Typhoid is a public health problem in Nepal. To generate evidence on the impact of Typhoid Conjugate Vaccine (TCV), a phase 3, double-blind, randomized controlled trial was conducted in Lalitpur, ...Nepal. 20,000 children aged between 9 months and ≤16 years were vaccinated with a new TCV, or control vaccine. Participants were actively followed for safety and efficacy over 2 years through passive surveillance (PS) clinics. Several challenges were encountered during vaccination and PS stemming from misinformation, misconception, and fear around clinical trials in the community. Public engagement (PE) activities were conducted across various tiers moving from decision makers in the first tier; to elected local representatives in the second tier; ending with interaction in community with parents/guardians of the targeted population. Prior and during vaccination, engagement was conducted to inform about the study and discuss the importance of vaccination. Post-vaccination, engagement was conducted to inform about PS clinics, alleviate study concerns and share study updates. Direct and continuous interaction with community stakeholders, including parents/guardians of the targeted population contributed to build trust around the study and community willingness to be involved. It helped to raise awareness, drive away misconceptions, and allowed adaptation according to feedback from community members.
Objectives. Diabetic nephropathy is one of the major complications that develop over time in type 2 diabetes mellitus (T2DM). This prospective study was conducted to assess the diagnostic accuracy of ...serum cystatin C in detecting diabetic nephropathy at earlier stages. Materials and Methods. This study was undertaken on 50 cases of T2DM and 50 healthy subjects as controls. Demographic and anthropometric data and blood and urine samples were collected. The concentration of serum cystatin C (index test) and traditional markers of diabetic nephropathy, serum creatinine, and urinary microalbumin (the reference standard) were estimated. Similarly, blood glucose, glycated haemoglobin (HbA1c), triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, and urinary creatine were measured. Results. The mean ± SD serum cystatin C was significantly higher in T2DM as compared to control (1.07 ± 0.38 and 0.86 ± 0.12 mg/dl, respectively, p<0.001). The mean ± SD bodyweight, BMI, W : H ratio, pulse, SBP, and DBP were 66.4 ± 12.6 kg, 26.2 ± 5.6 kg/m2, 1.03 ± 0.09, 78 ± 7, 125 ± 16 mm of Hg, and 77 ± 9 mm of Hg, respectively, in cases. A significant difference in HDL cholesterol p=0.018 and serum cystatin C p<0.001 was observed among different grades of nephropathy. Cystatin C had a significant positive correlation with age (r = 0.323, p=0.022), duration of T2DM (r = 0.326, p=0.021), and UACR (r = 0.528, p<0.001) and a significant negative correlation with eGFR CKD-EPI cystatin C (r = −0.925, p<0.001). The area under ROC curve for serum cystatin C (0.611, 95% CI: 0.450–0.772) was greater than for serum creatinine (0.429, 95% CI: 0.265–0.593) though nonsignificant. Conclusion. Serum cystatin C concentration increases with the progression of nephropathy and duration of diabetes in Nepalese T2DM patients suggesting cystatin C as a potential marker of renal impairment in T2DM patients.
Invasive pneumococcal disease is one of the major causes of death in young children in resource poor countries. Nasopharyngeal carriage studies provide insight into the local prevalence of ...circulating pneumococcal serotypes. There are very few data on the concurrent carriage of multiple pneumococcal serotypes. This study aimed to identify the prevalence and serotype distribution of pneumococci carried in the nasopharynx of young healthy Nepalese children prior to the introduction of a pneumococcal conjugate vaccine using a microarray-based molecular serotyping method capable of detecting multi-serotype carriage. We conducted a cross-sectional study of healthy children aged 6 weeks to 24 months from the Kathmandu Valley, Nepal between May and October 2012. Nasopharyngeal swabs were frozen and subsequently plated on selective culture media. DNA extracts of plate sweeps of pneumococcal colonies from these cultures were analysed using a molecular serotyping microarray capable of detecting relative abundance of multiple pneumococcal serotypes. 600 children were enrolled into the study: 199 aged 6 weeks to <6 months, 202 aged 6 months to < 12 months, and 199 aged 12 month to 24 months. Typeable pneumococci were identified in 297/600 (49.5%) of samples with more than one serotype being found in 67/297 (20.2%) of these samples. The serotypes covered by the thirteen-valent pneumococcal conjugate vaccine were identified in 44.4% of samples containing typeable pneumococci. Application of a molecular serotyping approach to identification of multiple pneumococcal carriage demonstrates a substantial prevalence of co-colonisation. Continued surveillance utilising this approach following the introduction of routine use of pneumococcal conjugate vaccinates in infants will provide a more accurate understanding of vaccine efficacy against carriage and a better understanding of the dynamics of subsequent serotype and genotype replacement.
