Molecular and Entomological Characterization of 2023 Dengue Outbreak in Dhading District, Central Nepal.

In 2023, Nepal faced its second largest dengue outbreak ever, following a record-breaking number of dengue cases in 2022, characterized by the expansion of infections into areas of higher altitudes. However, the characteristics of the 2023 circulating dengue virus (DENV) and the vector density remain poorly understood. Therefore, we performed DENV serotyping, clinical and laboratory assessment, and entomological analysis of the 2023 outbreak in central Nepal. A total of 396 fever cases in Dhading hospital suspected of being DENV positive were enrolled, and blood samples were collected and tested by different techniques including PCR. Of these, 278 (70.2%) had confirmed DENV infection. Multiple serotypes (DENV-1, -2, and -3) were detected. DENV-2 (97.5%) re-emerged after six years in Dhading while DENV-3 was identified for the first time. Dengue inpatients had significantly higher frequency of anorexia, myalgia, rash, diarrhea, nausea, vomiting, abdominal pain, and thrombocytopenia (p < 0.05). In this area, Aedes mosquitoes largely predominated (90.7%) with the majority being A. aegypti (60.7%). We also found high levels of Aedes index (20.0%) and container index (16.7%). We confirmed multiple DENV serotype circulation with serotype re-emergence and new serotype introduction, and high vector density in 2023. These findings call for the urgent initiation and scaling up of DENV molecular surveillance in human and mosquito populations for dengue control and prevention in Nepal.

Anxiety and its risk factors among non-Japanese residents living in Japan undergoing COVID-19 situation: A cross-sectional survey.

INTRODUCTION: In the context of collective efforts taken in Japan to control the spread of COVID-19, the state of emergency and social distancing have caused a negative impact on the mental health of all residents, including foreign communities in Japan. This study aimed to evaluate the level of anxiety and its associated factors among non-Japanese residents residing in Japan during the COVID-19 pandemic. METHODS: A web-based survey in 13 languages was conducted among non-Japanese residents living in Japan during the COVID-19 situation. The State-Trait Anxiety Inventory assessed the level of anxiety-State (STAI-S) scores prorated from its six-item version. The multivariable logistic regression using the Akaike Information Criterion (AIC) method was performed to identify the associated factors of anxiety among participants. RESULTS: From January to March 2021, we collected 392 responses. A total of 357 valid responses were analyzed. 54.6% of participants suffered from clinically significant anxiety (CSA). In multivariable logistic model analysis, the CSA status or the high level of anxiety was associated with three factors, including having troubles/difficulties in learning or working, decreased sleep duration, and decreased overall physical health (p<0.05). CONCLUSION: Our study suggests several possible risk factors of anxiety among non-Japanese residents living in Japan undergoing the COVID-19 pandemic, including the troubles or difficulties in learning or working, the decrease in sleep duration, and the decrease in overall physical health.

Possible high risk of transmission of the Nipah virus in South and South East Asia: a review.

Nipah virus (NiV) is a zoonotic, single-stranded RNA virus from the family Paramyxoviridae, genus Henipavirus. NiV is a biosafety-level-4 pathogen that is mostly spread by Pteropus species, which serve as its natural reservoir host. NiV is one of the major public health challenges in South and South East Asia. However, few molecular studies have been conducted to characterise NiV in a specific region. The main objective of this review is to understand the epidemiology, pathogenesis, molecular surveillance, transmission dynamics, genetic diversity, reservoir host, clinical characteristics, and phylogenetics of NiV. South and South East Asian nations have experienced NiV outbreaks. Phylogenetic analysis confirmed that two primary clades of NiV are in circulation. In humans, NiV causes severe respiratory illness and/or deadly encephalitis. NiV is mainly diagnosed by ELISA along with PCR. Therefore, we recommend that the governments of the region support the One Health approach to reducing the risk of zoonotic disease transmission in their respective countries.

Coinfection and circulation of chikungunya virus and dengue virus in pediatric patients in Myanmar, 2019.

