In children younger than two years, most surgeons perform the inguinal herniotomy superficially through the external ring, a technique known as Mitchell-Banks’ Herniotomy (MBH) while in older children, commonly Ferguson and Gross Herniotomy (FGH) is performed which involves opening of inguinal canal. Our aim was to compare the FGH and MBH in terms of recurrence in boys with inguinal hernia.Boys with inguinal hernia presenting to Pediatric Surgery, Mayo Hospital Lahore from Dec 2016 to January 2018 were included in the study, if older than two years and younger than 14 years and without palpable deep ring (2 cm or more in width) or strangulation of inguinal hernia or malnutrition. They were randomly allocated in 2 groups after obtaining informed consent from parents, and underwent MBH (Group-A) and FGH (Group-B). Children were called for follow up after 1 week and at 6 months to assess for recurrence.Total 260 patients with inguinal hernia were enrolled (NCT: 03392636). The mean age of boys in Group-A was 5.2±3.0 years and in Group-B was 5.9±3.1 years. Mean operating time in Group-A (26.65±3.22 minutes) was longer than Group-B (15.92±4.22 minutes), and scrotal oedema was noted in 38 (29.2%) cases in Group-A, while 7 (5.4%) cases in Group-B. Testicular atrophy was noted in one patient of Group-B. Recurrence occurred in 1(0.8%) patient in Group-A, and in 8(6.2%) patients in Group-B .Mitchell-Banks’ herniotomy has lower recurrence rate than Ferguson and Gross Herniotomy in boys older than two years. Inguinal herniotomy is one of the most commonly performed procedure by a pediatric surgeon. The reported incidence of inguinal hernia in mature infants varies from 1-5% to 12-25% with a family history, and a male preponderance. It is slightly higher in pre-mature infants about 10-30%. In children, it is almost always indirect inguinal hernia caused by patent processus vaginalis. Right sided hernias are twice as common as those on the left and bilateral hernias are present approximately 10% of the times.3The basic principle of herniotomy for indirect inguinal hernia is the ligation of processus vaginalis as described by Marcy in 1871.8Ferguson and Gross herniotomy (FGH) and Mitchell-Banks’ herniotomy (MBH) are the two most commonly performed open methods of pediatric inguinal herniotomy. FGH involves opening of inguinal canal and herniotomy at the level of internal inguinal ring or at the level of pre-peritoneal fat. In contrast, in MBH, the same is accomplished without opening inguinal canal. Traditional teaching for inguinal herniotomy is to do MBH in children under the age of two years and FGH in older children.11Most common cause of a recurrent inguinal hernia in children is failure to identify or to completely ligate the indirect inguinal hernial sac at the level of internal ring or pre-peritoneal fat.9The objective of this study was to compare the recurrence rate between the two different procedures of inguinal herniotomy in boys older than two years. Rationale was that no randomized trial is available to compare the two techniques and if the recurrence rates are comparable, then MBH can be recommended as in this technique, there is minimum distortion of anatomy.This randomized controlled trial  was carried out in the department of Pediatric Surgery, King Edward Medical University/ Mayo Hospital Lahore from December 2016 to January 2018. Sample size of 260 cases (130 in each group), was calculated with 95% confidence level, 80% power of test with expected percentage of recurrence of MBH as 0% and FGH as 6% using formula:13INLINENon probability convenience sampling technique was used. All boys aged between 2-14 years presenting in Pediatric Surgery Department, Mayo Hospital Lahore with inguinal hernia were included. Exclusion criteria was children who were severely malnourished, children with very large hernia needing internal ring repair , children with sliding hernia  or strangulated hernia . Children with connective tissue disorders or undescended testis or associated hydrocele were also excluded.After taking informed consent from parents, children fulfilling the criteria were randomly allocated in two groups via lottery method. Children in Group-A (Case) underwent Mitchell Banks Herniotomy and those in Group-B (Control) underwent Ferguson and Gross Herniotomy.Under aseptic measures, inguinal skin cease incision was made in both procedures. In MBH, inguinal herniotomy was done through the superficial inguinal ring, by dissecting the hernia sac from vas deferens and vessels without opening inguinal canal and then ligating sac at level of pre-peritoneal fat by applying gentle traction on superficial inguinal ring . In FGH, inguinal herniotomy was performed after opening inguinal canal. Patients were discharged on same day and were called for follow up at one week to rule out any complications (secondary outcome) and six months interval post operatively to look for recurrence (primary outcome). Recurrence was labelled if there was re-appearance of reducible swelling in inguino-scrotal region assessed after six months of procedure and ultrasonography of the swelling showed abdominal contents. Doppler ultrasound and assessment of pre-operative and post-operative testicular volume was also done to rule out testicular atrophy. It was assessed by medical officer of OPD, who was blind to random assortment of patient and the type of herniotomy done.The data was collected by the researcher himself on the prescribed proforma. Data was entered and analyzed in SPSS version 23. Quantitative variables like age were presented as mean and standard deviation. Qualitative variables like recurrence were presented as frequency and percentage. Comparison of two groups’ outcome was done by applying chi-square test and p value <0.05 was taken as significant. Effect modifiers like size of defect and age of patient were stratified and post stratification comparison of two groups was done.Total patients enrolled were 260. Out of these, 158 (60.8%) patients had right sided inguinal hernia, 90 (34.6%) had left inguinal hernia, while remaining 12 (4.6%) had bilateral inguinal hernia. Mean age of patients in Group-A was 5.2±3 years while in Group-B,the mean age for children undergoing Ferguson Gross herniotomy was 5.9±3.1 years. Mean weight of children in Group-A was 17.93±6.7 kg, while the mean weight of children in Group-B was 19.1±6.98 kg. Mean operation time in Group-A was 26.65±3.22 minutes and 15.92±4.22 minutes in Group-B. Mean size of incision in Group-A was 2.5±0.11 cm and in Group-B was 2.8±0.1 cm.Eleven (8.5%) patients had tearing of processus vaginalis in MBH and only one (0.8%) in FGH. None of patients undergoing both techniques developed wound infection post-operatively. While 38 (29.2%) developed scrotal oedema in MBH and 7 (5.4%) developed it in FGH. Eight patients (6.2%) in Group-A developed scrotal hematoma, while 4 (3.1%) developed it in Group-B.Recurrence was noted in 1 (0.8%) cases in MBH while it was observed in 8 (6.2%) cases in FGH, with p value of 0.018. One (0.8%) patient who underwent FGH developed testicular atrophy and no patient had testicular retraction.There was no difference in recurrence in both groups even when compared post stratification for age and size of ring, as seen in Although inguinal herniotomy is a commonly performed procedure, yet different surgeons prefer different techniques and different approaches.In this study, 60.8% patients had right inguinal hernia while 34.6% had left inguinal hernia. Right sided inguinal hernia was found to be almost twice more common than left inguinal hernia which is very much consistent with published literature.13Operation time in Mitchell Banks herniotomy was 26.65±3.22 minutes while the mean operation time in Fergusson Gross herniotomy was 15.92±4.22 min. The increased operation time may be due to less familiarity with the procedure by all surgeons especially residents, needing supervision and a need to apply traction at times, to achieve high ligation of the hernia sac. This also contributed to more tearing of processus vaginalis in MBH (11 patients) and only 1 (0.8%) developing it in FGH. Yoshimura and colleagues have reported that operative times are more for residents performing herniotomy as compared to specialists.14More patients in MBH developed scrotal oedema and haematoma probably because of extra dissection and extra traction required in this technique. Thirty eight patients developed scrotal oedema (29.2%) in MBH while seven (5.4%) developed it in FGH. Eight patients (6.2%) developed scrotal haematoma in MBH while four (3.1%) developed in FGH. This is more than other such comparative studies such as study conducted by Turk et al in which the incidence of scrotal oedema and hematoma was 1% and 0.6% in FGH Group-And 0.7% and 0.6% respectively in MBH group.16st year of repair, with 5.1 cases reported in 10,000 persons per year.17One patient developed testicular atrophy in Group-B. The incidence reported is 2-3% after incarceration.Recurrence was less in MBH technique (0.8%). The length of inguinal canal and wider external ring are important factors for the success of MBH in children. Studies have documented the inguinal canal length in a range of 4-23mm to a maximum of 40-50mm, an average of 0.7-1.9 cm in children younger than 13 years.10Reported recurrence rate are relatively lower in uncomplicated inguinal hernia, around 1-2.5%. The most important factors contributing include adequate surgical training, experience, and tissue handling.15Recurrence was observed for only up to six months which is a brief period because recurrence has been reported even up to 6.7 years after the procedure in a recent study with a long follow-up. The reported median time was 209 days with time interval increasing with older age, although the majority of recurrences occurred within the first year following hernia repair (60%).It is short period of follow-up and conducting it in a single centre. The results may be generalized as different surgeons performed both procedures.Mitchell-Banks’ herniotomy has lower recurrence rate than Ferguson and Gross Herniotomy in boys older than two years.HMA: designed, data collection, statistical analysis, final approval and accountable for manuscriptFN: conceived, manuscript writing, final approval and accountable for manuscriptUS: data collection, reference writing, final approval and accountable for manuscriptGB: reviewed the manuscript, statistical analysis, final approval and accountable for manuscript


