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Diagnosing and treating acute severe and recurrent antivenom-related anaphylaxis (ARA) is challenging and reported experience is limited. Herein, we describe our experience of severe ARA in patients with neurotoxic snakebite envenoming in Nepal. Patients were enrolled in a randomised, double-blind trial of high vs. low dose antivenom, given by intravenous (IV) push, followed by infusion. Training in ARA management emphasised stopping antivenom and giving intramuscular (IM) adrenaline, IV hydrocortisone, and IV chlorphenamine at the first sign/s of ARA. Later, IV adrenaline infusion (IVAI) was introduced for patients with antecedent ARA requiring additional antivenom infusions. Preantivenom subcutaneous adrenaline (SCAd) was introduced in the second study year (2012). Of 155 envenomed patients who received ≥ 1 antivenom dose, 13 (8.4%), three children (aged 5−11 years) and 10 adults (18−52 years), developed clinical features consistent with severe ARA, including six with overlapping signs of severe envenoming. Four and nine patients received low and high dose antivenom, respectively, and six had received SCAd. Principal signs of severe ARA were dyspnoea alone (n=5 patients), dyspnoea with wheezing (n=3), hypotension (n=3), shock (n=3), restlessness (n=3), respiratory/cardiorespiratory arrest (n=7), and early (n=1) and late laryngeal oedema (n=1); rash was associated with severe ARA in 10 patients. Four patients were given IVAI. Of the 8 (5.1%) deaths, three occurred in transit to hospital. Severe ARA was common and recurrent and had overlapping signs with severe neurotoxic envenoming. Optimising the management of ARA at different healthy system levels needs more research. This trial is registered with NCT01284855.
Zika virus (ZIKV) infection, a public health emergency of international concern, has recently been confirmed in Indonesia. However, to date, there has been no study to assess how prepared healthcare workers in Indonesia are to confront this emerging infectious disease. The aim of this study was to assess the attitudes of medical doctors in Indonesia towards ZIKV infection and its associated explanatory variables. A cross-sectional self-administered online survey was conducted from 3 May to 3 June 2016 in Aceh province, Indonesia. A pre-tested questionnaire was used to collect data on doctors’ attitudes towards ZIKV infection and a range of explanatory variables (basic demographic data, professional characteristics, workplace characteristics and facilities, and medical experience related to ZIKV infection). Associations between attitude and explanatory variables were assessed using multiple-step logistic regression. We received 631 responses, 424 (67.19%) of which were included in the final analysis. Approximately 64% (271) of doctors had a poor attitude towards ZIKV infection. Experience considering ZIKV infection as a differential diagnosis and attendance at a national conference was associated with a good attitude, with odds ratios (OR) of 3.93 (95% confidence interval [CI]: 1.15–13.49) and 1.69 (95% CI: 1.03–2.76), respectively. Unexpectedly, doctors who had attended an international conference and those working at places that had molecular diagnostic (polymerase chain reaction based testing) facilities had lower odds of having a good attitude (OR: 0.35 [95% CI: 0.15–0.84] and 0.42 [95% CI: 0.19–0.95], respectively). In conclusion, the attitude towards ZIKV infection is relatively poor among doctors in Aceh. Therefore, strategies for enhancing their capacity to respond to ZIKV infection are needed. The survey concept and tools were well accepted by the participants of this study, suggesting that this rapid assessment could be rolled out across the Indonesian archipelago and elsewhere to identify and regionally differentiate unmet needs of disease and outbreak preparedness.
We describe 70 cases of monocled cobra (Naja kaouthia) bite admitted to Chittagong Medical College Hospital, Bangladesh. The biting snakes were identified by examining the dead snake and/or detecting N. kaouthia venom antigens in patients' serum. Bites were most common in the early morning and evening during the monsoon (May-July). Ligatures were routinely applied to the bitten limb before admission. Thirty-seven patients consulted traditional healers, most of whom made incisions around the bite site. Fifty-eight patients experienced severe neurotoxicity and most suffered swelling and pain of the bitten limb. The use of an Indian polyvalent antivenom in patients exhibiting severe neurotoxicity resulted in clinical improvement but most patients experienced moderate-to-severe adverse reactions. Antivenom did not influence local blistering and necrosis appearing in 19 patients; 12 required debridement. Edrophonium significantly improved the ability of patients to open the eyes, endurance of upward gaze, and peak expiratory flow rate suggesting that a longer-acting anticholinesterase drug (neostigmine) could be recommended for first aid. The study suggested that regionally appropriate antivenom should be raised against the venoms of the major envenoming species of Bangladesh and highlighted the need to improve the training of staff of local medical centers and to invest in the basic health infrastructure in rural communities.