Myanmar is an endemic country for arboviruses, and outbreaks occur frequently. A cross-sectional analytical study was conducted during the peak season of the chikungunya virus (CHIKV) outbreak in 2019. A total of 201 patients with acute febrile illness who were admitted to the 550-bedded Mandalay Children Hospital in Myanmar were enrolled in the study, and virus isolation, serological tests, and molecular tests for the dengue virus (DENV) and CHIKV were performed for all samples. Out of 201 patients, 71 (35.3%) were only DENV-infected, 30 (14.9%) were only CHIKV-infected and 59 (29.4%) were coinfected with DENV and CHIKV. The viremia levels of the DENV- and CHIKV- mono-infected groups were significantly higher than those of the group coinfected with DENV and CHIKV. Genotype I of DENV-1, genotypes I and III of DENV-3, genotype I of DENV-4 and the East/Central/South African genotype of CHIKV were co-circulating during the study period. Two novel epistatic mutations of CHIKV (E1:K211E and E2:V264A) were noted. This study highlighted that there were many coinfection cases during the outbreak and that the co-circulation of both viruses in DENV-endemic regions warrants effective monitoring of these emerging pathogens via comprehensive surveillance to facilitate the implementation of effective control measures.

Co-Circulation of Dengue Virus Serotypes 1, 2, and 3 during the 2022 Dengue Outbreak in Nepal: A Cross-Sectional Study.

The largest dengue outbreak in the history of Nepal occurred in 2022, with a significant number of casualties. It affected all 77 districts, with the nation's capital, Kathmandu (altitude 1300 m), being the hardest hit. However, the molecular epidemiology of this outbreak, including the dengue virus (DENV) serotype(s) responsible for this epidemic, remain unknown. Here, we report the epidemic trends, clinico-laboratory features, and virus serotypes and their viral load profiles that are associated with this outbreak in Nepal. Dengue-suspected febrile patients were investigated by routine laboratory, serological, and molecular tools, including a real-time quantitative polymerase chain reaction (qRT-PCR). Of the 538 dengue-suspected patients enrolled, 401 (74.5%) were diagnosed with dengue. Among these dengue cases, 129 (32.2%) patients who required hospital admission had significant associations with myalgia, rash, diarrhea, retro-orbital pain, bleeding, and abdominal pain. DENV-1, -2, and -3 were identified during the 2022 epidemic, with a predominance of DENV-1 (57.1%) and DENV-3 (32.1%), exhibiting a new serotype addition. We found that multiple serotypes circulated in 2022, with a higher frequency of hospitalizations, more severe dengue, and more deaths than in the past. Therefore, precise mapping of dengue and other related infections through integrated disease surveillance, evaluation of the dynamics of population-level immunity and virus evolution should be the urgent plans of action for evidence-based policy-making for dengue control and prevention in the country.

Forty years (1980-2019) of visceral leishmaniasis in Nepal: trends and elimination challenges.

BACKGROUND: Visceral leishmaniasis (VL) is an important re-emerging neglected tropical disease associated with poverty. Despite the elimination initiative started in 2005, VL cases have been expanding into geographic areas in Nepal. The present study aims at exploring the trends of VL from 1980 to 2019. METHODS: This retrospective analysis covers 40 y of VL cases reported by the Epidemiology Diseases Control Division, Nepal. Subgroup analyses for annual incidence were performed by age, sex, seasons, districts and provinces, and VL cases were visualized on in-country maps. RESULTS: A total of 34 564 cases and 584 deaths of VL were reported during 1980-2019. VL persistently increased until 2006 and was reported from all seven provinces of the country. The highest number of confirmed cases (n=2229) was reported in 2003 and the lowest (n=60) in 1983. VL cases expanded from 12 to 23 endemic districts. The key components of the VL elimination program are early diagnosis; enhanced surveillance; integrated vector management; social mobilization; research and treatment. CONCLUSIONS: Expansion of VL towards the hilly and mountain regions of Nepal has posed challenges to the elimination program. Urgent VL control measures are required to achieve the elimination goals.

SARS-CoV-2 Omicron and its current known unknowns: A narrative review.