Human sapovirus (SaV) is an etiologic agent of acute gastroenteritis (AGE) in all age groups worldwide. Genetic recombination of SaV has been reported from many countries. So far, none of SaV recombinant strain has been reported from Thailand. This study examined the genetic recombination and genotype diversity of SaV in children hospitalized with AGE in Chiang Mai, Thailand.Stool samples were collected from children suffering from diarrhea who admitted to the hospitals in Chiang Mai, Thailand between 2010 and 2018. SaV was detected by RT-PCR and the polymerase and capsid gene sequences were analysed.From a total of 3,057 samples tested, 50 (1.6%) were positive for SaV. Among positive samples, SaV genotype GI.1 was the most predominant genotype , followed by GII.1 and GII.5 , GI.2 , GIV.1 , and GI.5 . In addition, 4 SaV recombinant strains of GII.1/GII.4 were identified in this study .The data revealed the genetic diversity of SaV circulating in children with AGE in Chiang Mai, Thailand during 2010 to 2018 and the intragenogroup SaV recombinant strains were reported for the first time in Thailand. Sapovirus of the Caliciviridae family. SaV particle is a small, non-enveloped with 30–35 nm in diameter. SaV has a positive-sense, single stranded RNA genome of about 7.1–7.7 kb in length which contains two open reading frames (ORFs) (Sapovirus (SaV) is one of the important pathogens that cause outbreaks and sporadic cases of acute gastroenteritis (AGE) in people of all ages worldwide . Prevales (ORFs) . ORF1 ens (ORFs) . Based os (ORFs) . Human Ss (ORFs)  with ones (ORFs) . Among ts (ORFs) . Like nos (ORFs) . Within s (ORFs) . Some ofs (ORFs) . In ThaiStool samples were collected from children who admitted to hospitals with AGE during the period 2010 to 2018 from five major hospitals in Chiang Mai province, northern Thailand, including Maharaj Nakorn Chiang Mai Hospital, Sriphat Medical Center, Nakornping Hospital, Sanpatong Hospital, and Rajavej Chiang Mai Hospital. The age of patients enrolled in this study ranged from neonate to 15 years old. Acute gastroenteritis was defined by watery diarrhea with three or more stool episodes per day for less than 14 days . All spehttps://www.thermofisher.com/, USA) according to the manufacturer’s instruction. SaV was screened by conventional PCR method using GoTaq DNA polymerase  with primers SLV5731 and SLV5749  using the Geneaid Viral Nucleic Acid Extraction Kit II  according to the manufacturer’s protocol. The viral RNA was reverse transcribed to cDNA using random hexamer primers and RevertAid™ reverse transcriptase  with forward and reverse primers SLV5731 and SLV5749, and analyzed by using Applied Biosystems 3100 Genetic Analyzer . Nucleotide sequences of partial capsid gene were analyzed manually using BioEdit and Clustal X softwares. Identification of virus genotype was initially determined by using the BLAST Tool (https://blast.ncbi.nlm.nih.gov/Blast.cgi) and Human Calicivirus Typing Tool (https://norovirus.ng.philab.cdc.gov/) and confirmed by phylogenetic analysis using MEGA7 software package  was used to purify amplicons of SaV-capsid gene according to the manufacturer’s protocol. All purified PCR products were direct sequenced using Applied Biosystems BigDye package . The treX86560), were analyzed. The possible recombination point of SaV strain was determined by using SimPlot software v.3.5.1 (p < 0.01)  region was amplified by using primers shown in  v.3.5.1 . In addi < 0.01) .MN245671 to MN245579 and MN253492 to MN253541 for the polymerase and capsid gene sequences, respectively.Nucleotide sequences of the polymerase and capsid regions of SaV strains detected in this study were deposited in the GenBank database under the accession numbers A total of 3,057 stool samples collected between 2010 and 2018 were screened for the presence of SaV. The average of SaV detection rate over the study period of nine years was 1.6% (50 out of 3057) . From 20The partial capsid gene sequence (308 nucleotides) of 50 SaV strains were analyzed to identify genotype of the virus. Seven different genotypes were identified in the present study: GI.1 (20), GI.2 (7), GI.5 (1), GII.1 (8), GII.4 (4), GII.5 (8), and GIV.1 (2). Phylogenetic analysis revealed that 20 SaV GI.1 strains were clustered with the GI.1 strains reported previously from USA, Korea, Japan, and Brazil  and showp = 1.572 × 10−14 and p = 1.496 × 10−12, respectively) while other 2 strains (CMH-S050-17 and CMH-S057-17) displayed the recombination point at position 5091 .In the SaV genome, recombination event typically occurs between the polymerase (RdRp) and capsid (VP1) genes. To investigate the genetic recombination of SaV strains detected in this study, we further amplified the polymerase gene of the viruses. The partial RdRp gene sequence (745 nucleotides) was successfully obtained from 49 of 50 SaV-positive samples. Phylogenetic tree of the partial RpRp region of 49 SaV strains was constructed  and the Among SaV positive cases, the highest detection rate was seen in patients with the age of 2 to <3 years (40.5%), followed by 1 to <2 years (35.7%), less than 1 year (9.5%), 3 to <4 years (7.1%), 4 to <5 years (4.8%), and more than 5 years (2.4%). In addition, this study identified 6 different genotypes and one recombinant pattern of SaV. Distribution of SaV genotypes detected in different age groups of patients is shown in Enteric caliciviruses including noroviruses and sapoviruses are the major causes of AGE of human in all age group worldwide . The detAmong different genogroups of SaV, the SaV GI (GI.1 and GI.2) and GII (GII.1 and GII.2) are the most predominant genogroups circulating worldwide while other genotypes are rarely detected in some particular countries . SimilarRNA recombination plays a key role in virus evolution and leads to its pathogenicity and virus diversity . At leasIn summary, the results of this study highlight the impact of SaV in diarrheal diseases among children in Chiang Mai, Thailand over the period of nine years and is the first report to describe recombinant SaV infection in Thai children suffering with AGE. The data of nucleotide analysis of both polymerase and capsid genes from this study provide useful information for a better understanding on the caliciviruses other than noroviruses.10.7717/peerj.8520/supp-1Supplemental Information 1Click here for additional data file.10.7717/peerj.8520/supp-2Supplemental Information 2Click here for additional data file.10.7717/peerj.8520/supp-3Supplemental Information 3Click here for additional data file.


P < 0.001). Ten patients not diagnosed with cirrhosis at enrollment but median APRI ≥ 2.0 developed HCC. Multivariate analysis showed age, gender, cirrhosis and APRI were predictors of HCC while study site and SVR were not. In this study of HCV patients, HCC incidence in the PUHSC cohort was lower than in the UMHS cohort, due to lower proportion of PUHSC patients with cirrhosis. APRI can identify risk of HCC among patients not diagnosed to have cirrhosis.Hepatitis C virus (HCV) infection is the main cause of hepatocellular carcinoma (HCC) in the United States (US) and an increasingly common cause of HCC in China. We aimed to evaluate the incidence and risk factors of HCC in HCV patients in the US and China. 795 HCV RNA + patients without HCC from University of Michigan Health System (UMHS) in the US and 854 from Peking University Health Sciences Center (PUHSC) in China were prospectively followed for a median of 3.2 and 4.0 years, respectively. 45.4% UMHS and 16.2% PUHSC patients had cirrhosis. 57.6% UMHS and 52.0% PUHSC patients achieved SVR. 45 UMHS and 13 PUHSC patients developed HCC. Cumulative incidence of HCC at 5 years was 7.6% in UMHS and 1.8% in PUHSC cohort ( The prevalence of chronic HCV infection in the United States (US) is estimated to be 1.0–2.0%, affecting between 2.7–5.2 million people3. The prevalence of chronic HCV infection in China is estimated to be 1%, with approximately 10 million persons infected4. Complications related to chronic HCV infection usually arise 3–4 decades after infection5. The US is currently experiencing a peak in HCV-related complications due to the high incidence of HCV infection in the 1970s and 1980s, and chronic HCV infection is the leading cause of HCC in the US7. In China, the majority of patients with HCV were infected more recently than in the US, predominantly in the 1980s and 1990s. Due to the late introduction of and limited access to direct-acting antivirals (DAAs) in China, complications of HCV infection, including HCC, are expected to increase8.Globally, an estimated 71 million people have chronic hepatitis C virus (HCV) infection and approximately 399 000 people die from hepatitis C each year, primarily due to complications of cirrhosis and hepatocellular carcinoma (HCC)9. Achievement of a sustained virologic response (SVR) after antiviral therapy is associated with a significant reduction in incidence of HCC; however, HCC risk is not eliminated even after SVR11.Host , virus , and environmental  factors contribute to progression of hepatitis C12. The current study utilized prospective longitudinal data in these two cohorts to compare the incidence of HCC and to study factors associated with HCC development.In 2011, we initiated a parallel cohort study of patients with chronic HCV infection in the US and in China to compare the incidence and risk factors of clinical outcomes. We previously reported that at enrollment, a significantly higher proportion of US patients had cirrhosis (38.2% vs. 16.0%) and HCC (14.1% vs. 2.7%) than the Chinese patientsA total of 1957 patients were enrolled: 1000 at UMHS, and 957 at PUHSC. Of these, 167 were excluded for having HCC (141 UMHS and 26 PUHSC) at enrollment, and 141 (64 UMHS and 77 PUHSC) were excluded due to lack of follow-up. The remaining 1649 patients: 795 at UMHS and 854 at PUHSC were included in this analysis. Figure UMHS patients were more likely to be men (57.4% vs. 48.2%), older (median age 57 vs. 53 years), obese (39.7% vs. 17.7%), and diabetic (21.3% vs. 9.5%) than PUHSC patients (Table 13 (median 2.2 vs. 0.6) and higher Fibrosis index based on 4 factors (FIB-4)14 (median 6.4 vs. 1.7) than those with no cirrhosis.The UMHS cohort included 434 (54.6%) patients without cirrhosis and 361 (45.4%) with cirrhosis of whom 87 had history of decompensation; while the PUHSC cohort included 716 (83.8%) patients without cirrhosis and 138 (16.2%) with cirrhosis of whom 38 had history of decompensation , 45 UMHS patients and 13 PUHSC patients were diagnosed with HCC. Of these, 37 (9 decompensated) UMHS and 11 (4 decompensated) PUHSC patients had cirrhosis at enrollment while 8 UMHS and 2 PUHSC patients did not meet criteria for cirrhosis at enrollment. Diagnosis of HCC was biopsy proven in 8 UMHS patients and 2 PUHSC patients, and based on imaging in the remainder.The incidence of HCC was 1.8 (95% CI 1.3–2.4) per 100 person-years in the UMHS cohort and 0.4 (95% CI 0.2–0.7) per 100 person-years in the PUHSC cohort (P < 0.001). There were no differences in incidence of HCC among the three Chinese sites: 0.7 (95% CI 0.3–1.3), 0.2 (95% CI 0.1–0.6), and 0.2 (95% CI 0.03–1.5) per 100 person-years in Beijing, Gu’an, and Kuangcheng, respectively. The cumulative incidence of HCC at 1, 3, and 5 years of follow-up was 1.5%, 4.9% and 7.6%, respectively in the UMHS cohort, and 0.4%, 1.2% and 1.8%, respectively in the PUHSC cohort (P < 0.001)  vs. 0.1 (95% CI 0.02–0.3) per 100 person-years (P = 0.01) and cumulative incidence at 5 years 2.9% (95% CI 1.5–5.4%) vs. 0.4% (95% CI 0.1–2.0%), but not in those with cirrhosis: 3.3 (95% CI 2.4–4.5) vs. 2.4 (95% CI 1.3–4.3) per 100 person-years (P = 0.44) and cumulative incidence at 5 years: 15.2% (95% CI 11.2–20.8%) vs. 10.9% (95% CI 5.9–20.0%)  UMHS patients and 444  PUHSC patients.Among patients without baseline cirrhosis, 10 patients (8 UMHS and 2 PUHSC) developed HCC before achieving SVR, while no patients developed HCC after a total of 907 person-year post-SVR follow-up  not diagnosed to have cirrhosis at enrollment developed HCC during follow-up. Median APRI at baseline was 2.0 and FIB-4 was 4.5 in these 10 patients, compared to 0.6 and 1.7, respectively in those who did not develop HCC. Of note, none of 509 patients with baseline APRI ≤ 0.5 and none of 437 patients with baseline FIB-4 < 1.45 developed HCC during follow-up, while 5 of 86 (5.8%) patients with baseline APRI > 2.0 and 8 of 161 (5.0%) with baseline FIB-4 > 3.25 developed