Country ownership as a guiding principle for IA2030: A case study of the measles and rubella elimination programs in Nepal and Nigeria.

Country-owned, as opposed to donor-driven, is a principle within the development sector that recognizes the centrality of countries' leadership, systems, and resources in executing programs and achieving sustainable development. In alignment with this notion, the Immunization Agenda 2030 was developed with country ownership as one of four core principles of the ambitious ten-year plan. This means that the success of immunization programs, including those with eradication and elimination goals such as polio, measles, and rubella, and those with broader equity goals to "leave no one behind" on immunization, would be largely driven by country systems. In this paper we deconstruct country ownership into five operational principles: commitment, coordination, capacity, community participation, and accountability. Through this lens, we illustrate how two countries, Nepal and Nigeria, have exemplified country ownership in their measles and rubella elimination programs and we infer the ways in which country ownership drives system performance and sustains program efforts.

Effect of the of 10-valent pneumococcal conjugate vaccine in Nepal 4 years after introduction: an observational cohort study.

BACKGROUND: In Nepal, Streptococcus pneumoniae (pneumococcus) is a common cause of bacterial pneumonia in children, and is a major health concern. There are few data on the effect of vaccination on the disease or colonisation with pneumococci in the nasopharynx of children in this setting. The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the routine infant immunisation schedule in Nepal in 2015. We aimed to investigate the effect of the introduction of PCV10 on pneumococcal carriage and disease in children in Nepal. METHODS: We did an observational cohort study in children in Nepal. The hospital surveillance study took place in Patan Hospital, Kathmandu, and community studies in healthy children took place in Kathmandu and Okhaldhunga district. For the surveillance study, all children admitted to Patan Hospital between March 20, 2014, and Dec 31, 2019, aged between 2 months and 14 years with clinician-suspected pneumonia, were eligible for enrolment. For the community study, healthy children aged 0-8 weeks, 6-23 months, and 24-59 months were recruited from Kathmandu, and healthy children aged 6-23 months were recruited from Okhaldhunga. We assessed the programmatic effect of PCV10 introduction using surveillance for nasopharyngeal colonisation, pneumonia, and invasive bacterial disease from 1·5 years before vaccine introduction and 4·5 years after vaccine introduction. For the surveillance study, nasopharyngeal swabs, blood cultures, and chest radiographs were obtained from children admitted to Patan Hospital with suspected pneumonia or invasive bacterial disease. For the community study, nasopharyngeal swabs were obtained from healthy children in the urban and rural settings. Pneumonia outcomes were analysed using log-binomial models and adjusted prevalence ratios (aPR) comparing each calendar year after the introduction of the vaccine into the national programme with the pre-vaccine period (2014-15), adjusted for calendar month, age, and sex. FINDINGS: Between March 20, 2014, and Dec 31, 2019, we enrolled 2051 children with suspected pneumonia, and 11 354 healthy children (8483 children aged 6-23 months, 761 aged 24-59 months, and 2110 aged 0-8 weeks) to assess nasopharyngeal colonisation. Among clinical pneumonia cases younger than 2 years, vaccine serotype carriage declined 82% (aPR 0·18 [95% CI 0·07-0·50]) by 2019. There was no decrease in vaccine serotype carriage in cases among older unvaccinated age groups. Carriage of the additional serotypes in PCV13 was 2·2 times higher by 2019 (aPR 2·17 [95% CI 1·16-4·05]), due to increases in serotypes 19A and 3. Vaccine serotype carriage in healthy children declined by 75% in those aged 6-23 months (aPR 0·25 [95% CI 0·19-0·33]) but not in those aged 24-59 months (aPR 0·59 [0·29-1·19]). A decrease in overall vaccine serotype carriage of 61% by 2019 (aPR 0·39 [95% CI 0·18-0·85]) was also observed in children younger than 8 weeks who were not yet immunised. Carriage of the additional PCV13 serotypes in children aged 6-23 months increased after PCV10 introduction for serotype 3 and 19A, but not for serotype 6A. The proportion of clinical pneumonia cases with endpoint consolidation on chest radiographs declined from 41% in the pre-vaccine period to 25% by 2018, but rose again in 2019 to 36%. INTERPRETATION: The introduction of the PCV10 vaccine into the routine immunisation programme in Nepal has reduced vaccine serotype carriage in both healthy children and children younger than 2 years with pneumonia. Increases in serotypes 19A and 3 highlight the importance of continued surveillance to monitor the effect of vaccine programmes. This analysis demonstrates a robust approach to assessing vaccine effect in situations in which pneumococcal disease endpoint effectiveness studies are not possible. FUNDING: Gavi, the Vaccine Alliance and the World Health Organization.