The emergence of the SARS-CoV-2 Omicron variant (B.1.1.529) has created great global distress. This variant of concern shows multiple sublineages, importantly B.1.1.529.1 (BA.1), BA.1 + R346K (BA.1.1), and B.1.1.529.2 (BA.2), each with unique properties. However, little is known about this new variant, specifically its sub-variants. A narrative review was conducted to summarise the latest findings on transmissibility, clinical manifestations, diagnosis, and efficacy of current vaccines and treatments. Omicron has shown two times higher transmission rates than Delta and above ten times more infectious than other variants over a similar period. With more than 30 mutations in the spike protein's receptor-binding domain, there is reduced detection by conventional RT-PCR and rapid antigen tests. Moreover, the two-dose vaccine effectiveness against Delta and Omicron variants was found to be approximately 21%, suggesting an urgent need for a booster dose to prevent the possibility of breakthrough infections. However, the current vaccines remain highly efficacious against severe disease, hospitalisation, and mortality. Japanese preliminary lab data elucidated that the Omicron sublineage BA.2 shows a higher illness severity than BA.1. To date, the clinical management of Omicron remains unchanged, except for monoclonal antibodies. Thus far, only Bebtelovimab could sufficiently treat all three sub-variants of Omicron. Further studies are warranted to understand the complexity of Omicron and its sub-variants. Such research is necessary to improve the management and prevention of Omicron infection.

Has COVID-19 suppressed dengue transmission in Nepal?

Following the report of the first COVID-19 case in Nepal on 23 January 2020, three major waves were documented between 2020 and 2021. By the end of July 2022, 986 596 cases of confirmed COVID-19 and 11 967 deaths had been reported and 70.5% of the population had received at least two doses of a COVID-19 vaccine. Prior to the pandemic, a large dengue virus (DENV) epidemic affected 68 out of 77 districts, with 17 932 cases and six deaths recorded in 2019. In contrast, the country's Epidemiology and Disease Control Division reported 530 and 540 dengue cases in the pandemic period (2020 and 2021), respectively. Furthermore, Kathmandu reported just 63 dengue cases during 2020 and 2021, significantly lower than the 1463 cases reported in 2019. Serological assay showed 3.2% positivity rates for anti-dengue immunoglobulin M antibodies during the pandemic period, contrasting with 26.9-40% prior to it. Real-time polymerase chain reaction for DENV showed a 0.5% positive rate during the COVID-19 pandemic which is far lower than the 57.0% recorded in 2019. Continuing analyses of dengue incidence and further strengthening of surveillance and collaboration at the regional and international levels are required to fully understand whether the reduction in dengue incidence/transmission were caused by movement restrictions during the COVID-19 pandemic.

Evaluation of risk factors associated with SARS-CoV-2 transmission.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has caused high morbidity and mortality worldwide. Since there is not enough evidence of risk factors of SARS-CoV-2 transmission, this study aimed to evaluate them. METHODS: This survey-based study was conducted across 66 countries from May to November 2020 among suspected and confirmed individuals with COVID-19. The stepwise AIC method was utilized to determine the optimal multivariable logistic regression to explore predictive factors of SARS-CoV-2 transmission. RESULTS: Among 2372 respondents who participated in the study, there were 1172 valid responses. The profession of non-healthcare-worker (OR: 1.77, 95%CI: 1.04-3.00, p = .032), history of SARS-CoV or MERS-CoV infection (OR: 4.78, 95%CI: 2.34-9.63, p < .001), higher frequency of contact with colleagues (OR: 1.17, 95%CI: 1.01-1.37, p = .041), and habit of hugging when greeting (OR: 1.25, 95%CI: 1.00-1.56, p = .049) were associated with an increased risk of contracting COVID-19. Current smokers had a lower likelihood of having COVID-19 compared to former smokers (OR: 5.41, 95%CI: 1.93-17.49, p = .002) or non-smokers (OR: 3.69, 95%CI: 1.48-11.11, p = .01). CONCLUSIONS: Our study suggests several risk factors for SARS-CoV-2 transmission including the profession of non-healthcare workers, history of other coronavirus infections, frequent close contact with colleagues, the habit of hugging when greeting, and smoking status.

Since there is not enough evidence of risk factors of SARS-CoV-2 transmission, this study aimed to evaluate them. The risk of SARS-CoV-2 infection was higher among non-healthcare workers and among those who had a history of being tested positive for SARS-CoV or MERS-CoV before the COVID-19 outbreak. The habit of frequent contact with colleagues or hugging when greeting significantly increased the risk of being infected with SARS-CoV-2. The current smokers had a lower risk of getting infected with SARS-CoV-2 than others who had a habit of smoking tobacco in the past or who had never smoked.

Association of self-reported allergic rhinitis with dengue severity: A case-control study.

BACKGROUND: The severity of dengue infection has been reportedly associated with patients' allergic reactions. To further elucidate the role of allergy in dengue severity, we conducted a matched case-control study to assess the association between allergic background and dengue shock syndrome. METHODS: This is a matched case-control study that was carried out in the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam from January to December 2017. Dengue infection was determined by non-structure protein 1 (NS1) diagnostic quick test or anti-dengue antibodies (IgM). The total and dengue-specific IgE levels were measured using ELISA. Patients' demographics, clinical, and allergic profiles were collected using a structured questionnaire. RESULTS: A total of 572 dengue patients with positive NS1 (92.7%) or IgM antibodies (7.3%) results were included in this study. Of these patients, 143 patients developed dengue shock syndrome (case group) while the other 429 patients did not (control group). None of the baseline characteristics including age, sex, or being overweight was significantly different between the two groups (p>0.05). In multivariable analysis, having a history of dengue infection (OR=3.35, 95% CI: 1.8-6.17, p<0.001) and allergic rhinitis (OR=1.95, 95% CI: 1.11-3.4, p = 0.019) were found to be associated with dengue shock syndrome. Higher levels of dengue-specific IgE were not associated with worse outcomes in patients with allergies (p = 0.204) or allergic rhinitis (p = 0.284). CONCLUSION: Dengue patients presenting with a history of a previous dengue infection or allergic rhinitis should be considered high-risk patients for the development of dengue shock syndrome.

How an Outbreak of COVID-19 Circulated Widely in Nepal: A Chronological Analysis of the National Response to an Unprecedented Pandemic.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first COVID-19 case was reported in Wuhan, China, in December 2019. In March 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic. The first COVID-19 case in Nepal was reported in January 2020 in a Nepalese man who had returned from Wuhan to Nepal. This study aims to evaluate the government of Nepal's (GoN) response to the COVID-19 pandemic and explore ways to prevent COVID-19 and other pandemic diseases in the future. As of May 2022, a total of 979,140 cases and 11,951 deaths associated with COVID-19 have been reported in Nepal. To prevent the spread of the virus, the GoN initiated various preventive and control measures, including lockdown strategies. The effects of COVID-19 are expected to persist for many years; the best strategies a resource-limited country such as Nepal can implement to control pandemic diseases such as COVID-19 in the pre-vaccine stage are to increase testing, tracing, and isolation capacity.

Why Climate Action Is Global Health Action.

The impacts of climate change on global health and populations are far-reaching, yet they disproportionately affect vulnerable groups, thereby exacerbating disparities. As humanity reckons with the emergency of climate change, our global health community needs to contend with our own contributions to greenhouse gas emissions. We know that transformation is possible and that climate action is the antidote to the existential challenge. As a global health community, we have an immense opportunity, responsibility, and commitment to lead, support, inspire, and empower climate action, research, and innovation that align deeply with our mission and core values.

Correction: Predictive markers for the early prognosis of dengue severity: A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pntd.0009808.].

Awareness and preparedness of healthcare workers against the first wave of the COVID-19 pandemic: A cross-sectional survey across 57 countries.