HCC. Of the 10 patients who developed HCC, 3 met protocol criteria for cirrhosis at the time of HCC diagnosis, and an additional 3 had APRI > 2.0 and FIB-4 > 3.25 but did not meet protocol criteria for cirrhosis at the time of HCC diagnosis.Due to the small number of HCC outcome, analysis of risk factors of HCC in the group with no cirrhosis at baseline is exploratory. Multivariate analysis showed that older age, diabetes, APRI > 2.0, and decompensation during follow-up were independently associated with a higher risk of HCC, while achieving SVR was independently associated with a lower risk of HCC in the combined cohort of UMHS and PUHSC patients with no cirrhosis at baseline Fig. D.Chronic HCV infection is the leading cause of HCC in the US and an increasingly common cause of HCC in China. Our study sought to compare the incidence of HCC in UMHS and PUHSC HCV cohorts and to identify the risk factors of HCC development. We found that HCC incidence in the PUHSC cohort was lower than in the UMHS cohort, mainly due to a lower proportion of PUHSC patients with cirrhosis.16, which was confirmed in the combined cohort and UMHS cohort. Previous studies demonstrated that obesity, diabetes, alcohol or tobacco use increased risk of HCC in HCV patients20. In our study, diabetes and tobacco use were associated with a higher risk of HCC on univariate analysis but not on multivariate analysis in the combined cohort. We were not able to confirm the associations of higher BMI and alcohol use with HCC possibly due to the small number of patients with HCC.Other differences in the two cohorts may also contribute to the higher incidence of HCC in the UMHS cohort, e.g., more men, higher BMI, more diabetes and more patients with history of regular alcohol or tobacco use. Male sex had been shown in many studies to be a predictor of HCC22. Coffee consumption had been demonstrated to have a protective effect against HCC23. In our study, coffee consumption was associated with lower HCC incidence on univariate analysis but not on multivariate analysis in the combined cohort.Twenty patients in the PUHSC cohort and none in the UMHS cohort were HBsAg positive but none of them developed HCC during follow-up. There was a lower prevalence of anti-HBc and more frequent coffee consumption in the UMHS cohort. We found no difference in prevalence of anti-HBc between patients with and those without HCC development in the combined cohort and also when the two cohorts were separately analyzed. Reports on the role of anti-HBc positivity and occult HBV infection in HCC development among patients with chronic HCV infection showed conflicting results24. We found that APRI and FIB-4 can stratify the risk of HCC in patients who did not have a diagnosis of cirrhosis. Among the patients with no cirrhosis at enrollment, none of the patients with baseline APRI ≤ 0.5 or FIB-4 < 1.45 developed HCC during follow-up. Validation of our finding will help to identify HCV patients with advanced fibrosis or undiagnosed cirrhosis who might benefit from HCC surveillance.In our study, the most consistent predictor of HCC was cirrhosis. The higher proportion of UMHS patients with cirrhosis at enrollment resulted in a significantly higher incidence of HCC in the UMHS than the PUHSC cohort. When patients were stratified for cirrhosis at enrollment, there was no difference in incidence of HCC in the two cohorts among the patients with cirrhosis, overall and when stratified for presence or absence of decompensation. Among the patients with no cirrhosis, a higher incidence of HCC in the UMHS cohort persisted likely because the UMHS patients had more advanced fibrosis when compared to the PUHSC cohort (median APRI 0.62 vs. 0.53). Indeed, of the 10 patients with no cirrhosis at baseline, in whom HCC developed during follow-up, 3 met protocol criteria for cirrhosis and an additional 3 had APRI > 2.0 and FIB-4 > 3.25 at the time of HCC diagnosis, and 4 of these 6 were UMHS patients. While most HCV-related HCC develops in patients with cirrhosis, it can occur in those with advanced fibrosis25. The results of these studies can be potentially biased even when stratified for cirrhosis status at enrollment because patients with more advanced liver disease are more likely to develop HCC and at the same time less likely to achieve SVR. In a French cohort study of 1270 HCV-associated cirrhosis patients (336 treated with DAAs and 934 treated with interferon) in which SVR was used as a time-dependent variable, SVR was independently associated with a lower risk of HCC 26.Most studies showing a significant reduction in incidence of HCC after achieving SVR have used SVR as a time-fixed variableIn our study, we used SVR as a time-fixed variable as well as a time-dependent variable. Using SVR as a time-fixed variable, we found that SVR was associated with a significant reduction in incidence of HCC. When we used SVR as a time-dependent variable, SVR was not associated with a statistically significant reduction in incidence of HCC overall, possibly because of the short duration of post-SVR follow-up, median (IQR) 12.0 (4.6–19.4) months in UMHS cohort and 0 (0–22.5) months in PUHSC cohort. However, SVR was associated with a statistically significant reduction in incidence of HCC in patients with no cirrhosis and those with decompensated cirrhosis at baseline. We also found that the incidence of HCC after SVR was still high in cirrhosis patients while no HCC occurred after SVR in non-cirrhosis patients. These data highlight the importance of continued HCC surveillance in patients with cirrhosis prior to achieving SVR, and the need to diagnose and treat patients early, prior to cirrhosis.Our study has notable strengths. The parallel study design and the prospective nature of our study allow us to compare the rate of incident HCC in two cohorts of patients with chronic HCV infection in the US and in China. The use of standardized protocol, manual of procedures, and criteria for diagnosis of cirrhosis and HCC, and source documents to verify these diagnoses provide confidence in our results. There are several limitations in our study. First, while this study enrolled more than 1600 patients, the number is too small to be representative of patients with chronic HCV infection in the US and in China. Second, our follow-up duration, in particular the duration of post-SVR follow-up, was short, limiting our ability to study the impact of SVR on long-term risk of HCC. Third, the number of HCC events was small limiting the power to detect risk factors within as well as between cohorts. Fourth, there was ascertainment bias in our study because if a patient was lost to follow-up and developed HCC then we would have no way to record this HCC event.In summary, our study found that HCC incidence in the PUHSC cohort was significantly lower than in the UMHS cohort. This difference is mainly due to less advanced liver disease in the PUHSC cohort. Incidence of HCC was decreased but not eliminated in cirrhosis patients who achieved SVR. By contrast, no HCC was observed in non-cirrhosis patients who achieved SVR. Among patients with no cirrhosis, high APRI identified those who were at risk of HCC. Our data support that patients with chronic HCV infection should be treated prior to development of cirrhosis to prevent liver-related complications, including HCC.12. In brief, consecutive adults age ≥ 18 years with chronic HCV infection (HCV RNA positive) were enrolled between September 2011 and July 2015. Patients who had undergone liver transplantation, known coinfection with HIV, life expectancy < 12 months due to extra-hepatic illnesses, or were receiving HCV treatment at enrollment, were excluded. Patients enrolled at both centers were evaluated using an identical protocol. All patients except those with HCC at enrollment were prospectively followed. Patients with cirrhosis were evaluated every 6 months while those without cirrhosis were evaluated every 12 months. Follow-up continued until patient died, developed HCC, received liver transplantation, withdrew informed consent, or when the study was closed in December 2017. Patients who did not have any follow-up visit after enrollment were excluded from this analysis. The research protocol was approved by the Institutional Review Boards of both the University of Michigan and Peking University Health Science Center and conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all subjects.We conducted a prospective study of two parallel cohorts of patients with chronic HCV infection recruited in Ann Arbor, US  and in Beijing, China . Patients in China were enrolled from three sites: Peking University People’s Hospital in Beijing, and Gu’an and Kuancheng clinics in Hebei. A description of the study design had been previously reportedProtocol, surveys, and data forms were developed in English and then translated into Chinese, and data were entered into a web-based database.Demographic , clinical , and laboratory data , abdominal imaging , liver elastography and liver histology results were collected at baseline and at each follow-up visit.Alcohol, tobacco and coffee consumption were assessed using a standardized questionnaire. Regular alcohol use was defined as at least 1 drink/day, regular tobacco use was at least one cigarette/day, and regular coffee consumption at least 1 cup/day.227. For Chinese patients, overweight was defined as BMI ≥ 24 but < 28, and obesity as BMI ≥ 28 kg/m228. Diabetes mellitus (DM) was defined by medical history or use of medications for treatment of diabetes; and for those with no history of diabetes by fasting blood glucose ≥ 126 mg/dL or random blood glucose ≥ 200 mg/dL.For American patients, overweight was defined as body mass index (BMI) ≥ 25 but < 30, and obesity as BMI ≥ 30 kg/m9/L in the absence of other explanations, liver stiffness measurement by vibration controlled transient elastography (Fibroscan) > 13 kPa, and gastro-esophageal varices on endoscopy. HCC was diagnosed by histology or by triple phase CT or MRI per the American Association for the Study of Liver Diseases guidelines29. Source documents supporting the diagnosis of cirrhosis and HCC were collected and investigators from each country audited the documents from the other country to confirm these diagnoses.Diagnosis of cirrhosis was based on histology when available. In the absence of histology, diagnosis of cirrhosis was based on evidence of clinical decompensation or 2 of the following 4 criteria: radiological imaging showing features of cirrhosis , platelet count < 100 × 10Data were analyzed using SAS 9.4 . Categorical data are presented as number (percent) and continuous data as median . T-test or Mann–Whitney test was used to compare continuous variables according to the data distribution and chi-square test for comparison of categorical data. Kaplan–Meier analysis was used to estimate cumulative incidence of HCC. Univariate and multivariate competing risk models were used to identify risk factors of HCC. Death or liver transplantation before HCC diagnosis was considered as competing risk event, and SVR was included as a time-dependent variable. Due to the short duration of post-SVR follow-up, analysis was also performed with SVR as time-fixed variable. Demographic, clinical and environmental factors with P < 0.1 on univariate analysis were incorporated in the full model. P values < 0.05 were considered statistically significant.Supplementary Figure 1.Supplementary Figure 2.Supplementary Information 3.