An ensemble deep learning classifier for sentiment analysis on code-mix Hindi-English data.

Code-mixing on social media is a trend in many countries where people speak multiple languages, such as India, where Hindi and English are major communication languages. Sentiment analysis is beneficial in understanding users' opinions and thoughts on social, economic, and political issues. It eliminates the manual monitoring of each and every review, which is a cumbersome task. However, performing sentiment analysis on code-mix data is challenging, as it involves various out of vocabulary terms and numerous issues, making it a new field in natural language processing. This work includes dealing with such text and ensembling a classifier to detect sentiment polarity. Our classifier ensembles a multilingual variant of RoBERTa and a sentence-level embedding from Universal Sentence Encoder to identify the sentiments of these code-mixed tweets with higher accuracy. This ensemble optimises the classifier's performance by using the strength of both for transfer learning. Experiments were conducted on real-life benchmark datasets and revealed their sentiment. The performance of the proposed classifier framework is compared with other baselines and deep learning models on five datasets to show the superiority of our results. Results showed improved and increased performance in the proposed classifier's accuracy, precision, and recall. The accuracy achieved by our classifier on code-mix datasets is 66% on Joshi et al. 2016, 60% on SAIL 2017, and 67% on SemEval 2020 Task-9 dataset, which is on average around 3% as compared to contemporary baselines.

Nepal measles outbreak response immunization during COVID-19: A risk-based intervention strategy.

In 2020, National Immunization Programme (NIP) of Nepal implemented a measles outbreak response immunization (ORI) campaign, which was additional to an ongoing preventive measles-rubella SIA campaign. Both campaigns were implemented during ongoing COVID-19 transmission. By April, 220 measles cases and two deaths were confirmed from eight districts of Nepal. The NIP triangulated information from surveillance (measles and COVID-19), measles immunization performance and immunity profile, programme capacities and community engagement and applied a logical decision-making framework to the collated data to inform 'Go/No-Go' decisions for ORI interventions. This was reviewed by the National Immunization Advisory Committee (NIAC) for endorsement. Outbreak response with non-selective immunization (ORI), vitamin-A administration and case management were implemented in affected municipalities of four districts, while in the remaining districts outbreak response without ORI were undertaken. The structure and iterative application of this logical framework has been described. ORI was implemented without interrupting the ongoing measles-rubella vaccination campaign which had targeted children from 9 to 59 months of age. The age group for ORI was same as SIA in one sub-district area, while for the other three sub-district areas it was from 6 months to 15 years of age. More than 32,000 persons (97% coverage) were vaccinated in ORI response. Overall measles incidence decreased by 98% after ORI. The daily incidence rate of measles was 94 times higher (95% confidence interval: 36.11 - 347.62) before the ORI compared to two weeks after ORI until year end. Close attention to surveillance and other data to inform actions and seamless collaboration between NIP and core immunization partners (WHO, UNICEF), with guidance from NIAC were key elements in successful implementation. This was an example of feasible application of the global framework for implementation of a mass vaccination campaign during COVID-19 through application of a simple decision-making logical framework.

Childhood Invasive Bacterial Disease in Kathmandu, Nepal (2005-2013).

