Does the implementation of revised American College of Cardiology and American Heart Association (ACC/AHA) guidelines improve the identification of stillbirths and preterm births in hypertensive pregnancies: a population-based cohort study from South Asia and sub-Saharan Africa.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a significant cause of maternal mortality worldwide. The classification and treatment of hypertension in pregnancy remain debated. We aim to compare the effectiveness of the revised 2017 ACC/AHA blood pressure threshold in predicting adverse pregnancy outcomes. METHODS: We conducted a secondary data analysis of the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository study, including 10,001 pregnant women from Bangladesh, Pakistan, and Tanzania. Blood pressure was measured using validated devices at different antenatal care visits. The blood pressure readings were categorized as: normal blood pressure (systolic blood pressure (sBP) < 120 mm Hg and diastolic blood pressure (dBP) < 80 mm Hg), elevated blood pressure (sBP 120-129 and dBP < 80), stage 1 hypertension (sBP 130-139 or dBP 80-89, or both), and stage 2 hypertension (sBP ≥ 140 or dBP ≥ 90, or both). We estimated risk ratios for stillbirths and preterm births, as well as diagnostic test properties of both the pre-existing JNC7 (≥ 140/90) and revised ACC/AHA (≥ 130/80) thresholds using normal blood pressure as reference group. RESULTS: From May 2014 to June 2018, blood pressure readings were available for 9,448 women (2,894 in Bangladesh, 2,303 in Pakistan, and 4,251 in Tanzania). We observed normal blood pressure in 70%, elevated blood pressure in 12.4%, stage 1 hypertension in 15.2%, and stage 2 hypertension in 2.5% of the pregnant women respectively. Out of these, 310 stillbirths and 9,109 live births were recorded, with 887 preterm births. Using the ACC/AHA criteria, the stage 1 hypertension cut-off revealed 15.3% additional hypertension diagnoses as compared to JNC7 criteria. ACC/AHA defined hypertension was significantly associated with stillbirths (RR 1.8, 95% CI 1.4, 2.3). The JNC 7 hypertension cut-off of ≥ 140/90 was significantly associated with a higher risk of preterm births (RR 1.6, 95% CI 1.2, 2.2) and stillbirths (RR 3.6, 95% CI 2.5, 5.3). Both criteria demonstrated low sensitivities (8.4 for JNC-7 and 28.1 for ACC/AHA) and positive predictive values (11.0 for JNC7 and 5.2 for ACC/AHA) in predicting adverse outcomes. CONCLUSION: The ACC/AHA criteria (≥ 130/80) identified additional cases of hypertension but had limited predictive accuracy for stillbirths and preterm births, highlighting the ongoing need for improved criteria in managing pregnancy-related hypertension.

Management of iron deficiency anemia during pregnancy: a midwife-led continuity of care model.

Background: Globally, 36.5% of pregnancies are affected by anemia, particularly in low-and middle-income countries, posing significant risks to maternal and perinatal health. In rural Pakistan, 44.3% of pregnant women suffer from iron deficiency, contributing to the high prevalence of anemia. Limited accessibility to antenatal care exacerbates the challenge, necessitating innovative solutions. This study assessed a midwife-led continuity of care model, utilizing intravenous (IV) iron therapy for the management of anemia in Karachi, Pakistan. Methods: We performed a retrospective analysis of data from a prospective cohort study conducted in two primary healthcare facilities, which employed a community midwife (CMW)-led continuity of care model for antenatal care, including IV iron therapy. We extracted data from February 2021 to March 2022 for women who were diagnosed with anemia based on hemoglobin (Hb) levels, categorized as mild (10.0 to 10.9 g/dL), moderate (7.0 to 9.9 g/dL), or severe (less than 7.0 g/dL). Assessment occurred at the initial antenatal care (ANC) visit to establish baseline anemia severity, and approximately 2 weeks after intravenous (IV) iron therapy administration to evaluate post-treatment changes were considered. Results: We enrolled 114 pregnant women, where the majority presented with moderate (88.6%) anemia. After IV iron treatment, 48.5% improved to normal-mild levels, while 50% remained unchanged. Severe anemia affected 10.5% at baseline; 42% shifted to moderate and 50% to normal-mild post-treatment, with one remaining unchanged (p < 0.001). Among women enrolled in the first and second trimesters, severe anemia improved to normal-mild (50%) and moderate levels (50%) (pre-treatment: n = 10, post-treatment: n = 0), and moderate anemia decreased by 48% (pre-treatment: n = 92, post-treatment: n = 47). Conclusion: Our midwife-led model of care demonstrated an improvement in iron levels among pregnant women. The model addressed the challenges of anemia prevalence in Pakistan and underscored the significance of empowering front-line healthcare providers, such as community midwives (CMWs) for managing these common conditions.