To determine the diagnostic potential of prevertebral soft-tissue (PVST) swelling in cervical spine ligamentous injury (LI).PVST swelling in the cervical spine is a historical indicator of cervical spine injury; however, at present, there are no limited objective criteria to use PVST swelling to guide clinical decision-making regarding cervical spine LI. This study investigates PVST thickness as a screening measure for cervical spine LI with a potential to identify indications for advanced imaging.The registry at an urban level 1 trauma center was queried for cervical spine injuries between 2010 and 2016. Twenty-nine patients with LIs who had both CT and MRI available were included. Fifty-nine patients with bony injury (BI) were also included, and 99 patients undergoing CT of the cervical spine after blunt trauma without evidence of cervical spine injury were included as control patients.P < 0.01). 86.2% of patients with LI (25 of 29) had associated BI. Patients who had LI and no associated BI (n = 4) were all men, and all had PVST thickness >11.5 mm at C7 (avg. PVST 17.7 mm ± 2.5).PVST swelling >11.5 mm at C7 was 89.7% sensitive (72.7% to 97.8%) and 51.5% specific (41.3% to 61.7%) for LI. In men, a PVST thickness of 11.5 mm at C7 was 96% sensitive (79.7% to 99.9%) and 46.2% specific (32.2% to 60.5%) for LI. Patients with LI were more likely to be men (86.2% versus 52.5% control, C7 PVST thickness >11.5 mm was highly sensitive but poorly specific for cervical spine LI. This threshold may represent an appropriate PVST thickness to rule out LI because patients with PVST ≤11.5 mm are unlikely to have cervical spine LI and may not benefit from MRI. Although uncommon, injuries isolated to these structures can be unstable and can result in substantial neurologic deficit.5 The question of whether to supplement a negative CT scan with more advanced imaging, such as MRI, is currently a subject of debate. MRI is more costly than CT, and in an increasingly restricted payer environment, establishing the appropriate criteria for use remains especially relevant. Any failures to identify unstable cervical spine discoligamentous injuries (LIs) in setting of a negative CT scan may result in disastrous outcomes for the patient.The clinical criteria for identifying an uninjured cervical spine in patients who are awake and alert without distracting injury, neurologic deficit, intact range of motion, or cervicalgia is well established and highly sensitive.4 In contrast to this recommendation, other authors have shown MRI to change the management in certain patients with negative admission CT by means of surgical intervention and/or continuation of cervical collar.6-8 Thus, it would be of value to determine which patients with negative admission CT would benefit from further evaluation with MRI. Ideally, a set of objective indicators of occult cervical spine injury on CT would be established. Some authors have already reported the retrospective finding of subtle CT signs of disco-LI after injuries were diagnosed acutely via MRI.7-9The most recent Eastern Association for Surgical Trauma guideline for cervical spine clearance in the unreliable patient conditionally recommends the removal of cervical collar after negative high-quality CT; a recommendation based on the strong negative predictive value of CT in excluding critically unstable injuries to the cervical spine, although the guidelines acknowledge that this recommendation is based only on low-quality evidence.1011121314151617 with recent studies describing various normal values for PVST on CT imaging.19 On lateral cervical radiographs, a PVST thickness of greater than 6 mm at C2 or 22 mm at C6 was traditionally thought to indicate cervical spine injury. However, these values were shown to be more specific rather than sensitive for cervical spine injury and were not recommended as a screening tool because it is critical to establish a threshold that limits false negatives.16 A recent study examined the PVST thickness on CT and showed that the cutoff for injury of 1 to 2 SDs above the normal at C2 and C6 was a highly specific, yet poorly sensitive measure of occult cervical spine injury.18 No recent literature has examined the potential of lower thresholds of PVST thickness for injury; to the authors' knowledge, no study has ever examined PVST in the setting of cervical spine LI.Prevertebral soft-tissue (PVST) swelling has been classically used as an indicator of occult injury on cervical radiographs,In the present study, we aim to examine the potential of PVST in all cervical vertebral levels and various PVST thicknesses as indicators of injury. It is our hypothesis that the measurement of PVST will prove to be a valuable and objective adjunct to the interpretation of a screening CT in cervical trauma and will help inform clinicians on which patients would or would not benefit from further imaging, such as MRI, for evaluation of cervical disco-LI.20 A consecutive series of 32 patients who underwent MRI in addition to CT for cervical spine injury and were found to have LI were identified from the practice of a single, fellowship-trained spine surgeon. Patients were excluded if CT was performed at outside hospital (n = 3) where image quality and resolution could not be verified. Twenty-nine patients with LI remained and were included in the primary analysis.After institutional review board approval, the electronic medical record at an urban level 1 trauma center was queried for cervical spine injuries between 2010 and 2016 to identify a cohort of individuals with traumatic cervical spine LIs. The presence of LI and the level of injury were determined based on final radiologist read of the MRI scan.21 To determine the appropriate number of patients with BIs to serve as a comparison to those with LIs, an a priori power analysis was conducted: assuming a significance of 0.05, power of 0.80, and effect size of 0.15 resulted in an estimated sample of 59 patients with BI. Thus, 86 patients over the same period were identified who underwent CT but not MRI for traumatic cervical spine injury. Patients who arrived intubated (n = 8), underwent initial CT at outside hospital (n = 12), had subacute presentations (n = 2), had nontraumatic mechanism of injury (n = 2), had previous spine instrumentation (n = 2), or had ankylosing spondylitis (n = 1) were excluded. In total, 59 patients with BIs and no LIs were included as a comparison group.To serve as a comparison, a second consecutive series of individuals with BI and no LI were established from the same clinical practice. BI was defined as a fracture on CT scan as documented in final radiologist read.Finally, a control group of patients with no cervical spine injuries was established. An identical a priori power analysis was conducted, which revealed an estimated minimum sample size of 46 patients. Ninety-nine patients who underwent cervical spine CT but not MRI for traumatic indication were identified and were found, via a comprehensive clinical and radiographic assessment, to have no clinically evident injuries. These patients were included as uninjured control patients.19 Midsagittal planes were determined using direct axial image correlation. Measurements were taken from the midanterior portion of the vertebral body to the closest point in the air column in a plane approximately parallel to the vertebral end plates  to correct for the smaller sample size of the ligamentous and BI groups. To generate the diagnostic value of PVST at each level, the likelihood ratios were generated to predict the amount of PVST for LI. Receiver operating curves were calculated via event probabilities for each patient's C7 PVST in relation to their injury status. Event probabilities were generated via binary logistic regression between C7 PVST thickness and the presence of LI. Significance was set at P ≤ 0.05.All statistical analyses were performed with Minitab 17 (Minitab). Categorical variables were compared with the Fisher exact test, and continuous variables with Student P = 0.03) than control patients. Patients with LI were more likely to be men than control patients . No significant difference was observed in the body mass index between LI, BI, or control patients. 86.2% of patients with LI (25 of 29) also had associated BI. 93.1% of patients with LI underwent stabilization of their injuries, whereas 54.2% of patients with BI underwent surgical intervention  and 51.5% specific (41.3% to 61.7%) for LI, with a positive likelihood ratio of 1.85 (1.46 to 2.35) and a negative likelihood ratio of 0.2 (0.07 to 0.60). In men only, a PVST thickness of 11.5 mm at C7 was 96% sensitive (79.7% to 99.9%) and 46.2% specific (32.2% to 60.5%) for LI, with a positive likelihood ratio of 1.82 (1.39 to 2.37) and a negative likelihood ratio of 0.08 (0.01 to 0.59). Patients who had LI and no associated BI (n = 4) were all men, and all had PVST thickness >11.5 mm at C7 (avg. PVST 17.7 ± 2.5). PVST thickness >17.5 mm at C7 was 31.0% sensitive (15.3% to 50.8%) and 96.0% specific (90% to 98.9%) for LI in all patients, with a positive likelihood ratio of 7.68 (2.55 to 23.14) and a negative likelihood radio of 0.72 (0.59 to 0.92). In men only patients, PVST thickness >17.5 mm was 32% sensitive (14.9% to 53.5%) and 96% specific (87% to 99.5%) for LI, with a positive likelihood ratio of 8.48 (1.94 to 37.06) and a negative likelihood ratio of 0.71 (0.54 to 0.93)  the injuries studied, (2) the cutoff for injury, and (3) the vertebral level.The evaluation of PVST thickness as an indirect marker of cervical spine LI after blunt trauma is important and has the potential to expedite spine care and the trauma evaluation of these critically injured patients. In the present study, we found PVST thickness >11.5 mm at C7 to be highly sensitive but poorly specific for LI, with greatest sensitivity among male patients Table . This eqP < 0.01). Among these patients, three had disk space abnormalities prompting MRI and one underwent MRI because of neurologic change. The latter patient had a stable injury and did not require surgery. Because isolated LI can still be unstable,23 it is important for these injuries to be identified promptly because they are more likely to be missed than other forms of spine trauma and can lead to catastrophic consequences. Thus, it is especially relevant to establish updated, appropriate PVST screening criteria using modern CT scan technologies.To the authors' knowledge, no previous studies of this subject have examined PVST thickness in LI. Because LIs are soft-tissue injuries, they may have greater propensity to present with increased soft-tissue swelling as compared to isolated BI. This is supported by the stepwise increase in mean PVST seen at C7 among control, BI, and LI patients Table . AlthougThe traditional thresholds for lateral radiographs of the cervical spine of 6 mm at C2 and 22 mm at C6 are highly specific, and recent studies of PVST on CT using similarly large thresholds affirmed that these cutoffs of injury were very specific Table . In the 19 This result is encouraging because consistency in baseline PVST measurement at C7 supports its potential utility as a diagnostic tool. Although PVST at C7 has important diagnostic utility, PVST at other levels was less useful. We suspect this is because of a multitude of factors. With increased PVST at baseline, small changes will be easier to identify (larger delta). As a more cephalad location, gravity may bring more fluid in this direction. This is also a more common location for injury.5The measurements reported in this study are similar to the literature standard. The internal validity of our study was consistent with excellent degrees of inter observer and intraobserver variability at C2, C6, and C7. The novel application of such at each level should give providers more confidence in interpreting their meaning. When comparing our control patients' mean PVST thickness to previously published normal values of PVST measured on CT, there was close agreement. A comparison with published normal values for PVST measured by CT demonstrated agreement within one SD at C2, C3, and C6, although these levels were statistically significantly different between studies. Alternatively, no statistically significant difference was observed at C7 (11.5 ± 3.1 mm versus 11.6 ± 3.2 mm).18 This agreement supports the external validity of our study methodology and highlights the importance of PVST cutoff for injury and specific vertebral level measured  and could theoretically eliminate the need for MRI for the purposes of evaluating LI in one half of the patients with negative CT. For patients with C7 PVST from 11.5 to 17.5 mm, our study data were not capable of differentiating injured from control patients and clinicians should rely on existing protocols for clearing the cervical spine. Finally, C7 PVST of >17.5 mm had high specificity (96%) for LI, but only moderate positive predictive value for having a LI (59%), given the relatively low incidence of LIs.