BACKGROUND: Invasive bacterial disease (IBD; including pneumonia, meningitis, sepsis) is a major cause of morbidity and mortality in children in low-income countries. METHODS: We analyzed data from a surveillance study of suspected community-acquired IBD in children <15 years of age in Kathmandu, Nepal, from 2005 to 2013 before introduction of pneumococcal conjugate vaccines (PCV). We detailed the serotype-specific distribution of invasive pneumococcal disease (IPD) and incorporated antigen and PCR testing of cerebrospinal fluid (CSF) from children with meningitis. RESULTS: Enhanced surveillance of IBD was undertaken during 2005-2006 and 2010-2013. During enhanced surveillance, a total of 7956 children were recruited of whom 7754 had blood or CSF culture results available for analysis, and 342 (4%) had a pathogen isolated. From 2007 to 2009, all 376 positive culture results were available, with 259 pathogens isolated (and 117 contaminants). Salmonella enterica serovar Typhi was the most prevalent pathogen isolated (167 cases, 28% of pathogens), followed by Streptococcus pneumoniae (98 cases, 16% pathogens). Approximately, 73% and 78% of pneumococcal serotypes were contained in 10-valent and 13-valent PCV, respectively. Most cases of invasive pneumococcal disease (IPD) were among children ≥5 years of age from 2008 onward. Antigen and PCR testing of CSF for pneumococci, Haemophilus influenzae type b and meningococci increased the number of these pathogens identified from 33 (culture) to 68 (culture/antigen/PCR testing). CONCLUSIONS: S. enterica serovar Typhi and S. pneumoniae accounted for 44% of pathogens isolated. Most pneumococcal isolates were of serotypes contained in PCVs. Antigen and PCR testing of CSF improves sensitivity for IBD pathogens.

Vaccine safety surveillance informs public health policy beyond immunization: A case-series on bleeding following vaccination, Nepal, 2016-2018.

BACKGROUND: Surveillance for adverse events following immunization (AEFI) is important to monitor vaccine safety and should lead to appropriate responses to improve health and immunization program. Bleeding following vaccination is not recognized as an important AEFI. Without policy of vitamin K (VK) prophylaxis at birth, vitamin K deficiency bleeding (VKDB) could be an important cause of bleeding in young infants and may manifest as AEFI. METHODS: We retrospectively analysed all serious AEFI cases that presented with external or internal bleeding reported to Nepal's AEFI surveillance system during 2016-2018. The cases were classified as VKDB, suspected VKDB or non-VKDB. RESULTS: During the period, 16 serious AEFI with symptom or sign of bleeding were reported representing 21.3% of all serious AEFI reported. Cases were between 40 and 94 days of age. The National AEFI Investigation Committee classified all cases as coincidental. Fourteen cases (87.5%) had bleeding from injection site. Median time from vaccination to injection site bleeding was 4.3 h (interquartile range: 2.1-11.6 h). Six cases (37.5%) had intra-cranial haemorrhage. Only one case had confirmed history of receiving VK at birth. Ten cases (62.5%) received appropriate treatment (VK injection; blood transfusion if needed). Based on limited laboratory investigations available, three cases (18.75%) could be classified as late onset VKDB and 11 cases (68.75%) as suspected late onset VKDB. CONCLUSION: VKDB should be suspected in young infants presenting with bleeding including following vaccination, and prompt treatment should be initiated. Bleeding following vaccination should be recognized as an important AEFI as even a small amount of blood loss in young infants can be catastrophic. We posit that this series is a small subset of VKDB cases in Nepal detected through AEFI surveillance system. In countries without policy of VK prophylaxis at birth including Nepal, the policy should be introduced.

Kinetic modeling as a tool to understand the influence of cell culture process parameters on the glycation of monoclonal antibody biotherapeutics.