Neurodevelopmental outcomes following possible serious bacterial infection in early infancy in Karachi, Pakistan: a prospective cohort study.

BACKGROUND: Pakistan reports a significant burden of neonatal mortality, with infections as one of the major causes. We aim to assess the long-term impact of early infancy infections on neurodevelopmental outcomes during later childhood. METHODS: We conducted a prospective follow-up study of the cohort enrolled at the Karachi site of the Aetiology of Neonatal Infection in South Asia (ANISA) during 2019-2020. Children with a possible serious bacterial infection (based on the WHO IMCI algorithm) at early infancy were assessed for neurodevelopment at 6-9 years of age and compared with healthy controls. The Ten Questions (TQS) questionnaire, Strengths and Difficulties Questionnaire (SDQ), and Parent's Evaluation of Developmental Stage Assessment Level (PEDS: DM-AL) neurodevelopmental assessment tools, were administered and scored by the research staff who were blinded to the child's exposure status. Generalized Structural Equation Modelling (GSEM) was employed to verify relationships and associations among developmental milestones, anthropometry, and sociodemographic variables. RESULTS: A total of 398 children (241 cases and 157 controls) completed neurodevelopmental and growth assessments. Cases had a significantly higher rate of abnormal TQS scores (54.5% vs. 35.0%, p-value 0.001), greater delays in motor milestones (21.2% vs. 12.1%, p-value 0.02), lower fine motor skills (78.4 ± 1.4 vs. 83.2 ± 1.5, p-value 0.02). The receptive language skills were well-developed in both groups. According to the logistic regression model, exposure to infection during the first 59 days of life was associated with delayed TQS milestones (ß = -0.6, 95% CI -1.2,-0.04), TQS hearing domain (ß = -0.3, 95% CI: -1.2 to 0.7), PEDS: DM-AL fine motor domain (ß = -1.3, 95% CI: -4.4 to 1.7), PEDS: DM-AL receptive language development (ß = -1.1, 95% CI: -3.7 to 1.4) and child anthropometric measurements such as weight and height (ß = -0.2, 95% CI: -0.4 to 0.01 and ß = -0.2, 95% CI: -0.4 to -0.01, respectively). Early pSBI exposure was positively associated with PEDS: DM-AL self-help domain (ß = 0.6, 95% CI: -1.2 to 2.4) and SDQ-P overall score (ß = 0.02, 95% CI: -0.3 to 0.3). CONCLUSION: Children exposed to PSBI during early infancy have higher rates of abnormal development, motor delays, and lower fine motor skills during later childhood in Pakistan. Socioeconomic challenges and limited healthcare access contribute to these challenges, highlighting the need for long-term follow-ups with integrated neurodevelopment assessments.

Predictors of Respiratory Syncytial Virus, Influenza Virus, and Human Metapneumovirus Carriage in Children Under 5 Years With WHO-Defined Fast-Breathing Pneumonia in Pakistan.