To compare oral Nifidepine and IV labetalol in terms of rapidity of BP control in severe preeclampsia.All patients coming to Services Hospital from March 2017 to February 2019 with diagnosis of severe preeclampsia ≥ 24 weeks gestation were randomized to either receive Nifidepine or Labetalol. Primary outcome measure was time taken to control BP and number of doses required. Secondary outcome measures were side effects of drugs, APGAR score, NICU admission and perinatal mortality.Two hundred four patients were included in trial with 102 patients in each group. Labetalol took 22.6± 13.5minutes and Nifidepine took 22.09± 11.7 minutes to achieve target BP (p>0.05). Labetalol required 2.3± 1.58 doses and Nifidepine 2.2± 1.58 doses to control BP ( p>0.05). No maternal side effects were seen in 86 (84.31%) and 92(90.19%) patients in both groups (p>0.05). Mean gestational age at birth was 34.8 ±2.73weeks in Labetalol and 35.2±2.48 weeks in Nifidepine group (p>0.05). In labetalol group, 43 (42.15%) babies had APGAR Score < 7/10 and 23(22.54%) babies required admission to NICU while in Nifidepine group 42 (41.17%) babies had Apgar score < 7/10 & 30(29.4%) babies were admitted to NICU(p>0.05). There were 21(20.5%) perinatal deaths in labetalol Group-And 19(18.6%) in Nifidepine group (p>0.05)Oral Nifidepine and IV labetalol are equally efficacious in controlling BP in patients with severe pre eclampsia without any significant side effects. Hypertensive disorders of pregnancy complicate 4-7% of pregnancies and the second leading cause of maternal death worldwide2The only effective treatment of severe preeclampsia is delivery of the fetus but immediate antihypertensive treatment is given to stabilize the patient and prevent further complications. Intravenous drugs in the form of labetalol and hydralazine have been traditionally used as first line drugs for control of severe hypertension in pregnancy. Although adverse effects of drugs have been reported but both are effective in controlling BP in severe pre eclampsia. Nifidepine is a calcium channel blocker with advantages of oral administration. Worldwide trials comparing Nifidepine, hydralazine and labetalol in hypertensive emergency have been conducted with variable results regarding their efficacy in controlling BP and fetal effects.8Pakistan has high burden of hypertensive disease in pregnancy. Eclampsia is second major cause of maternal death and claims 2000 maternal lives per year.This open label randomized control study was conducted in the Department of Obstetrics & Gynecology, Services Institute of Medical Sciences, Services Hospital Lahore from March 2017 to February 2019. Services Hospital Lahore is a tertiary care hospital attached to public sector medical college, catering the needs of a large population. Ethical approval for the study was taken by the Institutional Review Board (IRB) SIMS, Services Hospital Lahore on February 16, 2017 number IRB/2017/306/SIMS and Trial Registration no: NCT03325348.All pregnant patients’ ≥28 weeks of gestation diagnosed with severe pre eclampsia as defined by systolic BP of ≥160mmHg or diastolic BP of ≥110mmHg with proteinuria and alive baby were admitted and offered to enrol in the trial after written informed consent. Women with history of chronic hypertension without proteinuria, with heart rhythm abnormalities, asthma, anomalous baby and intrauterine death were excluded from the trial. Detailed history regarding booking, drugs for hypertension, symptoms of headache, blurring of vision, dizziness and epigastric pain was taken. Their relevant investigations of blood group, complete blood count, urine complete examination, serum uric acid, liver function tests, clotting profile were sent. Ultrasound was done to see fetal wellbeing and biometry along with liquor volume. The patients were randomized to two groups based on computer generated random numbers, 102 patients in each Group-After sample size calculation. The patients in Group-A were given intravenous labetalol injection  and a mint tablet every 15 minutes. Patients in Group-B were given Nifidepine  and intravenous placebo saline injection. BP was recorded every 15 minutes until the target blood pressure of ≤150/100mmHg was achieved. Fetal heart rate monitoring was done every 15 minutes throughout administration. If BP was not controlled in one hour, other antihypertensive drugs were given. Similarly, after successful BP control, routine antihypertensive therapy was started two hours after last study drug administration. Corticosteroid injection were given for lung maturity to all participants less than 36 weeks duration. Depending on fetus and maternal condition, delivery was planned according to gestational age and bishop score.Primary outcome measure was time taken to control the BP and number of doses of drugs required. Secondary outcome measure were maternal complications of placental abruption, HELLP and eclampsia. Neonatal outcome was measured in form of Apgar score at five minutes, admission to NICU and perinatal death. Side effects of both drugs were also noted. Data was entered and analyzed using SPSS version 23. The comparison between qualitative variables was done by using chi square test or fisher Exact test where appropriate. All P-values were two tailed and p-value of 0.05 or less was considered significant.Sample size was calculated by using WHO statistical software (S.size). Assumption for sample size estimation was the hypothesis test for difference of two proportions (two sided test). The estimated sample size is sufficient to detect the difference of 20% among the two groups at significance level 5% and power of study 90%. The estimated sample size was 102 for each group.Total 204 patients were recruited in this randomized controlled study. Group-A with 102 patients was given IV labetalol and Group-B with 102 patients was given oral Nifidepine. Patient characteristics are shown in Regarding primary outcome of the study, that is time taken to achieve blood pressure control as shown in Mean gestational age at birth was 34.8±2.73 weeks in Group-A and 35.2±2.48 weeks in Group-B (p=0.292) with mean birth weight of babies 2.2±0.41 kg and 2.3±0.38 kg respectively in Group-A and B. In Labetalol Group, 43 (42.15%) babies had APGAR Score < 7/10 and 23(22.54%) babies required admission to NICU. In Nifidepine group 42 (41.17%) babies had Apgar score < 7/10 & 30(29.4%) babies were admitted to NICU (p>0.05). There were 81 (79.5%) live births, 3 (2.9%) still births & 18(17.6%) early neonatal deaths while in Nifidepine group, there were 83 (81.3%) live births, 5(4.9%) still births & 14 (13.7%) neonatal deaths (p=0.328).Mean age of our patients was comparable in both groups (28.1±4.37 years and 24.6±4.65 years (p>0.05). 69.6% and 60.7% patients in both groups were primigravida, as is the case worldwide that majority are primigravida.7In our study, labetalol and Nifidepine were found to be equally effective in controlling BP in pregnant women with severe preeclampsia taking mean time of 22.69±13.5 and 22.09±11.7 minutes each(p>0.05). Number of doses required were not statistically different in both groups as mean dose to control BP was 2.36±1.5 doses in labetalol Group-And 2.28±1.58 doses in Nifidepine group(p>0.05). Similar trials conducted by Raheem et al, Shekhar et al, Anjuman et al and Yogita et al showed that BP control was controlled significantly earlier in patients who were given Nifedipine as compared to labetalol and they required less number of doses.The side effects profile of the patients was comparable and 84.3% patients of labetalol Group-And 90.1% patients in Nifidepine group did not experience any side effects(p>0.05). Only few experienced palpitations, headache and hypotension which was well tolerated. Another study from Lahore comparing Nifidepine to hydralazine has also shown minimal side effects with nifedipine.16In this study, average gestation was 34.8±2.73 weeks in labetalol Group-And 35.2±2.48 weeks in patients given Nifidepine with average birth weight of 2.2±0.41kg and 2.3±0.38 kg respectively (p>0.05) This is in contrast to studies reported by Raheem et al and Yogita et al where majority babies delivered at gestational age of 37-39 weeks.APGAR score<7 at five minutes was seen in 43.15% and 41.17% patients in labetalol and Nifidepine groups respectively. Although more patients (29.4%) on Nifidepine required NICU admissions as compared to 22.5% patients in labetalol Group-But it was not statistically significant(p>0.05). Li QQ in meta-analysis reported better BP control with Nifidepine but no difference in APGAR score and perinatal outcome.Prematurity and growth restriction have a major role in adverse perinatal outcome in this study. NICU in government hospitals is overburdened with overwhelming number of patients and poor resources lead to increased chances of early neonatal death in premature babies. Increasing burden of perinatal mortality for severe hypertension is reported from other developing countries as well.19Oral Nifidepine and IV labetalol are equally efficacious in controlling BP in patients with severe pre eclampsia without any significant side effects. Neonatal outcome in terms of NICU admission and perinatal mortality is also comparable. Nifidepine can be recommended as first line drug for control of severe hypertension due to ease of oral administration, cost effectiveness and easy availability.TW: Conceptualized and designed the study, reviewed the manuscript and approved the final version. She is responsible for accuracy and integrity of work.SA: contributed to maintenance of data base and initial writing of script.KS & AR: did the data entry and statistical analysis.