Glycation, the nonenzymatic reaction between the reducing sugar glucose and the primary amine residues on amino acid side chains, commonly occurs in the cell culture supernatant during production of therapeutic monoclonal antibodies (mAbs). While glycation has the potential to impact efficacy and pharmacokinetic properties for mAbs, the most common undesirable impact of glycation is on the distribution of charged species, often a release specification for commercial processes. Existing empirical approaches are usually insufficient to rationalize the effects of cell line and process changes on glycation. To address this gap, we developed a kinetic model for estimating mAb glycation levels during the cell culture process. The rate constant for glycation, including temperature and pH dependence, was estimated by fitting the kinetic model to time-course glycation data from bioreactors operated at different process settings that yielded a wide range of glycation values. The parameter values were further validated by independently estimating glycation rate constants using cell-free incubation studies at various temperatures. The model was applied to another mAb, by re-estimating the activation energy to account for effect of a glycation "hotspot". The model was further utilized to study the role of temperature shift as an approach to reduce glycation levels in the manufacturing process for mAb2. While a downshift in temperature resulted in lowering of glycation levels for mAb2, the model helped elucidate that this effect was caused due to contribution from changes in glucose consumption, mAb secretion and temperature, instead of a direct impact of temperature alone on the kinetic rate of glycation.

Evaluation of an innovative mobile health programme for the self-management of chronic obstructive pulmonary disease (MH-COPD): protocol of a randomised controlled trial.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death globally. In outpatient care, the self-management of COPD is essential, but patient adherence to this remains suboptimal. The objective of this study is to examine whether an innovative mobile health (mHealth)-enabled care programme (MH-COPD) will improve the patient self-management and relevant health outcomes. METHODS AND ANALYSIS: A prospective open randomised controlled trial has been designed. In the trial, patients with COPD will be recruited from The Prince Charles Hospital, Brisbane, Australia. They will then be randomised to participate in either the MH-COPD intervention group (n=50 patients), or usual care control group (UC-COPD) (n=50 patients) for 6 months. The MH-COPD programme has been designed to integrate an mHealth system within a clinical COPD care service. In the programme, participants will use a mHealth application at home to review educational videos, monitor COPD symptoms, use an electronic action plan, modify the risk factors of cigarette smoking and regular physical activity, and learn to use inhalers optimally. All participants will be assessed at baseline, 3 months and 6 months. The primary outcomes will be COPD symptoms and quality of life. The secondary outcomes will be patient adherence, physical activity, smoking cessation, use of COPD medicines, frequency of COPD exacerbations and hospital readmissions, and user experience of the mobile app. ETHICS AND DISSEMINATION: The clinical trial has been approved by The Prince Charles Hospital Human Research Ethics Committee (HREC/16/QPCH/252). The recruitment and follow-up of the trial will be from January 2019 to December 2020. The study outcomes will be disseminated according to the Consolidated Standards of Reporting Trials statement through a journal publication, approximately 6 months after finishing data collection. TRIAL REGISTRATION NUMBER: ACTRN12618001091291.

Clinical management practices of life-threatening asthma: an audit of practices in intensive care.

OBJECTIVE: Lack of management guidelines for lifethreatening asthma (LTA) risks practice variation. This study aims to elucidate management practices of LTA in the intensive care unit (ICU). DESIGN: A retrospective cohort study. SETTING: Thirteen participating ICUs in Australia between July 2010 and June 2013. PARTICIPANTS: Patients with the principal diagnosis of LTA. MAIN OUTCOME MEASURES: Clinical history, ICU management, patient outcomes, ward education and discharge plans. RESULTS: Of the 270 (267 patients) ICU admissions, 69% were female, with a median age of 39 years (interquartile range [IQR], 26-53 years); 119 (44%) were current smokers; 89 patients (33%) previously required ICU admission, of whom 23 (25%) were intubated. The median ICU stay was 2 days (IQR, 2-4 days). Three patients (1%) died. Seventy-nine patients (29%) received non-invasive ventilation, with 11 (14%) needing subsequent invasive ventilation. Sixty-eight patients (25%) were intubated, with the majority of patients receiving volume cycled synchronised intermittent mechanical ventilation (n = 63; 93%). Drugs used included ß2-agonist by intravenous infusion (n = 69; 26%), inhaled adrenaline (n = 15; 6%) or an adrenaline intravenous infusion (n = 23; 9%), inhaled anticholinergics (n = 238; 90%), systemic corticosteroids (n = 232; 88%), antibiotics (n = 126; 48%) and antivirals (n = 22; 8%). When suitable, 105 patients (n = 200; 53%) had an asthma management plan and 122 (n = 202; 60%) had asthma education upon hospital discharge. Myopathy was associated with hyperglycaemia requiring treatment (odds ratio [OR], 31.6; 95% CI, 2.1-474). Asthma education was more common under specialist thoracic medicine care (OR, 3.0; 95% CI, 1.61-5.54). CONCLUSION: In LTA, practice variation is common, with opportunities to improve discharge management plans and asthma education.

Enhancing the functionality of a microscale bioreactor system as an industrial process development tool for mammalian perfusion culture.

Without a scale-down model for perfusion, high resource demand makes cell line screening or process development challenging, therefore, potentially successful cell lines or perfusion processes are unrealized and their ability untapped. We present here the refunctioning of a high-capacity microscale system that is typically used in fed-batch process development to allow perfusion operation utilizing in situ gravity settling and automated sampling. In this low resource setting, which involved routine perturbations in mixing, pH and dissolved oxygen concentrations, the specific productivity and the maximum cell concentration were higher than 3.0 × 106 mg/cell/day and 7 × 10 7 cells/ml, respectively, across replicate microscale perfusion runs conducted at one vessel volume exchange per day. A comparative analysis was conducted at bench scale with vessels operated in perfusion mode utilizing a cell retention device. Neither specific productivity nor product quality indicated by product aggregation (6%) was significantly different across scales 19 days after inoculation, thus demonstrating this setup to be a suitable and reliable platform for evaluating the performance of cell lines and the effect of process parameters, relevant to perfusion mode of culturing.

Molecular epidemiology of rotaviruses in the south-east Asian region from 2009 to 2015.

BACKGROUND: In Asia, rotavirus accounts for approximately 45% of admissions due to acute gastroenteritis in children <5 years, and causes about 145,000 deaths every year. We studied the distribution of rotavirus strains from Myanmar, Sri Lanka, and Nepal during 2009-2015. METHODS: Stool samples collected from children <5 years of age hospitalized with acute diarrhea in the three sites and positive for rotavirus antigen by enzyme immunoassay (EIA) were sent to the Christian Medical College, Vellore from 2009 to 2015. G and P typing of rotavirus strains were performed using reverse-transcription polymerase chain reaction (RT-PCR). RESULT: Of the 2354 EIA positive samples tested, G12P[8] (36.8%), G1P[8] (30.1%), and G12P[6] (41.3%) were the most common strains isolated from Myanmar, Sri Lanka, and Nepal respectively. CONCLUSION: There was substantial diversity of rotavirus genotypes, and continued surveillance in developing countries of Asia will help in understanding the epidemiology of rotavirus before and after introduction of vaccines.

Comparison of two-dose priming plus 9-month booster with a standard three-dose priming schedule for a ten-valent pneumococcal conjugate vaccine in Nepalese infants: a randomised, controlled, open-label, non-inferiority trial.

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.

Streptococcus pneumoniae carriage prevalence in Nepal: evaluation of a method for delayed transport of samples from remote regions and implications for vaccine implementation.

BACKGROUND: Pneumococcal disease is a significant cause of morbidity and mortality in young children in Nepal, and currently available pneumococcal conjugate vaccines offer moderate coverage of invasive disease isolates. METHODS: A prevalence study of children aged 1.5 to 24 months in urban and rural Nepal was conducted. In the urban group, nasopharyngeal swabs (NPS) were transported using silica desiccant packages (SDP) with delayed processing (2 weeks), or skim-milk-tryptone-glucose-glycerin (STGG) with immediate processing (within 8 hours). Pneumococcal nasopharyngeal carriage prevalence, serogroup/type distribution and isolate genotypes (as defined by multilocus sequence typing) were determined. RESULTS: 1101 children were enrolled into the study: 574 in the urban group and 527 in the rural group. Overall carriage prevalence based on culture from specimens transported and stored in STGG was 58.7% (337/574), compared to 40.9% (235/574) in SDP. There was concordance of detection of pneumococcus in 67% of samples. Using the SDP method, pneumococcal carriage prevalence was higher in the rural population (69.2%; 364/526) compared to the urban population (40.9%; 235/574). Serogroup/type distribution varied with geographical location. Over half of the genotypes identified in both the urban and rural pneumococcal populations were novel. CONCLUSION: The combination of delayed culture and transport using SDP underestimates the prevalence of pneumococcal carriage; however, in remote areas, this method could still provide a useful estimate of carriage prevalence and serogroup/type distribution. Vaccine impact is unpredictable in a setting with novel genotypes and limited serotype coverage as described here. Consequently, continued surveillance of pneumococcal isolates from carriage and disease in Nepali children following the planned introduction of pneumococcal conjugate vaccines introduction will be essential.