BACKGROUND: Pneumonia is a leading cause of morbidity and mortality in children < 5 years. We describe nasopharyngeal carriage of respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza virus among children with fast-breathing pneumonia in Karachi, Pakistan. METHODS: We performed a cross-sectional analysis of nasopharyngeal swabs from children aged 2-59 months with fast-breathing pneumonia, enrolled in the randomized trial of amoxicillin versus placebo for fast-breathing pneumonia (RETAPP) (NCT02372461) from 2014 to 2016. Swabs were collected using WHO standardized methods, processed at the Aga Khan University, Pakistan. Viral detection was performed using LUMINEX xTAG respiratory viral panel assay and logistic regression identified clinical and sociodemographic predictors. FINDINGS: Of the 1000 children tested, 92.2% (n = 922) were positive for viral carriage. RSV, hMPV, and influenza virus were detected in 59 (6.4%), 56 (6.1%), and 58 (6.3%) children and co-infections in three samples (two RSV-hMPV and one influenza-hMPV). RSV carriage was common in infants (56%), we observed a higher occurrence of fever in children with hMPV and influenza virus (80% and 88%, respectively) and fast breathing in RSV (80%) carriage. RSV carriage was positively associated with a history of fast/difficulty breathing (aOR: 1.96, 95% CI 1.02-3.76) and low oxygen saturation (aOR: 2.52, 95% CI 1.32-4.82), hMPV carriage was positively associated with a complete vaccination status (aOR: 2.22, 95% CI 1.23-4.00) and body temperature ≥ 37.5°C (aOR: 2.34, 95% CI 1.35-4.04) whereas influenza viral carriage was associated with body temperature ≥ 37.5°C (aOR: 4.48, 95% CI 2.53-7.93). CONCLUSION: We observed a high nasopharyngeal viral carriage among children with WHO-defined fast-breathing pneumonia in Pakistan. Fever, difficulty in breathing, hypoxia and vaccination status are important clinical predictors for viral nonsevere community-acquired pneumonia.

Secondary attack rates and determinants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) household transmission in Pakistan: A case-ascertained prospective, longitudinal study.

BACKGROUND: Households are considered ideal settings for studying the transmission dynamics of an infectious disease. METHODS: A prospective study was conducted, based on the World Health Organization FFX protocol from October 2020 to January,2021. Household contacts of laboratory-confirmed index cases were followed up for their symptomatic history, nasal swabs for RT-PCR,and blood samples for anti-SARS CoV-2 antibodies were collected at enrollment and days 7, 14 and 28. We estimated secondary attack rate (SAR), effective household case cluster size and determinants of secondary infection among susceptible household contacts using multivariable logistic regression. RESULTS: We enrolled 77 index cases and their 543 contacts. Out of these, 252 contacts were susceptible at the time of enrollment. There were 77 household clusters, out of which, transmission took place in 20 (25.9%) giving rise to 34 cases. The acquired secondary attack rate (SAR) was 14.0% (95% CI 9.0-18.0). The effective household case cluster size was 0.46 (95%CI 0.33,0.56). Reported symptoms of nausea and vomiting (aOR, 7.9; 95% CI, 1.4-45.5) and fatigue (aOR, 9.3; 95% CI, 3.8-22.7) were associated with SARS-CoV-2 transmission. CONCLUSIONS: We observed a low SARS-CoV-2 secondary attack rate in the backdrop of high seroprevalence and asymptomatic transmission among households in Karachi, Pakistan.

Early to mid-pregnancy HbA1c levels and its association with adverse pregnancy outcomes in three low middle-income countries in Asia and Sub-Saharan Africa.

BACKGROUND: Hyperglycemia during pregnancy leads to adverse maternal and fetal outcomes. Thus, strict monitoring of blood glucose levels is warranted. This study aims to determine the association of early to mid-pregnancy HbA1c levels with the development of pregnancy complications in women from three countries in South Asia and Sub-Saharan Africa. METHODS: We performed a secondary analysis of the AMANHI (Alliance for Maternal and Newborn Health Improvement) cohort, which enrolled 10,001 pregnant women between May 2014 and June 2018 across Sylhet-Bangladesh, Karachi-Pakistan, and Pemba Island-Tanzania. HbA1c assays were performed at enrollment (8 to < 20 gestational weeks), and epidemiological data were collected during 2-3 monthly household visits. The women were followed-up till the postpartum period to determine the pregnancy outcomes. Multivariable logistic regression models assessed the association between elevated HbA1c levels and adverse events while controlling for potential confounders. RESULTS: A total of 9,510 pregnant women were included in the analysis. The mean HbA1c level at enrollment was found to be the highest in Bangladesh (5.31 ± 0.37), followed by Tanzania (5.22 ± 0.49) and then Pakistan (5.07 ± 0.58). We report 339 stillbirths and 9,039 live births. Among the live births were 892 preterm births, 892 deliveries via cesarean section, and 532 LGA babies. In the multivariate pooled analysis, maternal HbA1c levels of ≥ 6.5 were associated with increased risks of stillbirths (aRR = 6.3, 95% CI = 3.4,11.6); preterm births (aRR = 3.5, 95% CI = 1.8-6.7); and Large for Gestational Age (aRR = 5.5, 95% CI = 2.9-10.6). CONCLUSION: Maternal HbA1c level is an independent risk factor for predicting adverse pregnancy outcomes such as stillbirth, preterm birth, and LGA among women in South Asia and Sub-Saharan Africa. These groups may benefit from early interventional strategies.