Malaria is one of the main causes of death in Angola, particularly among children under 5 years of age. An essential means to improve the situation is with strong malaria case management; this includes diagnosing suspected patients with a confirmatory test, either with a rapid diagnostic test (RDT) or microscopy, prompt and correct treatment with artemisinin-based combination therapy (ACT), and proper case registration (track). In 2011, the United States President’s Malaria Initiative (PMI) launched a country-wide programme to improve malaria case management through the provision of regular training and supervision at different levels of health care provision. An evaluation of malaria testing, treatment and registration practices in eight provinces, and at health facilities of various capacities, across Angola was conducted to assess progress of the national programme implementation.χ2) tests were used to identify factors associated with “knowledge”, “test”, “treat” and “track.” Multivariable logistic regression models were used to assess factors associated with the defined outcomes.A retrospective assessment analysed data collected during supervision visits to health facilities conducted between 2012 and 2016 in 8 provinces in Angola. The supervision tool used data collected for malaria knowledge, testing, treatment and case registration practices among health workers as well as health facilities stock outs from different levels of health care delivery. Contingency tables with Pearson chi-squared (p < 0.01), 7.4 (95% CI: 6.1–9.0) times as likely to test more suspected cases (p < 0.01), 10.9 (95% CI: 8.6–13.6) times as likely to treat more confirmed cases (p < 0.01) and 3.7 (95% CI: 3.2–4.4) times as likely to report more accurately in the same period (p < 0.01).A total of 7156 supervisions were conducted between September 2012 and July 2016. The overall knowledge, testing, treatment and tracking practices among health care workers (HCWs) increased significantly from 2013 to 2016. Health care workers in 2016 were 3.3 times (95% CI: 2.7–3.9) as likely to have a higher knowledge about malaria case management as in 2013 (Improvements demonstrated in knowledge about malaria case management, testing with RDT and treatment with artemisinin-based combinations among HCWs is likely associated with malaria case management trainings and supportive supervisions. Gaps in testing and treatment practices are associated with RDT and ACT medicines stock outs in health facilities. Tracking of malaria cases still poses a major challenge, despite training and supervision. Hospitals consistently performed better compared to other health facilities against all parameters assessed; likely due to a better profile of HCWs.Significant progress in malaria case management in eight provinces Angola was achieved in the period of 2013–2016. Continued training and supportive supervision is essential to sustain gains and close existing gaps in malaria case management and reporting in Angola. Despite significant progress in the past 2 decades, Africa still accounts for 90% of malaria deaths worldwide with higher incidence in children less than five years of age . TogetheT3: Test. Treat. Track. initiative to ensure all suspected malaria cases were properly tested, treated and registered  and Uíge 29.9% (95% CI: 27.4–32.4) showing the lowest proportions, whereas Zaire [82.1% (95% CI: 79.3–84.6) and Huambo 78.0% (95% CI: 75.0–80.9)] showed the highest. Multivariate analysis showed that HWs in Zaire had 16.0 (95% CI: 12.4–20.7) times the odds of having higher knowledge than workers in Kwanza Sul (p < 0.01).Healthcare workers based in the Hospitals had a higher overall level of knowledge when compared with the ones working in the health posts [70.3% (95% CI: 63.8–76.2) vs 52.9% (95% CI: 51.6–54.3)]. In fact, Hospital based HCWs had 1.6 (95% CI: 1.2–2.2) times the odds of having a higher knowledge than workers in health posts after controlling for confounding (p < 0.01).The proportion of health facilities testing by RDT 75% or more of malaria suspected cases increased significantly over the time of the analysis from 46.9% (95% CI: 44.2–49.6) in 2013 to 82.2% (95% CI: 80.3–83.9) in 2016 (Table p < 0.01).There was a significant difference when looking at the testing practices across the different provinces, with Kwanza Sul [53.2% (95% CI: 49.3–57.1)] and Uíge [45.7% (95% CI: 43.0–48.4)] showing the lowest proportions, whereas Kwanza Norte (84.0% (95% CI: 81.5–86.4) showed the highest. Multivariate analysis showed that HFs in Kwanza Norte had 10.1 (95% CI: 7.9–12.8) times to the odds of testing more suspected malaria cases than HCWs in Uige (p < 0.01).The proportion of tested malaria suspected cases was higher in Hospitals than in health posts (80.2% (95% CI: 74.3–85.2) vs 65.9% (95% CI: 64.7–67.358.8). In fact, suspected malaria cases in Hospitals were 1.8 (95% CI: 1.2–2.7) times more likely to be test than in health posts (p < 0.01). This trend was visible throughout the program implementation period where HFs were consistently testing a higher proportion of malaria suspected cases .The proportion of health facilities treating 75% or more malaria confirmed cases with recommended artemisinin-based combinations increased significantly throughout the time of the analysis from 65.5% (95% CI: 62.8–68.0) in 2013 to 90.2% (95% CI: 88.8–91.6) in 2016 Table . Multivap < 0.01).Differences in treatment practices varied across provinces, with Kwanza Sul [66.7% (95% CI: 62.9–70.3)] and Uíge [62.6% (95% CI: 59.9–65.2)] showing the lowest proportions, whereas Benguela [96.2% (95% CI: 95.0–97.2)] and Kwanza Norte [93.1% (95% CI: 91.3–94.7)] showed the highest. Multivariate analysis showed that HFs in Benguela were 15.4 (95% CI: 10.8–21.0) times more likely to treat confirmed malaria cases with appropriate ACT medicines as HCWs in Huila  vs 78.1% (95% CI: 77.0–79.2)]. However, these differences were not statistically significant when using multivariate analysis.p < 0.01). As it is visible in Fig. The existence of ACT medicines in stock is associated with HF capacity to treat the majority of confirmed malaria cases with adequate ACT , it is possible to observe that reporting accuracy improvements throughout time were consistently lower than the other indicators measured  of reports matching the Health Facility patient registers in 2013 to 55.3% (95% CI: 53.0–57.6) in 2016 (Table p < 0.01).The lowest malaria reporting accuracy rates were registered in Kwanza Sul [25.2% (95% CI: 21.9–28.7)], whereas Huambo [83.5% (95% CI: 80.7–86.0)] showed the highest. The proportion of reports which data was matching health facility patient registers was higher in Hospitals than in health posts [51.4% (95% CI: 44.6–58.1) vs 49.7% (95% CI: 48.3–51.0)], but these differences were not found to be statistically significant. Similar proportions for the track indicator was registered between health centers and health posts. However, in multivariate analysis, health centres seemed to be less likely to report data accurately than health posts  in 2013 to 70.1% 95% CI: 68.1–72.0) in 2015 followed by a considerable fall to 64.7% (95%CI: 62.4–72.0) in 2016 (Table 8.1–72.0 Kwanza Sul [41.9% (95% CI: 38.1–45.8)] and Uige [51.1% (95% CI: 48.4–53.9)] registered the lowest proportion of HF with stocks of both ACT medicines and RDT, whereas Kwanza Norte [72.1% (95% CI: 69.1–75.0)] showed the highest. ACT medicines and RDT stocks were frequently more available in hospitals than in health care posts and health centres .Testing, treatment and tracking of malaria cases constitute the three fundamental pillars of the existing global malaria policy and strategy . This stKnowledge is a critical component in the continuum of effective malaria case prevention and management. It ensures HCWs to have the right skills to apply appropriate behaviour and practices to manage malaria cases effectively –6. The rAlthough this assessment did not explore any association between individual HCW’s knowledge and malaria training, there is evidence to support the association between improved knowledge and training , 15, 26.The results demonstrate that HCWs in Huambo were more knowledgeable than their peers in Uige. Knowledge discrepancies among HCWs between provinces are difficult to interpret, since this assessment did not explore the individual characteristics of the HCWs. However, knowledge differences among HCWs in Huambo and Zaire compared to peers in Uige and Kwanza Sul provinces, can be attributed to cumulative benefits of PMI’s malaria control interventions in Huambo and Zaire provinces, which began in 2005, compared to Uige and Kwanza Sul which were only initiated in 2011 . InteresThe results observed 2 critical findings. The 2 important components in the continuum of malaria case management and the 3 T policy—testing suspected malaria case with RDTs and treating confirmed cases with approved ACT medicines—improved significantly overtime among HCWs.In the absence of any other malaria case management quality improvement interventions, within the context of this programme, one can infer that cumulative benefits of training and supervision can affect these results. Also, it should not be excluded that experience gained by HCW over time may have played a significant role in the improvements noted. Importantly the results demonstrate a steady increase in the proportion of health facilities that test and treat over 75% of malaria cases over time as training and supervision visits were implemented. These findings are consistent with previous research that found an association between training and supervision and improved testing and treatment practices –26, 34.Although hospitals tested and treated a significantly higher proportion of malaria cases, compared to other health facilities, improvements in health posts are noteworthy, because health posts constitute approximately 70% of all health facilities, and tend to serve rural populations, which carry the highest burden of malaria . Any impAdditionally, the results demonstrate that hospitals suffered less stock-outs of RDTs and ACT medicines compared to other health facilities and, therefore, HCWs in hospitals are likely to test and treat more malaria cases , 36. DesTargeted investments to strengthen malaria commodity supply chain systems