The COVID-19 pandemic has highlighted embedded inequities and fragmentation in our health systems. Traditionally, structural issues with health professional education perpetuate these. COVID-19 has ...highlighted inequities, but may also be a disruptor, allowing positive responses and system redesign. Examples from health professional schools in high and low- and middle-income countries illustrate pro-equity interventions of current relevance. We recommend that health professional schools and planners consider educational redesign to produce a health workforce well equipped to respond to pandemics and meet future need.
Aberrant iodine intake and thyroid autoimmunity affect thyroid function. Deficiencies of iodine including thyroid disorders have serious impact on child physical and mental development. This study ...was conducted to investigate iodine nutrition, thyroid function and thyroid autoimmunity in the Nepalese children, and explore the association of thyroidal autoimmunity with iodine nutrition and thyroid dysfunction.
Five schools from Udayapur district of eastern Nepal were selected for the study. A total of 213 school children aged 6-12 years were enrolled, and anthropometric data, urine samples and blood samples were collected. Urinary iodine concentration (UIC), free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and antithyroglobulin antibody (TgAb) was measured. Independent T test, Man-Whitney test, Chi-square test and Fisher's Exact test were used for testing statistical significance. Spearman's correlation analysis was done to find association between variables.
The median UIC with IQR, mean ± SD fT3, mean ± SD fT4, median TSH and TgAb with IQR was 150.0 μg/L (102.8; 204.0), 2.49 ± 0.83 pg/ml, 1.33 ± 0.42 ng/dl, 2.49 mIU/L (1.58; 4.29), and 21.40 IU/ml (15.54; 31.20) respectively. Elvated TgAb (≥30 IU/ml, thyroid autoimmune condition) was seen in 25.8% (
= 55) children. UIC was less than 100 μg/L in 17.4% (
= 37) of the children. Subclinical hypothyroidism, overt hypothyroidism and sublinical hyperthyroidism was seen in 1.4% (n = 3), 3.3% (
= 7) and 3.8% (
= 8) children respectively. A strong association of TgAb with UIC (r = - 0.210,
= 0.002) and thyroid hormones; fT3 (r = - 0.160,
= 0.019), fT4 (r = - 0.275,
< 0.001), and TSH (r = 0.296,
< 0.001) was seen. The relative risk for thyroid autoimmunity in children with UIC less than 100 μg/L was 1.784 (95% CI: 1.108-2.871,
= 0.024). Similarly, children with thyroid autoimmunity had higher relative risk 7.469 (95% CI: 2.790-19.995,
< 0.001) for thyroid dysfunction.
School children of eastern Nepal have adequate iodine nutrition. Thyroid autoimmunity is very common, while thyroid dysfunction is sparse in children. An association of thyroid autoimmunity with iodine nutrition and thyroid dysfunction was seen in children.
Summary Background Use of pneumococcal conjugate vaccines (PCVs) in resource-poor countries has focused on early infant immunisation with little emphasis on protection in late infancy and beyond. ...Boosting of the immune response later in infancy might provide improved persistence of immunogenicity into early childhood, however data are scarce. The aim of this study was to investigate if a two-dose prime with booster at age 9 months compared with a three-dose prime-only PCV schedule provided non-inferior immunogenicity in early infancy and superior persistence of antibody responses in early childhood. Methods We did an open-label, randomised, parallel group, controlled trial in healthy infants aged 40–60 days from Kathmandu, Nepal. Participants were randomly allocated (4:4:5 ratio) to receive PCV10 in addition to routine immunisations either as a two-dose prime and boost (2+1), three-dose prime (3+0), or two doses after completion of the initial study phase (0+2). We used a computer generated randomisation list with randomly varying block sizes. We followed up participants at age 2–4 years together with a group of unvaccinated controls. Sera were analysed for opsonophagocytic activity, protein D, and PCV10 serotype-specific IgG. Laboratory staff was masked to intervention group assignment. The primary outcome measure was to determine the proportion of participants in the 2+1 group