Bloodstream infection among children presenting to a general hospital outpatient clinic in urban Nepal.

BACKGROUND: There are limited data on the etiology and characteristics of bloodstream infections in children presenting in hospital outpatient settings in South Asia. Previous studies in Nepal have highlighted the importance of murine typhus as a cause of febrile illness in adults and enteric fever as a leading bacterial cause of fever among children admitted to hospital. METHODS: We prospectively studied a total of 1084 febrile children aged between 2 months and 14 years presenting to a general hospital outpatient department in Kathmandu Valley, Nepal, over two study periods (summer and winter). Blood from all patients was tested by conventional culture and by real-time PCR for Rickettsia typhi. RESULTS: Putative etiological agents for fever were identified in 164 (15%) patients. Salmonella enterica serovar Typhi (S. Typhi) was identified in 107 (10%), S. enterica serovar Paratyphi A (S. Paratyphi) in 30 (3%), Streptococcus pneumoniae in 6 (0.6%), S. enterica serovar Typhimurium in 2 (0.2%), Haemophilus influenzae type b in 1 (0.1%), and Escherichia coli in 1 (0.1%) patient. S. Typhi was the most common organism isolated from blood during both summer and winter. Twenty-two (2%) patients were PCR positive for R. typhi. No significant demographic, clinical and laboratory features distinguished culture positive enteric fever and murine typhus. CONCLUSIONS: Salmonella infections are the leading cause of bloodstream infection among pediatric outpatients with fever in Kathmandu Valley. Extension of immunization programs against invasive bacterial disease to include the agents of enteric fever and pneumococcus could improve the health of children in Nepal.

Evaluation of haemophilus influenzae type b vaccine for routine immunization in Nepali infants.

BACKGROUND: Haemophilus influenzae type b (Hib) carriage and disease studies in Nepali children suggest a significant burden of infection. Hib conjugate vaccines (HibCV) do not have uniform immunogenicity between populations. We determined the immunogenicity of HibCV in Nepali infants, before its introduction into the routine immunization schedule. METHODS: Ninety infants recruited at Patan Hospital, Kathmandu, received 3 doses of the HibCV with routine immunizations (diphtheria, tetanus, whole cell pertussis-hepatitis B vaccine + oral polio vaccine) at 6, 10 and 14 weeks of age, and a HibCV booster at 52 weeks. Anti-polyribosylribitol phosphate (PRP) concentrations were measured at 18, 52 and 56 weeks, and the antibody persistence at 52 weeks was compared with antibody values in unimmunized controls (n = 30). RESULTS: After 3 doses of primary immunizations, at 18 weeks of age (n = 74), all infants had anti-PRP concentrations above the accepted thresholds for short- and long-term protection (0.15 and 1.0 µg/mL, respectively). At 1 year of age, before administration of the booster of HibCV, the anti-PRP geometric mean antibody concentration was 2.76 µg/mL (confidence interval: 1.88-4.07) in sera from the immunized children compared with 0.11 µg/mL (95% confidence interval: 0.08-0.17) in the nonimmunized control group (n = 30). Twenty-seven percent (20/74) of participants, however, had anti-PRP concentrations <1.0 µg/mL. Four weeks after the booster dose of HibCV, 98.5% of infants had anti-PRP concentrations above 1.0 µg/mL. CONCLUSION: Immunization with HibCV given as part of the Expanded Program on Immunization schedule in Nepal elicits robust antibody responses. Though the antibody wanes during the first year of life, most 1-year-old infants remain protected and respond robustly to a booster dose of the vaccine.