at national, provincial, municipal and health facility levels were undertaken during this period that should likely have had a bearing on the effectiveness of malaria commodity supply chain systems . These fThe variations in testing and treatment rates between HCWs in different provinces are difficult to establish, especially when assessed against similar malaria transmission epidemiological profiles, trainings and supervisions. Stark differences between the general quality of health care services between Uige and Luanda provinces may be attributed to historical, social, cultural and economic factors . The genThese findings highlight the importance of sustaining efforts in training and supervision for correct malaria diagnosis and treatment. It is essential to ensure HCW have access to adequate training that focus on major RDT misperceptions and understand the value that RDT results bring to inform the diagnosis. Overcoming most common wrong perceptions and attitudes on malaria case management is essential . HoweverMalaria data is critical to accurately measure the effectiveness of interventions against malaria and increasingly assess value for money, especially now that resources for malaria are progressively decreasing . As primWith only 55% of malaria reports correct in 2016, these results indicate that training and supervision of HCWs alone does not necessarily improve the correctness of malaria data across all categories of health facilities. Since these 2 interventions constitute the main components of quality improvement interventions for malaria control programs, more comprehensive assessments to explore factors that affect and determine malaria data quality are critical, to enable the design of more evidence-based interventions.The study did not draw comparisons with a control group of provinces in Angola with similar malaria epidemiological profiles that never benefited from the malaria control initiative. Although that was not the scope of this assessment, a comparison would have strengthened the power and generalizability of the findings, and informed on-going policy discussions aimed at extending and broadening the scope of this programme in selected provinces over the next five years. Since data was not collected in Huambo in 2016, temporal comparisons are naturally affected by this limitation.Secondly, data collection was designed to answer programmatic needs. These proved to be a limitation in commuting some variables into values that would be more appropriate to conduct further data analysis. The non-inclusion of information on number of supervision and trained health staff into data analysis is a major limitation that undermined the possibility to measure the real impact of these activities in the results found.Potential bias in data collection introduced by different supervisors in different provinces may have existed. To overcome this problem, a rigorous system of supervisor’s evaluation was put in place to ensure all complied with data collection guidelines. These monitoring visits were conducted annually to ensure regular follow up and evaluation of procedures. A potential Hawthorne effect may have happened as supervision visits were planned in advance and health workers had time to prepare for the supervision. Results reading should consider this potential source of bias. However, findings still point out several gaps in the system. Therefore, this bias may be only underestimating the potential gaps still existing in the system.Significant improvements in the quality of uncomplicated malaria case management were observed, particularly related to testing and treatment of malaria cases at all levels of health care delivery. Tracking of malaria cases continues to pose a challenge, despite on-going efforts to improve malaria data quality. The improvements registered in knowledge about malaria in this assessment seemed to have translated into better testing and treatment practices among HCWs.Hospitals continue to perform better in all parameters compared to other health facilities, and more efforts are required to bridge this gap. To sustain the gains attained within this initiative, and to improve coverage, intervention programmes must adopt a health system approach towards resolving barriers that hamper optimal coverage. Research and regular assessments must accompany programme implementation to gather more evidence and provide adequate guidance.Additional file 1. Indicators collected during formative supervision visits.


Rectovaginal area of pregnant women can be colonized transiently with group B Streptococcus (GBS) without causing disease. The bacteria can be transmitted to the newborn before and during birth and cause early-onset neonatal disease. In this study, we aimed to determine the GBS colonization rate among pregnant women before delivery and their newborns and serotypes distribution of GBS. Two hundred-eighty pregnant women along with their newborns were screened for GBS colonization from June 2014 to October 2014 at Adama Hospital Medical College. Rectovaginal swabs from pregnant women before delivery and specimen from nasal area, external ear, umbilical cord and throat of newborns were collected and cultured. The serotyping of GBS was performed by using serotype-specific antisera. To collect sociodemographic and clinical data we employed a structured questionnaire. GBS colonization among pregnant women and their newborns were 13.2% 95% CI (8.9–17.5) and 7.4% 95% CI (4.6–10.6). Out of 37 GBS strains recovered from pregnant women, the prevalent serotypes were Ia 6(16.2%), Ib 8(21.6%), II 10(27%), III 3(8.1%), and V 8(21.6%). Out of 21 GBS strains recovered from newborns, prevalent serotypes were Ia 3(14.3%), Ib 6(28.6%), II 6(28.6%), III 4(19%), and V 1(4.8%). This study indicated the existence of primary risk factors for neonatal disease in Adama area. Serotype II was the common serotype detected in this study which is followed by serotype Ib, Ia, and V. As colonizing GBS serotypes could cause invasive disease among newborns, vaccine formulation which includes serotype II, Ia, V, Ib, and III can prevent of invasive disease caused by GBS in the study area. Neonatal GBS disease can be classified as early-onset disease (EOD), which occurs in less than 7 days after birth and late onset-disease (LOD) which occurs in between 7 and 90 days after birth3.In 1970 GBS emerged as a the main cause of neonatal morbidity and mortality in the United States of America (USA) and other industrialized countries4. The maternal GBS colonization rate varies in different settings. The lowest colonization rate was reported from India, 7.6%5 and the highest was reported from Norway, 34.8%6. Factors such as prolonged rupture of membrane, prematurity, chorioamnionitis, low level of anti-GBS capsular antibody and previous newborn with EOD can increase the risk of disease among newborns8. Newborns can acquire the disease due to vertical transmission of GBS from the colonized mother to their newborns in utero or during passage through birth canal. The transmission mechanism for LOD is not well known8.The primary risk factor for EOD is rectovaginal colonization of pregnant women with GBS during delivery1.Administration of Intrapartum Antibiotic Prophylaxis (IAP) for GBS colonized pregnant women before delivery or for pregnant women with risk factors can reduce EOD due to GBS. The prevention strategy, IAP, was issued in 1996 by a different organization and professional association in the USA. The strategy when first released, it reduced a significant amount of EOD caused by GBS. The strategy was updated in 2002 and 2010 to further reduce neonatal disease caused by GBS3. Use of IAP has reduced about 80% burden of EOD due to GBS, out of 1.8 newborns per 1000 live births in the 1990s to 0.23 newborns per 1000 live births in 20159.Even though IAP has substantially reduced EOD caused by GBS, it has several limitations. The strategy does not eliminate all cases of EOD; it does not affect LOD caused by GBS and there is a concern of the selection of antimicrobial resistance bacteria10. However as GBS serotypes vary from place to place and from time to time the current vaccine formulation may not work equally for all countries8. As a result data on epidemiology of GBS serotype is required from every country. In Ethiopia, there is scarce data on maternal GBS colonization and GBS serotype distribution. Therefore, this study was sought to provide valuable data on maternal and newborns GBS colonization rate, associated risk factors and serotypes distribution.Above all, screening based IAP is not feasible for developing countries where resource is limited for laboratory diagnosis. As an alternative, the capsular polysaccharide based vaccine is being developed; currently, vaccine formulation which contains GBS serotype such as Ia, Ib, and III has completed phase II clinical trial and it was reported to be cost-effectiveAdama Hospital Medical College (AHMC) is located at Adama City, Oromiya regional state; it is located 100 km due east of Addis Ababa. The City has a total population of 220,212. It is located at 8°33′N39°16′E/8.55°N39.27°E at an elevation of 1712 meters.A Hospital-based cross-sectional study was conducted from June 2014-October 2014 at Adama Hospital Medical College, Adama, Ethiopia.11.Out of pregnant women who were admitted at Adama Hospital Medical College for delivery during the study period, 280 along with their newborns were consented and screened for GBS colonization. Two hundred eighty pregnant women who fulfilled the inclusion criteria were recruited based on a convenience sampling technique. Neonates born from GBS colonized mother were followed through telephone for 7 days. The sample size was calculated by using a single proportion formula, margin of error = 0.05, Confidence Interval = 95%, and prevalence from previous study conducted in Ethiopia, 20.86%Pregnant women with normal delivery were included. Pregnant women who were on antibiotic for the last three weeks and cesarean-section delivery were excluded.Maternal and newborn GBS colonization rate, Serotype distributionAssociated factors12.Rectovaginal specimens were collected from pregnant women and the specimen was collected from nasal area, external ear, umbilical cord and throat of the newborns by the