at age 10 months with specific IgG for serotypes 1, 5, and 14 of at least 0·2 μg/mL in the per-protocol population. The secondary outcomes were non-inferiority (within 10% levels) at age 18 weeks for the proportion of participants in the 2+1 group compared with the 3+0 group with serotypes 1, 5, and 14 specific IgG of at least 0·2 μg/mL; the proportion of participants with PCV10 serotype-specific IgG of at least 0·2 μg/mL and opsonophagocytic activity reciprocal titre of at least 8 at ages 18 weeks and 10 months; and nasopharyngeal pneumococcal serotype-specific carriage rates at age 9 months in each study group. In the follow-up study, the primary outcome measure was the proportion of participants with IgG of at least 0·2 μg/mL for PCV10 serotypes at age 2–4 years in children previously immunised with a 3+0 schedule compared with a 2+1 schedule. The trial is registered with Current Controlled Trials, registration number ISRCTN56766232. Findings Between May 10, 2010, and Jan 7, 2011, 390 children were randomly assigned to each group: 119 to the 2+1 group, 120 to the 3+0 group, and 151 to the 0+2 group. At age 10 months, the proportions of 2+1 participants with IgG of at least 0·2 μg/mL were 99·0% (95% CI 94·2–100·0) for serotype 1, 100% (96·2–100·0) for serotype 5, and 97·9% (92·5–99·7) for serotype 14. At age 18 weeks, non-inferiority (within 10% levels) of the 2+1 group was shown compared with the 3+0 group, and there was no difference between the 2+1 and 3+0 groups for the proportion with IgG of at least 0·2 μg/mL for any of the PCV10 serotypes. At age 10 months, proportions with IgG of at least 0·2 μg/mL for serotypes 1, 5, 6B, and 23F, were higher in the 2+1 group than in the 3+0 group. At age 18 weeks, there were no differences in opsonophagocytic activity between the 2+1 and 3+0 groups for reciprocal titres of at least 8, but at age 10 months, proportions with an opsonophagocytic reciprocal titre of at least 8 for serotypes 1, 4, 5, 6B, 18C, 19F and 23F were higher in the 2+1 group than in the 3+0 group. At age 2–4 years, there were higher proportions in the 2+1 group versus the 3+0 group with IgG of at least 0·2 μg/mL for serotypes 1, 5, 6B, and 18C. Interpretation Use of a 2+1 PCV schedule with booster at age 9 months in a resource-poor setting improved antibody persistence through early childhood without compromising antibody responses in early infancy. This schedule is now recommended by WHO for progressive introduction across Nepal, with PCV10 introduction having commenced on Jan 18, 2015. Concurrent pre-implementation and post-implementation surveillance is being done by a GAVI Alliance funded study. Funding This study was supported by funding from the National Institute for Public Health and the Environment, The Netherlands; Oxford Vaccine Group, University of Oxford, UK; and GlaxoSmithKline Biologicals, Belgium.
In the era of growing antimicrobial resistance, there is a concern about the effectiveness of first-line antibiotics such as ampicillin in children hospitalized with community-acquired pneumonia. In ...this study, we describe antibiotic use and treatment outcomes among under-five children with community-acquired pneumonia admitted to a tertiary care public hospital in Nepal from 2017 to 2019. In this cross-sectional study involving secondary analysis of hospital data, there were 659 patients and 30% of them had a history of prehospital antibiotic use. Irrespective of prehospital antibiotic use, ampicillin monotherapy (70%) was the most common first-line treatment provided during hospitalization followed by ceftriaxone monotherapy (12%). The remaining children (18%) were treated with various other antibiotics alone or in combination as first-line treatment. Broad-spectrum antibiotics such as linezolid, vancomycin, and meropenem were used in less than 1% of patients. Overall, 66 (10%) children were required to switch to second-line treatment and only 7 (1%) children were required to switch to third-line treatment. Almost all (99%) children recovered without any sequelae. This study highlights the effectiveness of ampicillin monotherapy in the treatment of community-acquired pneumonia in hospitalized children in a non-intensive care unit setting.