Knowledge, attitudes, and practices toward seasonal influenza vaccination among healthcare workers and pregnant women in Pakistan: A mixed methods approach.

Vaccine hesitancy is a significant public health issue globally. We aim to document the barriers toward seasonal influenza vaccine uptake among healthcare workers (HCWs) and pregnant women (PW) in Pakistan. We performed a concurrent mixed methods study in four cities (Karachi, Islamabad, Quetta, and Peshawar) across Pakistan from September to December 2021. The quantitative component consisted of independent cross-sectional surveys for PW and HCWs, and the qualitative component comprised of in-depth interviews (IDIs) and focus group discussions (FGDs) among HCWs. Simple linear regression was used to determine the association of sociodemographic variables with knowledge, attitudes, and practices. Overall, 750 PW and 420 HCWs were enrolled. Among the PW, 44% were willing to receive the vaccine if available free of cost. Only 44% of the HCWs were vaccinated; however, 86% intended to get vaccinated and were willing to recommend the vaccine to their patients. HCWs refused vaccine due to side-effects (65%), cost (57%), and allergies (36%). An education level of secondary school and above was predictive of higher attitude and knowledge scores while having received the COVID-19 vaccine was associated with higher practice scores for both PW and HCWs. Several themes emerged from the interviews: 1) HCWs' knowledge of influenza and its prevention, 2) HCWs' perception of motivators and barriers to influenza vaccine uptake and 3) HCWs' attitudes towrd vaccine promotion. We report low influenza vaccine coverage among HCWs and PW in Pakistan. Educational campaigns addressing misconceptions, and improving affordability and accessibility through government interventions, can improve vaccine uptake.

Co-carriage of Staphylococcus aureus and Streptococcus pneumoniae among children younger than 2 years of age in a rural population in Pakistan.

Objectives: Staphylococcus aureus and Streptococcus pneumoniae are common colonizers of the human nasopharynx. In this study, we describe S. aureus nasopharyngeal carriage and evaluate its association with S. pneumoniae carriage post-10-valent pneumococcal conjugate vaccine (PCV10) introduction in Pakistan. Methods: A serial cross-sectional study was undertaken from 2014 to 2018, children <2 years were randomly selected, and nasopharyngeal swabs were collected using standard WHO guidelines. S. aureus and S. pneumoniae isolates were identified using standard methods and tested for antimicrobial susceptibility by the standard Kirby-Bauer disk-diffusion method as per Clinical & Laboratory Standards Institute (CLSI) recommendations. Regression analysis was used to determine predictors associated with S. aureus carriage. Results: We enrolled 3140 children. S. aureus carriage prevalence was 5.6% (176/3140), and 50.1% (81/176) of the isolates were methicillin-resistant S. aureus (MRSA). S. aureus carriage was higher in the absence of pneumococcus compared to isolates in which pneumococcus was present (7.5% vs 5.0%). S. aureus carriage was negatively associated with pneumococcal carriage, being in 3rd and 4th year of enrollment, and vaccination with two and three PCV10 doses, in addition, fast breathing, ≥2 outpatients visits, and rainy season were positively associated. The following resistance rates were observed: 98.9% for penicillin, 74.4% for fusidic acid, and 23.3% for gentamicin, 10.2% for erythromycin, and 8.5% for cotrimoxazole. All isolates were susceptible to amikacin. Conclusions: Overall S. aureus carriage prevalence was low, PCV10 vaccine was protective against the carriage. The proportion of MRSA carriage and antimicrobial resistance was high in this community warranting continuous monitoring for invasive infections.

Knowledge, attitudes, and practices towards seasonal influenza vaccination among pregnant women and healthcare workers: A cross-sectional survey in Afghanistan.

