Climate change and childhood diarrhoea in Kathmandu, Nepal: a health risk assessment and exploration of surveillance capacity

There is substantial evidence that the onset and transmission of infectious diseases, particularly vector-borne diseases and diarrheal diseases, are influenced by many factors including climate change. Improving the understanding of the impacts of climate change on infectious diseases is important to inform policy decision making on disease control and prevention, as well as predicting the trends in the infectious diseases burden. Epidemiological analysis of long-term surveillance data on infectious diseases and meteorological factors are instrumental in establishing the association between infectious disease incidence and climate change. Advanced epidemiological techniques are now available to precisely estimate the nature of association (linear, non-linear) as well as the delayed effect: this means that it is possible to plan and design climate-based early warning systems to predict conditions that are likely to be favourable for an outbreak of climate-sensitive infectious disease. However, the association between infectious diseases and climate change varies, depending upon the pathogens responsible for infection. Similarly, the ability of infectious disease surveillance systems or disease control divisions to generate this evidence and utilise the knowledge to cope or adapt to the impacts of climate change is contingent upon the social, economic, political and other contextual problems. In the Nepalese context, the impacts of climate change on infectious diseases, in particular diarrheal disease, remains unknown: similarly, there has been no exploration of the contextual factors associated with the integration of climate change-related risk in Nepalese infectious diseases surveillance systems. Given this background, the first aim of this PhD thesis is to characterize the association between diarrhoea among children below five years of age and climate variables in Kathmandu, Nepal and then project the future burden of diarrhoea due to climate change. The second aim is to understand the association between rotavirus infection among children below five years of age and temperature variability in Kathmandu and compute the fraction of rotavirus infection that is attributable to temperature. The third aim is to explore the extant research on climate change and infectious diseases in Nepal and to identify the reasons behind sparse evidence on the topic. The final aim is to explore social, economic and cultural factors associated with infectious diseases surveillance in Nepal in the context of climate change. A mixed method study design was employed to achieve the goals of this project. There are four analytical chapters in this thesis: two quantitative studies; a study that reviews evidence of the impacts of climate change on infectious disease and policy documents related to infectious disease control and prevention in Nepal; and a qualitative study. Two quantitative studies were carried out to estimate the association between climate variability and childhood diarrhoea, and childhood rotavirus infection in Kathmandu. Study 1 and study 2 utilised time series design involving Poisson regression equations fitted with distributed lag models to characterise exposure-response and possible lagged association between climate variables and diarrhoea, and rotavirus infection. A qualitative research study was undertaken to explore the social, economic, cultural and political factors associated with infectious diseases surveillance in the context of climate change in Nepal. In study 4, semi-structured interviews were conducted with key informants and stakeholders from the Department of Health Services Nepal, World Health Organization Nepal, the Department of Hydrology and Meteorology Nepal and infectious disease experts working in both public and private sectors in Nepal. The interviews and subsequent thematic analysis of data were conducted from a critical realist perspective. Study 1 established a significant positive association between childhood diarrhoea and temperature, and rainfall. A 1°C increase in maximum temperature above the monthly average was found to be associated with 8.1% (RR: 1.081; 95% CI: 1.02-1.14) increase in the monthly count of diarrhoea among children below five years of age living in Kathmandu, Nepal. Similarly, a 10mm increase in monthly cumulative rainfall above the mean value was associated with 0.09% (RR: 1.009; 95% CI: 1.004-1.015) increase in childhood diarrhoea. It was further projected that 1357 (UI: 410–2274) additional cases of childhood diarrhoea could be experienced by 2050 given the projected change in climate under low-risk scenario (0.9°C increase in maximum temperature). Study 2 established a nonlinear negative association between temperature (maximum, mean and minimum) and weekly rotavirus infection cases among children below five years of age in Kathmandu. Compared to the median value of mean temperature, an increased risk (RR: 1.52; 95% CI: 1.08–2.15) of rotavirus infection was detected at the lower quantile (10th percentile) and a decreased risk (RR: 0.64; 95% CI: 0.43–0.95) was detected at the higher quantile (75th percentile). Similarly, an increased risk [(RR: 1.93; 95% CI: 1.40–2.65) and (RR: 1.42; 95% CI: 1.04–1.95)] of infection was detected for both maximum and minimum temperature at their lower quantile (10th percentile). It was further estimated that 47.01% of the rotavirus infection cases reported between 2013 and 2016 in Kathmandu could be attributed to minimum temperature. Study 3 identified that there was little evidence describing the impacts of climate change on infectious diseases and no evidence describing the projected burden under climate change scenarios. I explored the reasons behind paucity in the evidence and challenges faced by epidemiologists in Nepal. The challenges identified included poor quality infectious disease datasets, shortage of trained human resources, inadequate funding and political instability. As such, it was recommended that an integrated digital network of interdisciplinary experts be established and increased collaboration among different stakeholders be promoted to advance the evidence base on the impacts of climate change on infectious diseases in Nepal. The fourth and final study outlined that climate change and its impacts on infectious disease surveillance is treated as a less serious issue than other more ‘salient’ public health risks in the context of Nepal. The study further illustrates how climate change is variably constructed as a contingent risk for infectious diseases transmission and public health systems. The analysis exposes a weaker alliance among different stakeholders, particularly policymakers and evidence generators that leads to the continuation of traditional practices of infectious diseases surveillance without consideration of the impacts of climate change. In summary, this thesis brings to prominence important progress in understanding the link between climate change and infectious diseases, in particular childhood diarrhoea, in a subtropical highland climate from a low and middle income South Asian country. So far, we have not found any other study that explores the contextual factors (social, economic, cultural and political) that impede the integration of climate change-related risk in the disease surveillance systems. Therefore, this thesis illustrates a novel facet of infectious disease surveillance and climate change. This thesis makes an important contribution to address the gap on information related to climate change and infectious diseases in Nepal and can have significant implications towards building a climate-resilient public health system in Nepal.Thesis (Ph.D.) -- University of Adelaide, School of Public Health, 202