New diagnostic tests for the etiology of childhood pneumonia are needed. We evaluated the antibody-in-lymphocyte supernatant (ALS) assay to detect immunoglobulin (Ig) G secretion from
peripheral ...blood mononuclear cell (PBMC) culture, as a potential diagnostic test for pneumococcal pneumonia. We enrolled 348 children with pneumonia admitted to Patan Hospital, Kathmandu, Nepal between December 2015 and September 2016. PBMCs sampled from participants were incubated for 48 h before harvesting of cell culture supernatant (ALS). We used a fluorescence-based multiplexed immunoassay to measure the concentration of IgG in ALS against five conserved pneumococcal protein antigens. Of children with pneumonia, 68 had a confirmed etiological diagnosis: 12 children had pneumococcal pneumonia (defined as blood or pleural fluid culture-confirmed; or plasma CRP concentration ≥60 mg/l and nasopharyngeal carriage of serotype 1 pneumococci), and 56 children had non-pneumococcal pneumonia. Children with non-pneumococcal pneumonia had either a bacterial pathogen isolated from blood (six children); or C-reactive protein <60 mg/l, absence of radiographic consolidation and detection of a pathogenic virus by multiplex PCR (respiratory syncytial virus, influenza viruses, or parainfluenza viruses; 23 children). Concentrations of ALS IgG to all five pneumococcal proteins were significantly higher in children with pneumococcal pneumonia than in children with non-pneumococcal pneumonia. The concentration of IgG in ALS to the best-performing antigen discriminated between children with pneumococcal and non-pneumococcal pneumonia with a sensitivity of 1.0 (95% CI 0.73-1.0), specificity of 0.66 (95% CI 0.52-0.78) and area under the receiver-operating characteristic curve (AUROCC) 0.85 (95% CI 0.75-0.94). Children with pneumococcal pneumonia were older than children with non-pneumococcal pneumonia (median 5.6 and 2.0 years, respectively,
< 0.001). When the analysis was limited to children ≥2 years of age, assay of IgG ALS to pneumococcal proteins was unable to discriminate between children with pneumococcal pneumonia and non-pneumococcal pneumonia (AUROCC 0.67, 95% CI 0.47-0.88). This method detected spontaneous secretion of IgG to pneumococcal protein antigens from cultured PBMCs. However, when stratified by age group, assay of IgG in ALS to pneumococcal proteins showed limited utility as a test to discriminate between pneumococcal and non-pneumococcal pneumonia in children.
Oxidative stress and malnutrition are shown to have pathogenic effect in Chronic Obstructive Pulmonary Disease (COPD).
This study was done to assess the burden of oxidative stress in COPD and to ...determine its relation to their nutritional status.
In this cross-sectional study, 100 COPD cases from emergency and medical ward and meeting inclusion criteria, along with age, sex and occupation (mainly farmers, housewives and drivers) matched 100 controls without COPD and meeting inclusion criteria were enrolled. Oxidative stress was assessed by measuring lipid peroxidation product, Malondialdehyde (MDA) and antioxidants, like Vitamin C, E and Red Blood Cell Catalase (RBCC). Mini Nutritional Assessment (MNA) tool and Body Mass Index (BMI) were used to assess nutritional status.
Chi-square test was applied for categorical variable. Student t-test was applied for comparison of means. Analysis of Variance (ANOVA) was applied for comparison between groups followed by Bonferroni post hoc analysis. Pearson correlation method was used for quantitative variables. Statistical significance was defined as p< 0.05 (two tailed).
COPD cases had significantly high MDA level with low level of Vitamin E and catalase as compared to controls (p < 0.001). Most of the COPD cases were underweight (BMI ≤ 18.5 Kg/m(2)) and malnourished (MNA score less than 7). Bonferroni post-hoc analysis, showed significantly high burden of oxidative stress in underweight and malnourished cases as compared to normal weight (p < 0.05) among COPD cases. Highly significant correlation was seen between BMI and plasma MDA level (r = -0.27, p = 0.008) in COPD cases.
This study shows impaired oxidant/antioxidant balance along with malnutrition and underweight in COPD, which signals for considering antioxidant therapy along with nutritional management.
Nepal is a low-income, landlocked country located on the Indian subcontinent between China and India. The challenge of finding human resources for rural community health care settings is not unique ...to Nepal. In spite of the challenges, the health sector has made significant improvement in national health indices over the past half century. However, in terms of access to and quality of health services and impact, there remains a gross urban-rural disparity. The Patan Academy of Health Sciences (PAHS) has adopted a community-based education model, termed "community based learning and education" (CBLE), as one of the principal strategies and pedagogic methods. This method is linked to the PAHS mission of improving rural health in Nepal by training medical students through real-life experience in rural areas and developing a positive attitude among its graduates towards working in rural areas. This article outlines the PAHS approach of ruralizing the academy, which aligns with the concept of community engagement in health professional education. We describe how PAHS has embedded medical education in rural community settings, encouraging the learning context to be rural, fostering opportunities for community and peripheral health workers to participate in teaching-learning as well as evaluation of medical students, and involving community people in curriculum design and implementation.
PDF