Background: Despite recommendation by the World Health Organization (WHO), influenza vaccination coverage among high-risk groups remains suboptimal in Afghanistan. This study aims to document the knowledge, attitudes, and practices of seasonal influenza vaccine uptake among two priority groups, pregnant women (PWs) and healthcare workers (HCWs). Methods: This cross-sectional study enrolled PWs and HCWs in Kabul, Afghanistan, from September to December 2021. Data on vaccine intention and uptake, knowledge, and attitudes towards vaccination were collected. Simple linear regression was used to predict the impact of sociodemographic characteristics on the KAP score. Results: A total of 420 PWs were enrolled in Afghanistan. The majority (89%) of these women had never heard of the influenza vaccine but 76% intended to receive the vaccine. Of the 220 HCWs enrolled, 88% were unvaccinated. Accessibility and cost were factors which encouraged vaccination among HCWs. Fear of side effects and affordability were identified as key barriers. HCWs reported high level of vaccine intention (93%). PWs aged under 18 years (ß: 6.5, P = 0.004), between 18 and 24 years (ß: 2.9, P = 0.014), currently employed (ß: 5.8, P = 0.004), and vaccinated against COVID-19 (ß: 2.8, P = 0.01) were likely to have a higher attitude score. Among HCWs, being female was a predictor for poor vaccination practice (ß: -1.33, P < 0.001) whereas being vaccinated against COVID-19 was a predictor for higher practice score (ß: 2.4, P < 0.001). Conclusion: To increase influenza vaccination coverage among priority groups, efforts should be made to address issues such as lack of knowledge, limited availability, and cost barriers.

Differential coverage for vaccines in the expanded program on immunization (EPI) among children in rural Pakistan.

BACKGROUND: Pakistan has a well-established Expanded Program on Immunization (EPI) however vaccine-preventable diseases still account for high infant and child mortality rates. This study describes the differential vaccine coverage and determinants of vaccine uptake in rural Pakistan. METHODS: From October 2014 to September 2018, we enrolled children younger than 2 years of age from the Matiari Demographic Surveillance System in Sindh, Pakistan. Socio-demographic and vaccination history were collected from all participants. Vaccine coverage rates and timeliness were reported. Socio-demographic variables for missed and untimely vaccination were studied in multivariable logistic regression. RESULTS: Of the 3140 enrolled children, 48.4 % received all EPI recommended vaccines. Only 21.2 % of these were age appropriate. Around 45.4 % of the children were partially vaccinated, and 6.2 % were unvaccinated. Highest coverage was seen for the first dose of pentavalent (72.8 %), 10-valent Pneumococcal Conjugate Vaccine (PCV10) (70.4 %) and Oral Polio Vaccine (OPV) (69.2 %) and the lowest coverage was for measles (29.3 %) and rotavirus (1.8 %) vaccines. Primary caretakers and wage earners with a higher level of education were protective against missed and untimely vaccination. Enrollment in the 2nd, 3rd and 4th study year was negatively associated with being unvaccinated whereas distance from a major road was positively associated with non-adherence to schedule. CONCLUSION: Vaccine coverage was low among children in Matiari, Pakistan, and majority received delayed doses. Parents' education status and year of study enrollment was protective against vaccine dropout and delayed vaccination whereas geographical distance from a major road was a predictor. Vaccine promotion and outreach efforts may have had a beneficial impact on vaccine coverage and timeliness.

Long-Term Use Of Inhaled Hypertonic Saline In Children And Adolescents With Cystic Fibrosis: Experience From A Tertiary Care Center In A Low And Middle Income Country.