Late presentation of congenital diaphragmatic hernia: A diagnostic dilemma

Congenital diaphragmatic hernias are commonly symptomatic within 24 hours after birth, but late presentation is not uncommon. Late presentation of congenital diaphragmatic hernia poses diagnostic difficulties as clinical picture are vague, and more commonly presented with non-specific gastrointestinal and respiratory symptoms. Due to the vague and non-specific clinical presentation, clinician faces a diagnostic dilemma resulting in delay in diagnosis and many a times an inappropriate management. This article reports 2 cases of late-presenting congenital diaphragmatic hernia (over the period of 6 months from September 2014 to February 2015) in National Institute of Disease of Chest and Hospital (NIDCH). In first case, she was diagnosed as right-sided tubercular pleural effusion and was treated with CAT-1 anti-tubercular therapy for 6 months without any clinical improvement. Later CT scan of chest was done and diagnosed as a case of congenital diaphragmatic hernia. The second case was diagnosed as a left-sided hydropneumothorax and treated with left tube thoracostomy. During removal of the intercostal chest tube, some fatty tissue was pulled out of the thoracostomy site. In NIDCH, she was diagnosed as a case of diaphragmatic hernia by barium follow-through. Both cases were diagnosed as Bochdalek hernia during the repair of the hernia defect via thoracotomy

Detection of Pyuria by Microscopic Urinalysis as a Marker of Pediatric Urinary Tract Infection

Globally, different diagnostic tests of urinary tract infection (UTI) are in clinical practices. A reliable test can increase the efficiency of the healthcare system, especially in a developing country like Nepal, reducing cost and time. Thus, we accessed the possibility of pyuria detected by microscopic urinalysis as a marker of pediatric UTI. The prospective study was conducted fromJuly2014 to January 2015 at Alka hospital, Lalitpur. Microscopic urinalysis of 353clean-catch urine samples was done by the wet mount method, followed by urine culture by a semi-quantitative method. We confirmed 64 (18.1%) UTI cases by culture, the gold standard for UTI diagnosis. Fever was the most common clinical manifestation in UTI cases. The sensitivity, specificity, positive predictive value and negative predictive value of pyuria detected by microscopic urinalysis to identify UTI were 50%, 70.9%, 27.6% and 86.5% respectively. In 318 febrile cases, the sensitivity, specificity, positive predictive value and negative predictive value of pyuria detected by microscopic urinalysis to identify UTI were 73.2%, 72.6%, 28.3% and 94.8% respectively. The findings suggest pyuria detected by microscopic urinalysis as not a worth while marker of pediatric UTI. But it is a trust worthy marker in febrile pediatric cases

Real Time Spectroscopic Ellipsometry Analysis of First Stage CuIn1-xGaxSe2 Growth: Indium-Gallium Selenide Co-Evaporation

