarrollo por medio de la transferencia de tecnología como parte integral de los esfuerzos por desarrollar su industria de productos biológicos; (iii) conseguir que los laboratorios consolidados fabriquen sueros antiofídicos para varias regiones del mundo; y (iv) conseguir que los gobiernos y las organizaciones pertinentes otorguen al envenenamiento por mordedura de serpiente el reconocimiento debido dentro del marco de las políticas nacionales e internacionales de salud pública. Estas tareas dirigidas a facilitar el suero antiofídico deben complementarse con acciones para mejorar los sistemas de información sobre la salud, la accesibilidad de los antiofídicos, la formación del personal médico y de enfermería, y la educación comunitaria. Una estrategia multicomponente de ese tipo, que incluye a los interesados a varios niveles, podría ayudar a consolidar mejoras sostenibles en la disponibilidad de antiofídicos en todo el mundo.

Malaria control in Nepal 1963-2012: challenges on the path towards elimination.

BACKGROUND: Malaria is still a priority public health problem of Nepal where about 84% of the population are at risk. The aim of this paper is to highlight the past and present malaria situation in this country and its challenges for long-term malaria elimination strategies. METHODS: Malariometric indicator data of Nepal recorded through routine surveillance of health facilities for the years between 1963 and 2012 were compiled. Trends and differences in malaria indicator data were analysed. RESULTS: The trend of confirmed malaria cases in Nepal between 1963 and 2012 shows fluctuation, with a peak in 1985 when the number exceeded 42,321, representing the highest malaria case-load ever recorded in Nepal. This was followed by a steep declining trend of malaria with some major outbreaks. Nepal has made significant progress in controlling malaria transmission over the past decade: total confirmed malaria cases declined by 84% (12,750 in 2002 vs 2,092 in 2012), and there was only one reported death in 2012. Based on the evaluation of the National Malaria Control Programme in 2010, Nepal recently adopted a long-term malaria elimination strategy for the years 2011-2026 with the ambitious vision of a malaria-free Nepal by 2026. However, there has been an increasing trend of Plasmodium falciparum and imported malaria proportions in the last decade. Furthermore, the analysis of malariometric indicators of 31 malaria-risk districts between 2004 and 2012 shows a statistically significant reduction in the incidence of confirmed malaria and of Plasmodium vivax, but not in the incidence of P. falciparum and clinically suspected malaria. CONCLUSIONS: Based on the achievements the country has made over the last decade, Nepal is preparing to move towards malaria elimination by 2026. However, considerable challenges lie ahead. These include especially, the need to improve access to diagnostic facilities to confirm clinically suspected cases and their treatment, the development of resistance in parasites and vectors, climate change, and increasing numbers of imported cases from a porous border with India. Therefore, caution is needed before the country embarks towards malaria elimination.

Spatio-temporal distribution of malaria and its association with climatic factors and vector-control interventions in two high-risk districts of Nepal.

BACKGROUND: Over the last decade, the incidence of confirmed malaria has declined significantly in Nepal. The aim of this paper is to assess the spatio-temporal distribution of malaria and its association with climatic factors and vector control interventions in two high-risk districts of Nepal. METHODS: Hotspot analysis was used to visualize the spatio-temporal variation of malaria incidence over the years at village level and generalized additive mixed models were fitted to assess the association of malaria incidence with climatic variables and vector control interventions. RESULTS: Opposing trends of malaria incidence were observed in two high-risk malaria districts of eastern and far-western Nepal after the introduction of long-lasting insecticidal nets (LLINs). The confirmed malaria incidence was reduced from 2.24 per 10,000 in 2007 to 0.31 per 10,000 population in 2011 in Morang district but increased from 3.38 to 8.29 per 10,000 population in Kailali district. Malaria hotspots persisted mostly in the same villages of Kailali district, whereas in Morang district malaria hotspots shifted to new villages after the introduction of LLINs. A 1° C increase in minimum and mean temperatures increased malaria incidence by 27% (RR =1.27, 95% CI =1.12-1.45) and 25% (RR =1.25, 95% CI =1.11-1.43), respectively. The reduction in malaria incidence was 25% per one unit increase of LLINs (RR =0.75, 95% CI =0.62-0.92). The incidence of malaria was 82% lower in Morang than in Kailali district (RR =0.18, 95% CI =0.11-0.33). CONCLUSIONS: The study findings suggest that LLIN coverage should be scaled up to entire districts rather than high-incidence foci only. Climatic factors should be considered for malaria micro-stratification, mosquito repellents should be prescribed for those living in forests, forest fringe and foothills and have regular visits to forests, and imported cases should be controlled by establishing fever check posts at border crossings.

Combining species distribution models and big datasets may provide finer assessments of snakebite impacts.

BACKGROUND: Snakebite is a major poverty-related neglected tropical disease. An integrated scientific approach is needed to understand the dynamics of this important health issue. Our objective was to estimate snakebite occurrence in a tropical area by using a blend of ecological modelling and robust statistical analysis. METHODS: The present study used climatic, environmental, and human population density data to determine the area with snakebite occurrence-probability for the first time in Bangladesh. We also analysed a large, 16-year dataset of hospitalized snakebite cases to reveal the epidemiology of snakebite in the south-eastern zone of the country. FINDINGS: Our results show that cobra bite is the most commonly occurring venomous snakebite in humans (around ~12% of the total yearly snakebite records), and men are more frequently bitten than women (2/3 of human victims are men). Most bites occur during the rainy season for cobra and green pit viper, while krait bites are not restricted to any particular season. As snakebite incidents are closely related to climate conditions, we can model snakebite risk using temperature and precipitation variables. Whereas there is a lack of snakebite reports from several parts of the study area in official records, our models predict that the entire study area is favourable for snakebite incidents. Based on the combined evidence we estimate that about 200,000 snakebite events occur every year in the south-eastern part of Bangladesh alone. Considering future global climate change, our model projections show that snakebite incidence in Bangladesh might not significantly decrease in the future (- 2070-); however, the distribution of probabilities might change, with a predicted increase of snakebite incidence in the hilly areas of the country. CONCLUSIONS: Using climatic data to predict snakebite incidence in Bangladesh allowed us to provide estimations of the total annual number of snakebite cases in the study area. As in most countries, the scarcity of accurate epidemiological data in official records might have masked the real magnitude of this problem. Our analysis suggests that the problem of snakebite envenoming in Bangladesh might be worse than currently perceived. A long-term sustainable snakebite program plan should be designed and institutionalized, considering climatic, geographical and human demographic variables, to obtain better data and facilitate the implementation of accurate snakebite management programs for this country.

Appropriate larval food quality and quantity for Aedes albopictus (Diptera: Culicidae).

The Asian tiger mosquito Aedes albopictus (Skuse, 1894) is a globally invasive prominent vector of viral and parasitic pathogens. To soundly guide insecticide use in control programs it is crucial to use standardized test systems under rigorously controlled environmental conditions that allow for comparisons across laboratories. An acute standard test procedure (24 h) for insecticide resistance monitoring of mosquitoes has been published by the World Health Organization in 1998, but a standardized chronic test to monitor sublethal insecticide effects on the life cycle of mosquitoes does not yet exist. As a first step toward a standardized chronic bioassay (half-life-cycle-test), the exclusion of qualitative and quantitative food effects by means of standardized, optimal larval feeding would greatly facilitate inter-laboratory comparisons. Against this background we evaluated food qualities and quantities for the aquatic part of the A. albopictus life cycle under different thermal conditions. Five mg TetraMin (Tetra, Melle, Germany) larva(-1) at 25 degrees C rendered the lowest mortality and large pupae. Our fundamental data on A. albopictus feeding provide an opportunity to standardize experiments and thus support interlaboratory comparisons of studies on the ecotoxicology of this dangerous vector mosquito.

Survey on sea snakebite and related morbidity and mortality among Bangladeshi fishermen in the Bay of Bengal: A pilot study.

Around two million people are engaged in marine fishing in the Bay of Bengal. Bites by sea snakes were common hazards feared by millions fishing at sea in earlier days. Current morbidity and mortality are also not known. This study was conducted to document and describe sea snake bites among selected communities of sea-going fishermen in Bangladesh. A questionnaire-based cross-sectional survey was conducted from May to October 2019 among three communities of sea-going fishermen living along the coast of the Bay of Bengal in Cox's Bazar district. Fishermen were first asked by trained interviewers to recall any sea snakebites to themselves and among their fellows on board within the last year, then within the last 5 years and at any time before that. For any bite, related information including outcome was noted. Overall, 25.4% of respondents (62 out of 244) had been bitten by sea-snakes. Mean age was 37.6(±14) years; all males. 51.6% received some sort of treatment locally; 71% hot compress and 48% tourniquets. In 80.6% the affected limb was not immobilized. The bitten site was incised in 29%. 22.6% received treatment from traditional healers, 48.4% from local hospitals, 29% from district hospital. Six victims (9.7%) suffered from severe life-threatening consequences of the sea snakebite but none died. 32% of the fishermen had seen the offending snake. Sea snakebites are potentially dangerous; therefore, educating fishermen to avoid contact with sea snakes would dramatically reduce the incidence of sea snakebites. Most bites are treated initially by local measures which are often not scientific. Provision of proper first aid and treatment might reduce mortality and morbidity. A larger survey on sea snake bites among the fishermen in all coastal areas of Bangladesh is needed to determine the nationwide burden of morbidity and mortality related to sea snakebite.

Hospital admissions due to snake envenomation in the Republic of Cyprus: a 7-year retrospective review.

BACKGROUND: Snake envenomation is a major neglected tropical disease, lacking data in many countries including Cyprus, a Mediterranean island inhabited by the medically important blunt-nosed viper (Macrovipera lebetina). Reviewing the 2013-2019 period, we present first-time epidemiological snakebite data in the Republic of Cyprus. METHODS: We obtained data on snake envenomation-related hospital admissions from the Ministry of Health, and population and rainfall data from the Statistical Service of Cyprus and Department of Meteorology websites. Human-viper conflict information was acquired from interviews with 12 representatives of Cypriot institutions. RESULTS: Between 2013 and 2019, 288 snake envenomation cases were admitted to public hospitals, averaging 41 people annually. The minimum was 29 cases (2017) and the maximum was 58 (2015). Snake envenomation incidence increased from 4.55 per 100,000 population (2013) to 6.84 (2015), but remained low since 2017 (3.49 in 2019). Between 2000 and 2018, the deaths of one man (73 years), and indirectly, one woman (77 years), were related to snake envenomation. While 266 cases (92%) happened between April and October (the blunt-nosed viper activity period), most envenomations occurred in September (cumulative for 2013-2019), with 88 cases (31%). Snakebite incidence peaked in the 60-69 years age group (9.19 per 100,000 population), and was higher in males (6.85) than in females (2.82). Of all admitted patients, 242 (84%) were discharged within 4 days. Mean hospital stay duration was 2.65 days, with one case of 13 days. Most patients were admitted to the general hospitals in Paphos (51%), Limassol (30%) and Nicosia (11%), which provide secondary healthcare, with the last one providing tertiary healthcare. CONCLUSIONS: Snakebite-related deaths are very rare in the Republic of Cyprus. Most envenomation cases happened in late summer (September). Short hospital stays indicate mostly non-severe clinical courses. The hospital admission data suggest that snake envenomation risk is highest in Paphos district. The statistical data hint at males and middle- to older-aged people being at highest risk, whereas from our interview data we assume that outdoor workers are at higher risk than other occupational groups.

Prevalence and risk factors associated with chronic kidney disease in Nepal: evidence from a nationally representative population-based cross-sectional study.

OBJECTIVE: This study aimed to determine population-based prevalence of chronic kidney disease (CKD) and its associated factors in Nepal. STUDY DESIGN: The study was a nationwide population-based cross-sectional study. SETTING AND PARTICIPANTS: Cross-sectional survey conducted in a nationally representative sample of 12 109 Nepalese adult from 2016 to 2018 on selected chronic non-communicable diseases was examined. Multistage cluster sampling with a mix of probability proportionate to size and systematic random sampling was used for the selection of individuals aged 20 years and above. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome in this study was population-based prevalence of CKD in Nepal. A participant was considered to have CKD if the urine albumin-to-creatinine ratio was greater than or equal to 30 mg/g and/or estimated glomerular filtration rate is less than 60 mL/min/1.73 m2 at baseline and in follow-up using modification of diet in renal disease study equations. The secondary outcome measure was factors associated with CKD in Nepal. The covariate adjusted association of risk factors and CKD was calculated using multivariable binary logistic regression. RESULTS: The overall prevalence of CKD in Nepal was 6.0% (95% CI 5.5 to 6.6). Factors independently associated with CKD included older age (adjusted OR (AOR) 2.6, 95% CI 1.9 to 3.6), Dalit caste (AOR 1.6, 95% CI 1.1 to 2.3), hypertension (AOR 2.4, 95% CI 2.0 to 3.0), diabetes mellitus (AOR 3.2, 95% CI 2.5 to 4.1), raised total cholesterol (AOR 1.3, 95% CI 1.0 to 1.6) and increased waist-to-hip ratio (AOR 1.6, 95% CI 1.2 to 2.3). CONCLUSION: This nationally representative study shows that the prevalence of CKD in the adult population of Nepal is substantial, and it is independently associated with several cardiometabolic traits. These findings warrant longitudinal studies to identify the causes of CKD in Nepal and effective strategies to prevent it.

Functional hypervariability and gene diversity of cardioactive neuropeptides.

Crustacean cardioactive peptide (CCAP) and related peptides are multifunctional regulatory neurohormones found in invertebrates. We isolated a CCAP-related peptide (conoCAP-a, for cone snail CardioActive Peptide) and cloned the cDNA of its precursor from venom of Conus villepinii. The precursor of conoCAP-a encodes for two additional CCAP-like peptides: conoCAP-b and conoCAP-c. This multi-peptide precursor organization is analogous to recently predicted molluscan CCAP-like preprohormones, and suggests a mechanism for the generation of biological diversification without gene amplification. While arthropod CCAP is a cardio-accelerator, we found that conoCAP-a decreases the heart frequency in Drosophila larvae, demonstrating that conoCAP-a and CCAP have opposite effects. Intravenous injection of conoCAP-a in rats caused decreased heart frequency and blood pressure in contrast to the injection of CCAP, which did not elicit any cardiac effect. Perfusion of rat ventricular cardiac myocytes with conoCAP-a decreased systolic calcium, indicating that conoCAP-a cardiac negative inotropic effects might be mediated via impairment of intracellular calcium trafficking. The contrasting cardiac effects of conoCAP-a and CCAP indicate that molluscan CCAP-like peptides have functions that differ from those of their arthropod counterparts. Molluscan CCAP-like peptides sequences, while homologous, differ between taxa and have unique sequences within a species. This relates to the functional hypervariability of these peptides as structure activity relationship studies demonstrate that single amino acids variations strongly affect cardiac activity. The discovery of conoCAPs in cone snail venom emphasizes the significance of their gene plasticity to have mutations as an adaptive evolution in terms of structure, cellular site of expression, and physiological functions.

The greater black krait (Bungarus niger), a newly recognized cause of neuro-myotoxic snake bite envenoming in Bangladesh.

Prospective studies of snake bite patients in Chittagong, Bangladesh, included five cases of bites by greater black kraits (Bungarus niger), proven by examination of the snakes that had been responsible. This species was previously known only from India, Nepal, Bhutan and Burma. The index case presented with descending flaccid paralysis typical of neurotoxic envenoming by all Bungarus species, but later developed generalized rhabdomyolysis (peak serum creatine kinase concentration 29,960 units/l) with myoglobinuria and acute renal failure from which he succumbed. Among the other four patients, one died of respiratory paralysis in a peripheral hospital and three recovered after developing paralysis, requiring mechanical ventilation in one patient. One patient suffered severe generalized myalgia and odynophagia associated with a modest increase in serum creatine kinase concentration. These are the first cases of Bungarus niger envenoming to be reported from any country. Generalized rhabdomyolysis has not been previously recognized as a feature of envenoming by any terrestrial Asian elapid snake, but a review of the literature suggests that venoms of some populations of Bungarus candidus and Bungarus multicinctus in Thailand and Vietnam may also have this effect in human victims. To investigate this unexpected property of Bungarus niger venom, venom from the snake responsible for one of the human cases of neuro-myotoxic envenoming was injected into one hind limb of rats and saline into the other under buprenorphine analgesia. All animals developed paralysis of the venom-injected limb within two hours. Twenty-four hours later, the soleus muscles were compared histopathologically and cytochemically. Results indicated a predominantly pre-synaptic action (ß-bungarotoxins) of Bungarus niger venom at neuromuscular junctions, causing loss of synaptophysin and the degeneration of the terminal components of the motor innervation of rat skeletal muscle. There was oedema and necrosis of extrafusal muscle fibres in envenomed rat soleus muscles confirming the myotoxic effect of Bungarus niger venom, attributable to phospholipases A2. This study has demonstrated that Bungarus niger is widely distributed in Bangladesh and confirms the risk of fatal neuro-myotoxic envenoming, especially as no specific antivenom is currently manufactured. The unexpected finding of rhabdomyolysis should prompt further investigation of the venom components responsible. The practical implications of having to treat patients with rhabdomyolysis and consequent acute renal failure, in addition to the more familiar respiratory failure associated with krait bite envenoming, should not be underestimated in a country that is poorly equipped to deal with such emergencies.