Background: Long term hypertonic saline use has been found to improve mucus transport, airway hydration, and mucociliary clearance in patients with cystic fibrosis. However, the effect of hypertonic saline on the outcomes of patients with cystic fibrosis is not well established. The aim of our study was to determine the long-term use of hypertonic saline in reducing pulmonary exacerbations, length of hospital stay and pseudomonas colonization in patients with cystic fibrosis admitted for treatment at a tertiary care referral center. Methods: Retrospective cohort study was conducted on 71 patients with cystic fibrosis. Patients ranged in age between 3-18 years. All patients with two to five pulmonary exacerbations in the preceding six months were included in the study. Those who received regular inhaled 3-7% hypertonic saline twice daily during their admission and till 6 months after discharge from hospital were categorized as hypertonic saline (HTS) group. Patients who did not receive regular hypertonic saline for 6 months were included in the non-hypertonic saline (NHTS) group. Data was analyzed at the end of one year. Results: The HTS group had 37 patients whereas, the NHTS group had 34 patients. Mean number of exacerbation episodes was significantly lower in HTS group (2.18±0.84) as compared to NHTS group (3.67±0.91) (p<0.01) whereas, length of hospital stays and frequency of pseudomonas colonization did not significantly differ between the two groups (p=0.78 and p=0.12 respectively). The mean number of pulmonary exacerbations also significantly reduced from 3.11±1.07 to 2.18±0.84 p-value <0.01 in the HTS group over the follow-up period of one year. Conclusion: : Long term hypertonic saline therapy is beneficial in patients with cystic fibrosis in preventing pulmonary exacerbations and subsequently reducing morbidity.

Use of systemic steroids during pulmonary exacerbations in children and adolescent with Cystic fibrosis.

OBJECTIVE: To determine the role of systemic steroids in cystic fibrosis patients and its effects on pulmonary exacerbation in children and adolescents. METHODS: The retrospective cohort study was conducted at the Aga Khan University Hospital, Karachi, and comprised data from January 2015 to December 2019 of cystic fibrosis patients aged 3-18 years hospitalised with pulmonary exacerbations. The patients were divided into systemic steroid group A and non-systemic steroid group B. Patients in group A received parenteral steroids during acute exacerbation of cystic fibrosis in the first two weeks of admission, while those in group B did not receive systemic steroids. Length of hospital stay and number of days on oxygen support were compared between the groups. Data was analysed using SPSS 22. RESULTS: Of the 124 patient charts evaluated, 84(67.7%) were included; 40(47.6%) in group A and 44(52.4%) in group B. There were no significant differences between the groups related to age, age at diagnosis, weight, height, and pulmonary exacerbations (p>0.05). Group A had significantly fewer days on oxygen support compared to group B (p<0.001), but there was inter-group difference in mean length of hospital stay (p=0.53). CONCLUSIONS: Systemic steroid usage during hospitalisation for acute exacerbation of cystic fibrosis was associated with decreased duration of oxygen requirement with standard treatment.

Pneumococcal Carriage in Infants Post-PCV10 Introduction in Pakistan: Results from Serial Cross-Sectional Surveys.

The 10-valent pneumococcal vaccine was introduced in Pakistan's Expanded Program on Immunization (EPI) in 2013 as a 3 + 0 schedule without catchup. We conducted three annual cross-sectional surveys from 2014−2016 to measure vaccine-type (VT) carriage in infants from a rural part of Pakistan. Nasopharyngeal specimens were collected by random sampling of infants from two union councils of Matiari. Samples were then transported to the Infectious Disease Research Laboratory (IDRL) at the Aga Khan University within 6−8 h of collection. Serotypes were established using sequential multiplex PCR. Of the 665 children enrolled across three surveys, 547 were culture-positive for pneumococcus. VT carriage decreased from 21.8% in 2014 to 12.7% in 2016 (p-value for trend <0.001). Those who were not vaccinated or partially vaccinated were found to be at higher risk of carrying a VT serotype ((aOR 2.53, 95% CI 1.39, 4.63 for non-vaccinated) and (aOR 3.35, 95% CI 1.82, 6.16 for partially vaccinated)). On the other hand, being enrolled in the most recent survey was negatively associated with VT carriage (aOR 0.51, 95% CI 0.28, 0.93). We found that PCV10 was effective in decreasing the carriage of vaccine-type serotypes in Pakistani infants.

Serotype-specific effectiveness against pneumococcal carriage and serotype replacement after ten-valent Pneumococcal Conjugate Vaccine (PCV10) introduction in Pakistan.

OBJECTIVE: Pakistan was one of the first South-Asian countries to introduce the ten-valent pneumococcal conjugate vaccine (PCV10) at the national level, using a 3+0 schedule without catchup, in 2013. METHODS: From 2014-18, fifteen children <2 years old were recruited every week in Matiari, Sindh, and nasopharyngeal swabs were collected. The samples were cultured, and pneumococcus was further serotyped through multiplex PCR at the Aga Khan University Hospital as per the method described by the Centers for Disease Control and Prevention, USA. RESULTS: Pneumococcus was detected in 2370/3140 (75%) children. Vaccine type (VT) and non-vaccine type (NVT) serotypes were carried by 379 and 1990 children. There was a significant decline in VT carriage (by 40.3%, p-value <0.001), whereas overall NVT carriage remained the same. The prevalence of VT serotypes 6B, 9V/9A, and 19F showed a significant decline by 58.8%, 79.3%, and 56%, respectively. The prevalence of NVT serotypes 19A, 21, and 10A increased by 70%, 33.3%, and 65.6%, respectively, whereas serotypes 13 and 9N/9L decreased by 53.4% and 51.8%, respectively. Serotype-specific vaccine effectiveness estimates that reached statistical significance were for 9V/9A (VE = 65.0, 95% CI 26.0-83.5%), 19F (VE = 55.3, 95% CI 15.5-76.4%) and for the vaccine related serotype 6A (VE = 28.4, 95% CI 0.9-48.2%). CONCLUSION: The emergence of NVT serotypes, primarily 19A replacing VT serotypes in this rural community, necessitates continuous monitoring of serotypes in the carriage and invasive disease to evaluate the utility of existing vaccine formulations.

Characteristics of electrolyte imbalance and pseudo-bartter syndrome in hospitalized cystic fibrosis children and adolescents.

INTRODUCTION: Pseudo-Bartter syndrome (PBS) is a rare manifestation of Cystic fibrosis (CF) and can often be the initial presentation in these patients, however, due to significantly overlapping symptoms it is often misdiagnosed as simple dehydration or Bartter syndrome. The objective of our study was to highlight the key features of PBS and electrolyte imbalance in CF patients helping in early and prompt diagnosis. METHOD: We performed a retrospective study from January 2015 to December 2019 at the Aga Khan University Hospital (AKUH), Pakistan. CF patients aged from 1-18 years, admitted at AKUH were enrolled and their laboratory data and individual charts were reviewed. Patients were categorized into three groups based on their serum electrolyte profile and their clinical findings were compared. RESULT: We enrolled 72 CF patients, out of which 42 (58%) were categorized into the Normal Electrolyte (NE) group, 19 (26%) into the Electrolyte Imbalance (EI) group and 11 (15%) in the PBS group. Out of 11 cases, 6 (54.54%) patients in PBS group presented with features consistent with PBS leading to CF diagnosis labeled as "early presenters". Mean age of patients in the PBS group was 3.81± 0.86 years and their age at diagnosis were significantly lower as compared to other groups. Gastrointestinal disturbances including diarrhea, vomiting and constipation were more common in the EI and PBS groups. Polyuria was most common in the PBS (72%) group. Length of hospital stay showed no significant difference. CONCLUSION: Pseudo-Bartter syndrome can be a presenting feature of cystic fibrosis. Electrolyte imbalance should be anticipated in hospitalized CF children and adolescent.

Antimicrobial Resistance in Pneumococcal Carriage Isolates from Children under 2 Years of Age in Rural Pakistan.