BACKGROUND: Since the COVID-19 pandemic began, there have been concerns related to the preparedness of healthcare workers (HCWs). This study aimed to describe the level of awareness and preparedness of hospital HCWs at the time of the first wave. METHODS: This multinational, multicenter, cross-sectional survey was conducted among hospital HCWs from February to May 2020. We used a hierarchical logistic regression multivariate analysis to adjust the influence of variables based on awareness and preparedness. We then used association rule mining to identify relationships between HCW confidence in handling suspected COVID-19 patients and prior COVID-19 case-management training. RESULTS: We surveyed 24,653 HCWs from 371 hospitals across 57 countries and received 17,302 responses from 70.2% HCWs overall. The median COVID-19 preparedness score was 11.0 (interquartile range [IQR] = 6.0-14.0) and the median awareness score was 29.6 (IQR = 26.6-32.6). HCWs at COVID-19 designated facilities with previous outbreak experience, or HCWs who were trained for dealing with the SARS-CoV-2 outbreak, had significantly higher levels of preparedness and awareness (p<0.001). Association rule mining suggests that nurses and doctors who had a 'great-extent-of-confidence' in handling suspected COVID-19 patients had participated in COVID-19 training courses. Male participants (mean difference = 0.34; 95% CI = 0.22, 0.46; p<0.001) and nurses (mean difference = 0.67; 95% CI = 0.53, 0.81; p<0.001) had higher preparedness scores compared to women participants and doctors. INTERPRETATION: There was an unsurprising high level of awareness and preparedness among HCWs who participated in COVID-19 training courses. However, disparity existed along the lines of gender and type of HCW. It is unknown whether the difference in COVID-19 preparedness that we detected early in the pandemic may have translated into disproportionate SARS-CoV-2 burden of disease by gender or HCW type.

Predictive markers for the early prognosis of dengue severity: A systematic review and meta-analysis.

BACKGROUND: Predictive markers represent a solution for the proactive management of severe dengue. Despite the low mortality rate resulting from severe cases, dengue requires constant examination and round-the-clock nursing care due to the unpredictable progression of complications, posing a burden on clinical triage and material resources. Accordingly, identifying markers that allow for predicting disease prognosis from the initial diagnosis is needed. Given the improved pathogenesis understanding, myriad candidates have been proposed to be associated with severe dengue progression. Thus, we aim to review the relationship between the available biomarkers and severe dengue. METHODOLOGY: We performed a systematic review and meta-analysis to compare the differences in host data collected within 72 hours of fever onset amongst the different disease severity levels. We searched nine bibliographic databases without restrictive criteria of language and publication date. We assessed risk of bias and graded robustness of evidence using NHLBI quality assessments and GRADE, respectively. This study protocol is registered in PROSPERO (CRD42018104495). PRINCIPAL FINDINGS: Of 4000 records found, 40 studies for qualitative synthesis, 19 for meta-analysis. We identified 108 host and viral markers collected within 72 hours of fever onset from 6160 laboratory-confirmed dengue cases, including hematopoietic parameters, biochemical substances, clinical symptoms, immune mediators, viral particles, and host genes. Overall, inconsistent case classifications explained substantial heterogeneity, and meta-analyses lacked statistical power. Still, moderate-certainty evidence indicated significantly lower platelet counts (SMD -0.65, 95% CI -0.97 to -0.32) and higher AST levels (SMD 0.87, 95% CI 0.36 to 1.38) in severe cases when compared to non-severe dengue during this time window. CONCLUSION: The findings suggest that alterations of platelet count and AST level-in the first 72 hours of fever onset-are independent markers predicting the development of severe dengue.

Emergence of cutaneous leishmaniasis in Nepal.

BACKGROUND: Cutaneous leishmaniasis (CL) is endemic in 70 countries worldwide. Nepal is considered non-endemic for CL and hence the control program is targeted to visceral leishmaniasis (VL) only. Here, we report the emergence of CL cases in different parts of Nepal. METHODS: We analyzed the CL and VL cases reported to Epidemiology and Diseases Control Division (EDCD), Ministry of Health and Population, Nepal through District Health Information System 2 (DHIS-2) and Early Warning and Reporting System (EWRS) during the past 4 years (2016-2019). Any laboratory-confirmed case was included in the study. Demographic and clinical details of each patient were transcribed into Excel sheets, verified with the case report forms and analyzed. RESULTS: VL has been reported in Nepal since 1980, but CL was reported very recently. From 2016 to 2019, 42 CL cases were reported from 26 different hospitals to EDCD which had been diagnosed on the basis of clinical presentation, and laboratory findings (demonstration of amastigotes in Giemsa-stained smears and rK39 test results). Majority of the patients (31.0%, 13/42) visited to the hospital within 1-6 months of onset of lesions. Facial region (38.1%, 16/42) was the common place where lesions were found ompared to other exposed parts of the body. CL was successfully treated with miltefosine for 28 days. The majority of CL patients did not have history of travel outside the endemic areas and there was no report of sandfly from these areas. CONCLUSION: These evidences highlight that the Government of Nepal need to pay more efforts on CL and include it in differential diagnosis by clinicians, and plan for an active surveillance when the country is targeting leishmaniasis elimination by the year 2025 with the decreasing number of VL cases.