trained midwifery from informed and consented pregnant women before delivery and was placed in labeled Stuart’s transport media . The specimens were transported to the Microbiology Laboratory within 4 hours after collection. Socio-demographic and clinical data were collected by using a structured questionnaire2 atmosphere. On the next day, it was sub-cultured onto sheep blood agar plate  and incubated in the CO2 enriched atmosphere for 18 − 24 hours. If GBS was not detected, the blood agar plate was re-incubated and examined after 48 hours to detect GBS. All colonies which were beta-hemolytic, or non-hemolytic, Gram positive cocci, catalase-negative was sub-cultured and isolated for confirmatory testing. A bacteria which was CAMP test positive was considered as GBS. CAMP test culture results were re-tested using a Strp B Grouping Latex .All specimens collected from pregnant women and newborns were placed in selective media, Lim broth . After inoculation, the media was incubated for 18–24 hours, at 37 °C in COet al.13. GBS strain for serotyping was prepared first by growing on blood agar plates and then a heavy suspension of the test organism was prepared by using phosphate-buffered saline (PBS). A 20 µl aliquot of the bacterial suspension was placed on a disposable reaction card and mixed with 1 µl of latex suspension . The card was rotated and observed for agglutination. A positive reaction was confirmed whenever agglutination appeared within the 30 s. All methods were performed in accordance with the relevant guidelines and regulations12GBS isolates were serotyped by using type-specific 10 antisera for serotypes Ia, Ib, II, III, IV, V, VI, VII, VIII, and IX  as described by Slotved Streptococcus pyogenes (ATCC 19615), Streptococcus agalactiae (ATCC12403), and Staphylococcus aureus (ATCC 24923), during the study. The manufacture’s instruction was followed and negative and positive controls were during serotyping. To maintain the consistency, 5% of structured questionnaire were pretested at different hospital. To ensure the viability of GBS, all samples were placed in transport media immediately after collection and processed within four hours of collection.As part of quality in the study, we have included control strains such as Data entry and analysis were done using computer with SPSS version 20 software. Prevalence figures were calculated for the total study population and separately by age group and risk factors. Logistic regression was used to a compare the results obtained from pregnant women and their newborns with different age groups, risk factors. A P-value less than 0.05 was considered significant.The study was approved by the Institutional Review Board of College of Health Science, Addis Ababa University (Ref No: 069/13/DMIP) and the National Ethics and Research Committee (Ref No: 3.10/795/06). Written informed consent was obtained from all study participants. Written informed consent was also obtained from mothers to collect samples from their newborns. A guideline was followed as per the declaration of Helsinki for involving human participants in the study.A total of 280 pregnant women along with their 282 newborns participated in this study. Majority of the participants were from Adama city 193(68.9%) followed by Lume 17(6.9%) and Fentale 11(3.9%). Most of the study participants were housewives 264(94.3%), followed by Nurses and Merchant. Two hundred one (71.8%) of the study participants were within the age range of 15–27 years. One hundred thirty seven (48.6%) newborns were males, and 145(51.4%) were females.Among 280 pregnant women participated in the present study, 241(86.1%) delivered at gestational age of 37–42 ; 150(53.6%) were primigravida; 1(0.4%) had a history of newborns who developed EOD; 120(42.8%) had a previous history of vaginal delivery; 206(73.6%) had duration of rupture of membrane of 0–5 hours; 25 (9.3%) had premature rupture of membrane (PROM)  were alive during birth; 246 (87.2%) were in weight range of 2500–4000 g; 179 (63.5%) had Appearance, Pulse, Grimace, Activity, Respiration (APGAR) score at 5 minutes >7; 247 (87.6%) had APGAR score at 10 minutes >7; 18 (6.4%) were newborns with other abnormalities , 8(21.6%), 10(27%), 3(8.1%), 8, 1(2.7%), and 1(2.7%) respectively. Out of 21 GBS strained recovered from newborns the distribution of serotypes of Ia, Ib, II, III, V, VII were 3(14.3%), 6(28.6%), 6(28.6%), 4(19%), 1(4.8%), and 1(4.8%) respectively. All positive children have the same serotypes as their respective mothers 15, Eastern Ethiopia (13.68%)16, Namibia (13.6%)17, Kenya (12%)18, Western Cape, South Africa (16.6%)19. Previous study conducted in Hawassa showed higher maternal GBS colonization rate than this study20. Our finding is low compared to GBS colonization rate reported from Congo (20%)21, Malawi (21.7%)22, Greter Acra (26.8)23, Uganda (28.8%)24, South Africa (28.4%)25, Zimbabwe (31.6%)26, South Africa (37%)17, Egypt (26.25%)27, Tanzania (23%)28, Jordan (19.5%)29, and Gabon (19%)30. However, it was high compared to Nigeria (8.3%)31 and Sudan (0.5%)32. Maternal GBS colonization rate found in the present study was comparable to maternal GBS colonization rate reported from Brazil (14.6%)33 Thai-Myanmar (12%)34, however, it is low compared to Germany (16%)35, USA (21%)36, Sweden (25.4%)37, The Netherlands (21%)38, and New Zealand 20%39.Maternal GBS colonization rate found in this study (13.2%) was comparable with maternal GBS colonization rate reported from Nekemte, Ethiopia (12.2%)25. Use of selective media, such as limborth instead of direct plating on blood agar increase the positivity rate. Taking sample both from vagina and rectal area increase the positivity rate as compared to swabbing only from the vagina1.There are several reasons for the variation of maternal GBS colonization rates in different countries and within the countries. The variation can be a true difference or it can be due to laboratory methods used, time and site of sample collection3. In the present study, 7.4% of newborns were colonized with GBS, which is in line with earlier studies conducted in industrialized countries41. Out of 21 GBS colonized newborns in the present study one of them developed signs and symptoms of EOD as followed by telephone interviews. In this study, out of 13 newborns who were not alive during birth one of them was colonized with GBS. Since other studies are also linking stillbirth with GBS, this area needs further investigation4.About 50% of newborns from GBS colonized mothers are GBS positive during birth. Most newborns who acquire GBS during passage through the birth canal remain healthy. About 1–3% of them may develop invasive disease7. In this study no significant association between GBS colonization rate and the measured risk factors were found (P > 0.05).Group B streptococcus colonization rate varies according to region, ethnicity, socioeconomic status, maternal age, gestational age less than 37, and prolonged rupture of the membrane42. GBS serotype distribution varies geographically and over time43. In European countries, The United States and in South America serotypes Ia, Ib, III or V are the most frequently reported GBS serotypes. From Japan serotype VI and VII are frequently reported43. The invasiveness of GBS also varies according to GBS serotypes; serotype III is believed to be the most virulent GBS serotypes43.Capsular polysaccharide-based serotyping has been applied for epidemiological studies of GBS and it is important in the development of multivalent vaccines containing several serotypes45. The prevalence of serotype III in our study is low compared to the report from many other countries43. A study from S. Africa reported high serotype Ia (39.2%), III (32.8%) compared to our study25, however, they have reported comparable prevalence of serotype V (12.4%)25. The prevalence of serotype Ia in this study was comparable to a study conducted in Zimbabwe (17%)26, but they have reported a high prevalence of serotype III (47.7%) and V (23.2%) than our finding26. Compared to our study, a low prevalence of serotype II (6.4%) and high prevalence of serotype V (30.3%), III (27.5%) was reported from Gabon. The prevalence of serotype Ia (12.8%), Ib (22.9%) is comparable with our study26.In the present study, the prevalent serotype was serotype II (27.6%) followed by serotype Ib (24.1%), Ia (15.5%), and V (15.5%). The finding of this study was in partial agreement with GBS serotypes reported from other countrieset al. (2012) in their review, reported that serotype III to be the most common (48.9%) among different geographic areas including in Africa, followed by serotypes Ia, Ib, II, and V. A trivalent  the conjugate vaccine developed by Novartis was shown to be effective. However, the distribution of serotype is not uniform in different countries and it will change over time. To solve this problem, Pfizer, in 2017, started to evaluate a Pentavalent GBS polysaccharide capsular vaccine containing GBS serotype Ia, Ib, II, III, and V48. Both trivalent and Pentavalent vaccine does not contain all GBS serotypes: IV, VI, VII, VIII, and IX are missed from the formulation. This indicates data on GBS serotype distribution from each country is highly required for appropriate vaccine formulation.Edmonds As we have used convenience sampling technique the finding of this study may not represent all pregnant mothers in the study area. In this study we did not used all known serotypes of GBS for quality control as they are not available locally.Group B streptococci have been recognized as the leading cause of infectious meningitis in infants in high-income countries but its importance in developing countries is not clear. The primary risk factor for EOD due to the GBS is GBS colonization of pregnant women before delivery. Maternal and newborns GBS colonization rate and GBS serotype distribution in this study is similar to other countries. The most prevalent GBS serotypes detected in our study include; serotype II, Ib, Ia, V, and III. Vaccine covering these five serotypes may prevent most of EOD due to GBS in our study area if the disease-causing GBS serotypes is similar to colonizing GBS serotypes. Based on this study we recommend large scale surveillance of neonatal disease due to GBS, circulating serotypes and adoption of prevention strategy.