Antimicrobial resistance is an emerging public health concern. Ten-valent pneumococcal vaccine (PCV10) was introduced in Pakistan's Expanded Program on Immunization (EPI) in 2012 as a 3 + 0 schedule without catchup. From 2014 to 2018, children <2 years were randomly selected in two rural union councils of Matiari, Pakistan. Nasopharyngeal swabs were collected using standard WHO guidelines by trained staff and processed at Infectious Disease Research Laboratory at The Aga Khan University, Karachi using culture on sheep blood agar and Multiplex PCR methods described by CDC, USA. Pneumococcal isolates were identified by optochin sensitivity and bile solubility tests. Isolates were then tested for antimicrobial susceptibility by standard Kirby-Bauer disk-diffusion method on Mueller-Hinton Agar (MHA) with 5% sheep blood agar as per Clinical & Laboratory Standards Institute (CLSI) recommendations. Of 3140 children enrolled, pneumococcal isolates were detected in 2370 (75%). Vaccine coverage improved from 41% to 68.4%. Out of the 2370 isolates, 88.4%, 37.6% and 25% were resistant to cotrimoxazole, tetracycline and erythromycin, respectively. There was no resistance to penicillin, ceftriaxone, and vancomycin. For erythromycin, resistance increased from 20% in 2014/15 to 30.8% in 2017/18 and for tetracycline it increased from 34.9% to 41.8% both of which were explained by an increase in prevalence of serotype 19A. Pneumococcal isolates were susceptible to penicillin, ceftriaxone, and vancomycin. They were largely resistant to cotrimoxazole and tetracycline. There was an increase in erythromycin and tetracycline resistance attributed to increasing prevalence of serotype 19A. Pneumococcal isolates from carriage and invasive disease should be closely monitored for antimicrobial susceptibility. IMPORTANCE Antimicrobial resistance is an emerging public health concern particularly in low- and middle-income countries where there is poor regulation and easy availability of antibiotics. This is the first study from Pakistan to report antimicrobial resistance patterns of pneumococcus after vaccine introduction in the community. Pakistan was the first South-Asian country to introduce PCV10 in its Expanded Program on Immunization (EPI) in 2012 as a 3 + 0 schedule without catchup. In this study, we describe the PCV10 impact on antimicrobial resistance patterns of pneumococcal nasopharyngeal carriage in children younger than 2 years of age in a rural district in Pakistan after the introduction of the vaccine.

Spectrum Of Pulmonary Exacerbation In Children And Adolescent With Cystic Fibrosis And Physicians' Practices: Experience From Tertiary Care Center From Lower-Middle Income Country.

BACKGROUND: Pulmonary exacerbations (PEx) are major contributor of significant morbidity and mortality in CF patients. Managing PEx needs standardization and without standard local practice guidelines there will be significant variation in practice in managing these children. The aim of this study is to analyse the clinical management of PEx in our setup and to document variation in practices among physicians. METHODS: Children and adolescents ≤18 years with CF pulmonary exacerbations admitted at high dependency unit (HDU) or wards were included in the study. Frequencies of different intravenous antibiotic combinations were documented along with use of different inhaled antibiotics and inhalation therapy. Practices of different physician were further studied with regards to use of systemic steroids, oral azithromycin and inhaled antibiotics. One way ANOVA was used to assess differences between physicians' practices. RESULTS: Fifty-seven patients were selected according to the inclusion criteria for 114 different exacerbations. Mean pulmonary exacerbation (PEx) for a patient (events/person-year) over five years was 3.16±1.41 per year and average length of stay was 5.7±4.4 days. Combination of intravenous ceftazidime and amikacin was the most frequently used regimen (28.07%). Five different physicians dealing with majority of the exacerbations (n=74) were studied further. Variability among consultants was significant in using systemic steroids (21.42-92.30%), use of maintenance oral azithromycin (0- 80%) and inhaled antibiotics (0-86.6%). CONCLUSIONS: Significant variation exists in practices of physicians dealing with CF PEx. Variability observed in our study will definitely provide openings for local CF experts to come up with standardized inpatient exacerbation guidelines.

Methods for estimating the direct and indirect effect of 10 valent pneumococcal vaccine on nasopharyngeal carriage in children under 2 years in Matiari, Pakistan.

Pneumonia is the leading cause of morbidity and mortality in children worldwide. The ten valent pneumococcal vaccine (PCV10) was introduced in Pakistan's Expanded Program on Immunization (EPI) in 2012 as a 3 + 0 schedule without catchup immunization. Nasopharyngeal carriage is taken as a surrogate marker to measure the impact of pneumococcal vaccine on populations. Carriage surveys are necessary to monitor the persistence of Vaccine Type (VT) serotypes, the emergence of Non-Vaccine Type (NVT) serotypes, and their role in both transmission and disease. This article describes various troubleshooting measures which we undertook to adopt the protocol to our setting. We also used an innovative approach to describe various epidemiological parameters of vaccine effectiveness against carriage. It is important to publish these methods to allow for valid regional and temporal comparisons of results in different settings. Thus, in this article, we describe the following methods for isolating upper airway pneumococcal carriage:•Methods for the collection, transport, and storage of nasopharyngeal samples.•Methods for identification and serotyping of pneumococci.•Methods for estimation of the direct and indirect effects of pneumococcal vaccines on nasopharyngeal carriage.