Efficacy of face masks against respiratory infectious diseases: a systematic review and network analysis of randomized-controlled trials.

During the ongoing COVID-19 pandemic, face masks are among the most common and practical control measures used globally in reducing the risk of infection and disease transmission. Although several studies have investigated the efficacy of various face masks and respirators in preventing infection, the results have been inconsistent. Therefore, we performed a systematic review and network meta-analysis (NMA) of the randomized-controlled trials (RCTs) to assess the actual efficacy of face masks in preventing respiratory infections. We searched nine electronic databases up to July 2020 to find potential articles. We accepted trials reporting the protective efficacy of face masks against respiratory infections, of which the primary endpoint was the presence of respiratory infections. We used the ROB-2 Cochrane tool to grade the trial quality. We initially registered the protocol for this study in PROSPERO (CRD42020178516). Sixteen RCTs involving 17 048 individuals were included for NMA. Overall, evidence was weak, lacking statistical power due to the small number of participants, and there was substantial inconsistency in our findings. In comparison to those without face masks, participants with fit-tested N95 respirators were likely to have lesser infection risk (RR 0.67, 95% CI 0.38-1.19,P-score 0.80), followed by those with non-fit-tested N95 and non-fit-tested FFP2 respirators that shared the similar risk, (RR 0.73, 95% CI 0.12-4.36,P-score 0.63) and (RR 0.80, 95% CI 0.38-1.71,P-score 0.63), respectively. Next, participants who donned face masks with and without hand hygiene practices showed modest risk improvement alike (RR 0.89, 95% CI 0.67-1.17,P-score 0.55) and (RR 0.92, 95% CI 0.70-1.22,P-score 0.51). Otherwise, participants donning double-layered cloth masks were prone to infection (RR 4.80, 95% CI 1.42-16.27,P-score 0.01). Eleven out of 16 RCTs that underwent a pairwise meta-analysis revealed a substantially lower infection risk in those donning medical face masks (MFMs) than those without face masks (RR 0.83 95% CI 0.71-0.96). Given the body of evidence through a systematic review and meta-analyses, our findings supported the protective benefits of MFMs in reducing respiratory transmissions, and the universal mask-wearing should be applied-especially during the COVID-19 pandemic. More clinical data is required to conclude the efficiency of cloth masks; in the short term, users should not use cloth face masks in the outbreak hot spots and places where social distancing is impossible.

An Outbreak of Dengue Virus Serotype 2 Cosmopolitan Genotype in Nepal, 2017.

Dengue virus (DENV) is one of the most prevalent neglected tropical diseases, with half of the world's population at risk of infection. In Nepal, DENV was first reported in 2004, and its prevalence is increasing every year. The present study aimed to obtain and characterize the full-length genome sequence of DENV from the 2017 outbreak. Hospital-based surveillance was conducted in two provinces of Nepal during the outbreak. Acute-phase serum samples were collected from 141 clinically suspected dengue patients after the rainy season. By serological and molecular techniques, 37 (26.9%) and 49 (34.8%), respectively, were confirmed as dengue patients. The cosmopolitan genotype of DENV-2 was isolated from 27 laboratory-confirmed dengue patients. Genomic analysis showed many amino acid substitutions distributed mainly among the E, NS3, and NS5 genes. Phylogenetic analyses of the whole genome sequence revealed two clades (Asian and Indian) among DENV-2 isolates from Nepal. The DENV isolates from hilly and Terai areas were similar to Asian and Indian strains, respectively. Further genomic study on different DENV serotypes is warranted to understand DENV epidemics in Nepal, where there are limited scientific resources and infrastructure.