Real time spectroscopic ellipsometry (RTSE) has been applied for in-situ monitoring of the first stage of copper indium-gallium diselenide (CIGS) thin film deposition by the three-stage co-evaporation process used for fabrication of high efficiency thin film photovoltaic (PV) devices. The first stage entails the growth of indium-gallium selenide (In1-xGax)₂Se₃ (IGS) on a substrate of Mo-coated soda lime glass maintained at a temperature of 400 °C. This is a critical stage of CIGS deposition because a large fraction of the final film thickness is deposited, and as a result precise compositional control is desired in order to achieve the optimum performance of the resulting CIGS solar cell. RTSE is sensitive to monolayer level film growth processes and can provide accurate measurements of bulk and surface roughness layer thicknesses. These in turn enable accurate measurements of the bulk layer optical response in the form of the complex dielectric function ε = ε₁ - iε₂, spectra. Here, RTSE has been used to obtain the (ε₁, ε₂) spectra at the measurement temperature of 400 °C for IGS thin films of different Ga contents (x) deduced from different ranges of accumulated bulk layer thickness during the deposition process. Applying an analytical expression in common for each of the (ε₁, ε₂) spectra of these IGS films, oscillator parameters have been obtained in the best fits and these parameters in turn have been fitted with polynomials in x. From the resulting database of polynomial coefficients, the (ε₁, ε₂) spectra can be generated for any composition of IGS from the single parameter, x. The results have served as an RTSE fingerprint for IGS composition and have provided further structural information beyond simply thicknesses, for example information related to film density and grain size. The deduced IGS structural evolution and the (ε₁, ε₂) spectra have been interpreted as well in relation to observations from scanning electron microscopy, X-ray diffractometry and energy-dispersive X-ray spectroscopy profiling analyses. Overall the structural, optical and compositional analysis possible by RTSE has assisted in understanding the growth and properties of three stage CIGS absorbers for solar cells and shows future promise for enhancing cell performance through monitoring and control

Health System Capacity and Access Barriers to Diagnosis and Treatment of CVD and Diabetes in Nepal

Background: Universal access to essential medicines and routine diagnostics is required to combat the growing burden of cardiovascular disease (CVD) and diabetes. Evaluating health systems and various access dimensions – availability, affordability, accessibility, acceptability, and quality – is crucial yet rarely performed, especially in low- and middle-income countries. Objective: To evaluate health system capacity and barriers in accessing diagnostics and essential medicines for CVD and diabetes in Nepal. Methods: We conducted a WHO/HAI nationally-representative survey in 45 health-facilities (public sector: 11; private sector: 34) in Nepal to collect availability and price data for 21 essential medicines for treating CVD and diabetes, during May–July 2017. Data for 13 routine diagnostics were obtained in 12 health facilities. Medicines were considered unaffordable if the lowest paid worker spends >1 day’s wage to purchase a monthly supply. To evaluate accessibility, we conducted facility exit interviews among 636 CVD patients. Accessibility (e.g., private-public health facility mix, travel to hospital/pharmacy) and acceptability (i.e. Nepal’s adoption of WHO Essential Medicine List, and patient medication adherence) were summarized using descriptive statistics, and we conducted a systematic review of relevant literature. We did not evaluate medicine quality. Results: We found that mean availability of generic medicines is low (<50%) in both public and private sectors, and less than one-third medicines met WHO’s availability target (80%). Mean (SD) availability of diagnostics was 73.1% (26.8%). Essential medicines appear locally unaffordable. On average, the lowest-paid worker would spend 1.03 (public sector) and 1.26 (private sector) days’ wages to purchase a monthly medicine supply. For a person undergoing CVD secondary-prevention interventions in the private sector, the associated expenditure would be 7.5–11.2% of monthly household income. Exit interviews suggest that a long/expensive commute to health facilities and poor medicine affordability constrain access. Conclusions: This study highlights critical gaps in Nepal’s health system capacity to offer basic health services to CVD and diabetes patients, owing to low availability and poor affordability and accessibility. Research and policy initiatives are needed to ensure uninterrupted supply of affordable essential medicines and diagnostics

The expression of mismatched repair genes and their correlation with clinicopathological parameters and response to neo-adjuvant chemotherapy in breast cancer