Observed weather and projected climate change suggest an increase in the transmission of vector-borne diseases (VBDs) in the Hindu Kush Himalayan (HKH) region. In this study, we systematically explore the literature for empiric associations between the climate variables and specific VBDs and their vectors in the HKH region. We conducted a systematic synthesis of the published literature on climate variables, VBDs and vectors in the HKH region until the 8th of December 2020. The majority of studies show significant positive associations of VBDs with climatic factors, such as temperature, precipitation, relative humidity, etc. This systematic review allowed us to identify the most significant variables to be considered for evidence-based trend estimates of the effects of climate change on VBDs and their vectors in the HKH region. This evidence-based trend was set into the context of climate change as well as the observed expansion of VBDs and disease vectors in the HKH region. The geographic range of VBDs expanded into previously considered non-endemic areas of highlands (mountains) in the HKH region. Based on scarce, but clear evidence of a positive relationship of most climate variables and VBDs and the observed climatic changes, we strongly recommend an expansion of vector control and surveillance programmes in areas of the HKH region that were previously considered to be non-endemic.
Background: Despite its largely mountainous terrain for which this Himalayan country is a popular tourist destination, Nepal is now endemic for five major vector-borne diseases (VBDs), namely malaria, lymphatic filariasis, Japanese encephalitis, visceral leishmaniasis and dengue fever. There is increasing evidence about the impacts of climate change on VBDs especially in tropical highlands and temperate regions. Our aim is to explore whether the observed spatiotemporal distributions of VBDs in Nepal can be related to climate change.
Methodology: A systematic literature search was performed and summarized information on climate change and the spatiotemporal distribution of VBDs in Nepal from the published literature until December 2014 following providing items for systematic review and meta-analysis (PRISMA) guidelines.
Principal findings: We found 12 studies that analysed the trend of climatic data and are relevant for the study of VBDs, 38 studies that dealt with the spatial and temporal distribution of disease vectors and disease transmission. Among 38 studies, only eight studies assessed the association of VBDs with climatic variables. Our review highlights a pronounced warming in the mountains and an expansion of autochthonous cases of VBDs to non-endemic areas including mountain regions (i.e., at least 2,000 m above sea level). Furthermore, significant relationships between climatic variables and VBDs and their vectors are found in short-term studies.
Conclusion: Taking into account the weak health care systems and difficult geographic terrain of Nepal, increasing trade and movements of people, a lack of vector control interventions, observed relationships between climatic variables and VBDs and their vectors and the establishment of relevant disease vectors already at least 2,000 m above sea level, we conclude that climate change can intensify the risk of VBD epidemics in the mountain regions of Nepal if other non-climatic drivers of VBDs remain constant.
Background: Dengue virus infection is the most rapidly spreading vector-borne disease in the world. Essential research on dengue virus transmission and its prevention requires community participation. Therefore, it is crucial to understand the factors that are associated with the willingness of communities in high prevalence areas to participate in dengue research. The aim of this study was to explore factors associated with the willingness of healthy community members in Aceh province, Indonesia, to participate in dengue research that would require phlebotomy.
Methodology/Principal Findings: A community-based cross-sectional study was carried out in nine regencies and municipalities of Aceh from November 2014 to March 2015. Interviews using a set of validated questionnaires were conducted to collect data on demography, history of dengue infection, socioeconomic status, and knowledge, attitude and practice regarding dengue fever. Two-step logistic regression and Spearman’s rank correlation (rs) analysis were used to assess the influence of independent variables on dependent variables. Among 535 participants, less than 20% had a good willingness to participate in the dengue study. The factors associated with good willingness to participate were being female, working as a civil servant, private employee or entrepreneur, having a high socioeconomic status and good knowledge, attitude and practice regarding dengue. Good knowledge and attitude regarding dengue were positive independent predictors of willingness to participate (OR: 2.30 [95% CI: 1.36–3.90] and 3.73 [95% CI: 2.24–6.21], respectively).
Conclusion/Significance: The willingness to participate in dengue research is very low among community members in Aceh, and the two most important associated factors are knowledge and attitude regarding dengue. To increase participation rate, efforts to improve the knowledge and attitude of community members regarding dengue fever and dengue-related research is required before such studies are launched.
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.
Background:Aedes aegypti is a potential vector for several arboviruses including dengue and Zika viruses. The species seems to be restricted to subtropical/tropical habitats and has difficulties in establishing permanent populations in southern Europe, probably due to constraints during the winter season. The aim of this study was to systematically analyze the cold tolerance (CT) of Ae. aegypti in its most cold-resistant life stage, the eggs.
Methods: The CT of Ae. aegypti eggs was compared with that of Ae. albopictus which is well established in large parts of Europe. By systematically studying the literature (meta-analysis), we recognized that CT has been rarely tested in Ae. aegypti eggs, but eggs can survive at zero and sub-zero temperatures for certain exposure periods. To overcome potential bias from experimental differences between studies, we then conducted species comparisons using a harmonized high-resolution CT measuring method. From subtropical populations of the same origin, the survival (hatching in %) and emergence of adults of both species were measured after zero and sub-zero temperature exposures for up to 9 days (3 °C, 0 °C and − 2 °C: ≤ 9 days; − 6 °C: ≤ 2 days).
Results: Our data show that Ae. aegypti eggs can survive low and sub-zero temperatures for a short time period similar to or even better than those of Ae. albopictus. Moreover, after short sub-zero exposures of eggs of both species, individuals still developed into viable adults (Ae. aegypti: 3 adults emerged after 6 days at − 2 °C, Ae. albopictus: 1 adult emerged after 1 day at − 6 °C).
Conclusions: Thus, both the literature and the present experimental data indicate that a cold winter may not be the preventing factor for the re-establishment of the dengue vector Ae. aegypti in southern Europe.
Background: Currently, there is inadequate evidence on which to base clinical management of neurotoxic snakebite envenoming, especially in the choice of initial antivenom dosage. This randomised controlled trial compared the effectiveness and safety of high versus low initial antivenom dosage in victims of neurotoxic envenoming.
Methodology/ Principal findings: This was a balanced, randomised, double-blind trial that was conducted in three health care centers located in the Terai plains of Nepal. Participants received either low (two vials) or high (10 vials) initial dosage of Indian polyvalent antivenom. The primary composite outcome consisted of death, the need for assisted ventilation and worsening/recurrence of neurotoxicity. Hourly evaluations followed antivenom treatment. Between April 2011 and October 2012, 157 snakebite victims were enrolled, of which 154 were analysed (76 in the low and 78 in the high initial dose group). Sixty-seven (43·5%) participants met the primary outcome definition. The proportions were similar in the low (37 or 48.7%) vs. high (30 or 38.5%) initial dose group (difference = 10·2%, 95%CI [-6·7 to 27·1], p = 0·264). The mean number of vials used was similar between treatment groups. Overall, patients bitten by kraits did worse than those bitten by cobras. The occurrence of treatment-related adverse events did not differ among treatment groups. A total of 19 serious adverse events occurred, including seven attributed to antivenom.
Conclusions: This first robust trial investigating antivenom dosage for neurotoxic snakebite envenoming shows that the antivenom currently used in Nepal performs poorly. Although the high initial dose regimen is not more effective than the low initial dose, it offers the practical advantage of being a single dose, while not incurring higher consumption or enhanced risk of adverse reaction. The development of new and more effective antivenoms that better target the species responsible for bites in the region will help improve future patients’ outcomes.
Trial registration: The study was registered on clinicaltrials.gov (NCT01284855) (GJ 5/1)
The Asian tiger mosquito, Aedes albopictus (Diptera: Culicidae, SKUSE), is an important threat to public health due to its rapid spread and its potential as a vector. The eggs of Ae. albopictus are the most cold resistant life stage and thus, the cold hardiness of eggs is used to predict the future occurrence of the species in distribution models. However, the mechanism of cold hardiness has yet to be revealed. To address this question, we analyzed the layers of diapausing and cold acclimatized eggs of a temperate population of Ae. albopictus in a full factorial test design using transmission electron microscopy. We reviewed the hypotheses that a thickened wax layer or chorion is the cause of cold hardiness but found no evidence. As a result of the induced diapause, the thickness of the dark endochorion as a layer of high electron density and thus an assumed location for waxes was decreasing. We therefore hypothesized a qualitative alteration of the wax layer due to compaction. Cold acclimation was causing an increase in the thickness of the middle serosa cuticle indicating a detachment of serosa membrane from the endochorion as a potential adaptation strategy to isolate inoculating ice formations in the inter-membranous space.