BACKGROUND: The DNA mismatch repair (MMR) pathway is an important post-replicative repair process. It is involved in the maintenance of genomic stability and MMR genes have therefore been named the proofreaders of replicating DNA. These genes repair the replicative errors of DNA and are thus imperative for genomic stability. The MMR genes have been found to be involved in promoting cytotoxicity, apoptosis, p53 phosphorylation and cell cycle arrest following exposure to exogenous DNA damaging agents. Loss of MMR function prevents the correction of replicative errors leading to instability of the genome, and can be detected by polymorphisms in micro satellites (1–6 nucleotide repeat sequences scattered in whole of the genome). This phenomenon, known as micro satellite instability (MSI), is a hallmark of MMR dysfunction and can be used as a marker of MMR dysfunction in colorectal and other malignancies. An alternative method for detection of MMR dysfunction is to test the expression of protein products of the MMR genes by immunohistochemistry (IHC), as mutations in these genes lead to reduced or absent expression of their gene products. Correlation between loss of MMR function and clinical, histopathological, behavioral parameters of the tumor and its response to chemotherapy in breast cancers may be of value in predicting tumor behavior and response to neoadjuvant chemotherapy (NACT). Neoadjuvant chemotherapy is an integral part of multimodal therapy for locally advanced breast cancer and predicting response may help in tailoring regimens in patients for optimum response. MATERIALS: After approval by the IRB(Institutional Review Board) and ethical committee of the hospital, 31 cases of locally advanced breast carcinoma (LABC) were studied to assess the correlation between MMR dysfunction, clinicopathological parameters and objective clinical response to neoadjuvant chemotherapy using immunohistochemistry. The immunohistochemical analysis for four MMR protein products -MLH1, MSH2, MSH6 and PMS2 was done in the pre NACT trucut biopsy specimen and after three cycles of NACT with C AF (cyclophosphamide, adriamycin, 5-fluorouracil) regimen, in the modified radical mastectomy specimen. RESULTS AND CONCLUSION: There was no significant correlation observed between expression of MMR proteins and age, family history, tumor size or histological type. However there was a statistically significant negative correlation between MLH1, MSH2 expression and histological grade. There was also a negative correlation observed between PMS2 expression after neo-adjuvant chemotherapy and clinical response. Cases with high post NACT expression of PMS2 were poor responders to chemotherapy. MSH6 was the most frequently altered MMR gene, with a negativity rate of 48% and the patients with high expression responded poorly to NACT. The study highlights the possible role of MMR expression in predicting aggressive tumor behavior (histological grade) and response to neoadjuvant chemotherapy in patients with LABC

The COVID‐19 Pandemic Not Only Poses Challenges, but Also Opens Opportunities for Sustainable Transformation

The COVID-19 pandemic has impacted social, economic, and environmental systems worldwide, slowing down and reversing the progress made in achieving the Sustainable Development Goals (SDGs). SDGs belong to the 2030 Agenda to transform our world by tackling humankind's challenges to ensure well-being, economic prosperity, and environmental protection. We explore the potential impacts of the pandemic on SDGs for Nepal. We followed a knowledge co-creation process with experts from various professional backgrounds, involving five steps: online survey, online workshop, assessment of expert's opinions, review and validation, and revision and synthesis. The pandemic has negatively impacted most SDGs in the short term. Particularly, the targets of SDG 1, 4, 5, 8, 9, 10, 11, and 13 have and will continue to have weakly to moderately restricting impacts. However, a few targets of SDG 2, 3, 6, and 11 could also have weakly promoting impacts. The negative impacts have resulted from impeding factors linked to the pandemic. Many of the negative impacts may subside in the medium and long terms. The key five impeding factors are lockdowns, underemployment and unemployment, closure of institutions and facilities, diluted focus and funds for non-COVID-19-related issues, and anticipated reduction in support from development partners. The pandemic has also opened a window of opportunity for sustainable transformation, which is short-lived and narrow. These opportunities are lessons learned for planning and action, socio-economic recovery plan, use of information and communication technologies and the digital economy, reverse migration and “brain gain,” and local governments' exercising authorities

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019 : a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dosespecific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in countryreported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings By 2019, global coverage of third-dose DTP (DTP3; 81.6% [95% uncertainty interval 80.4-82 .7]) more than doubled from levels estimated in 1980 (39.9% [37.5-42.1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38.5% [35.4-41.3] in 1980 to 83.6% [82.3-84.8] in 2019). Third- dose polio vaccine (Pol3) coverage also increased, from 42.6% (41.4-44.1) in 1980 to 79.8% (78.4-81.1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56.8 million (52.6-60. 9) to 14.5 million (13.4-15.9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe