Indian Academy of Pediatrics Consensus Statement on Diagnosis and Management of Bone and Joint Infections in Children.

JUSTIFICATION: Osteoarticular infections are fairly common in children but often these are associated with underdiagnosis, delayed diagnosis and improper management. This leads to an increased incidence of complications and poor outcomes. Given the paucity of standard protocols for the management of these children in the Indian context, Indian Academy of Pediatrics (IAP) has taken the initiative to formulate guidelines for the early diagnosis and rational management of bone and joint infections (BJIs). OBJECTIVES: To critically evaluate the current evidence and formulate consensus guidelines for the diagnosis and management of BJIs in children. PROCESS: A committee comprising of eminent national faculty from different parts of the country who are experts in the field of Pediatric Infectious Diseases, Pediatric Orthopedics and Musculoskeletal Radiology was constituted and duly approved by the IAP. On Jan 16, 2021, a virtual meeting was held and a detailed discussions were carried out regarding the need to formulate these guidelines. Subsequently, the expert group defined the key questions in the first stage followed by collection and review of scientific evidences including available national and international recommendations or guidelines. This was followed by detailed deliberation among group members and presentation of their recommendations. The same were finalized in an online meeting on Aug 01, 2021, and a consensus statement was developed and adopted by the group. STATEMENT: BJIs are medical emergencies that need early diagnosis and appropriate therapy to prevent long term sequelae like limb deformities. Bacterial infections like Staphylococcus aureus is the most common etiological agent. Nonspecific and subtle clinical manifestations make the diagnosis of pediatric BJIs more challenging. Diagnosis of BJIs is primarily clinical, supplemented by laboratory and radiological investigations. The choice of antibiotic(s), mode of administration and duration of therapy requires individualization depending upon the severity of infection, causative organism, regional sensitivity patterns, time elapsed between onset of symptoms and the child's presentation, age, risk factors and the clinical and laboratory response to treatment. There is paucity of appropriate guidelines regarding the diagnosis and management of BJIs in children in Indian context. Hence, the need for this expert consensus guidelines in Indian settings.

A Real-World Perspective of Co-amoxiclav Prescription Pattern With Probiotics for Pediatric Patients With Respiratory Tract Infections: Results of Quantitative and Qualitative Approach in Indian Outpatient Settings.

BACKGROUND: Probiotics are co-prescribed with co-amoxiclav to prevent antibiotic-associated diarrhea (AAD). The study assesses the co-prescription pattern of probiotics with co-amoxiclav in pediatric patients with respiratory tract infections (RTIs). METHODS: This was a mixed methods research study with a retrospective study and a prospective survey. The retrospective part included a multicenter, observational, real-world study utilizing patients' electronic medical records for three years (2018-2020) from seven outpatient pediatric clinics and hospitals. The qualitative evaluation was performed with a predefined questionnaire. RESULTS: The patients having RTIs (N=984) were prescribed Clamp® (46.7%), CAA (23.8%), and CAM (29.5%). The mean age of the patients was 4.05 years, with 59.25% males and most patients having upper RTIs. Co-amoxiclav was prescribed twice daily for one to 15 days. A significantly lesser number of probiotic co-prescriptions were observed with Clamp® (19.57%) than with CAA (38.46%) and CAM (29.31%) at baseline (p<0.001). Similar findings were observed for follow-up visits one and two. Saccharomyces boulardii, Bacillus clausii,and lactic acid bacillus were the most commonly co-prescribed probiotics. The qualitative evaluation indicated that most clinicians were aware of the co-amoxiclav-related gastrointestinal side effects and the benefits of probiotics in preventing them. CONCLUSION: The frequency of co-prescriptions of probiotics with Clamp® among pediatric patients with RTIs was significantly less, potentially indicating better gastrointestinal tolerability.

Pertussis in India: Past, Present, and Future.

While vaccines have markedly reduced the incidence of pertussis, a resurgence has occurred in many countries. Until recently, pertussis has not been recognized as an important public health challenge in India due to its successful infant immunization program. However, India still accounts for a large proportion of the world's cases, and increasing reports of pertussis in other countries and in neonates have regenerated interest in pertussis among Indian authorities. The Global Pertussis Initiative (GPI) Annual Meeting was held virtually in October 2020, in part, to gain a better understanding of the epidemiology and disease burden of pertussis and to explore opportunities to improve its prevention in India. There was a consensus that pertussis cases are being underestimated in India due to multiple factors, such as a reliance on passive surveillance and diagnostic challenges. India offers both whole-cell pertussis and acellular pertussis vaccines, but vaccine coverage is inconsistent across regions due to differences in vaccine availability, access to health care, and regional administrative challenges. This report summarizes the outcomes and considers the key clinical implications of this meeting. The GPI agreed that active surveillance of pertussis in India would be optimal and recommended several studies, including serosurveillance among women of reproductive age to assess the prevalence of recent pertussis infection and to enable policy changes that will enhance the rational use of acellular and whole-cell vaccines. It also recommended engagement with nongovernmental organizations in order to encourage pregnancy immunization in the public sector. To achieve effective control of pertussis in the future, the GPI recognizes there are opportunities to characterize the burden of pertussis in India appropriately and increase vaccination coverage in multiple age groups.

Burden of varicella in the Asia-Pacific region: a systematic literature review.

INTRODUCTION: Varicella is a highly contagious infection that can lead to serious complications, particularly in high-risk groups; however, it is vaccine preventable. Disease awareness and understanding of the disease burden can strongly influence vaccine coverage. This review provides insight into the current epidemiology and the importance of varicella from both public health and economic perspectives across the Asia-Pacific (APAC) region. Areas covered: A systematic literature review was conducted to identify studies on the incidence, seroprevalence, fatality rate and complication rate of varicella. Economic burden studies were also captured. Altogether, 125 studies were identified across the region; these were supplemented by government reports (gray data). Reported vaccine coverage varied from 2.8% to 97%; a key influencing factor was inclusion of the varicella vaccine in national immunization programs. In general, varicella incidence in the unvaccinated population was highest in children ≤5 years old and seroprevalence increased with age. Economic analyses highlighted the cost-saving potential of vaccination programs, especially from a societal perspective. Expert opinion: Varicella-related data varied greatly across the APAC region, highlighting the need to better understand the burden of varicella in this area, and particularly identified the need for better surveillance and reporting.

Safety and immunogenicity of Bio Pox™, a live varicella vaccine (Oka strain) in Indian children: A comparative multicentric, randomized phase II/III clinical trial.

Varicella or chickenpox is a highly contagious disease with a high secondary attack rate. Almost 30% of Indian adolescents lack protective antibodies against varicella, emphasizing the need of routine varicella immunization. The Oka VZV is a well-established, safe and efficacious vaccine strain that is highly immunogenic and produces lifelong protective immunity. The present multicentric, open label, randomized, controlled Phase II/III study, compared the Bio Pox™ (indigenous investigational vaccine) with a licensed vaccine, Varivax™ [a][a] Please note that this article refers to the product named VARIVAX as manufactured by Changchun Keygen Biological Products Ltd., China and marketed in India by VHB Life Sciences Limited, Mumbai, and not the product VARIVAX® owned by Merck Sharp & Dohme Corp., Rahway, New Jersey, USA. Merck Sharp & Dohme Corp. have asked us to make clear that the product manufactured by Changchun Keygen Biological Products Ltd. is unrelated to and is not sponsored, endorsed or otherwise authorised by Merck Sharp & Dohme Corp. , for its safety and immunogenicity profile in 252 healthy subjects in the age group of 1-12 y (cohort I: 6-12 years, II:1-6 years) in 3 tertiary medical institutions. Antibodies were measured by VZV Glycoprotein Enzyme Linked Immunoassay (IgG ELISA) kit. Seroconversion percentage in children having pre-vaccination anti VZV IgG titer <10 mIU/mL (< 5 gp ELISA units/mL) were 80% for Bio Pox™ and 77% for Varivax™ (p = 0.692). The seroconversion rate in the group receiving Bio Pox™ was non-inferior to the group that received Varivax™. There were mild local reactions for both the vaccines; none of the patient had fever or required hospitalization or medication. The Bio Pox™ was found to be safe and immunogenic in children against VZV infection.

Reactogenicity and safety of the human rotavirus vaccine, Rotarix™ in The Philippines, Sri Lanka, and India: a post-marketing surveillance study.

Regulatory bodies in The Philippines, Sri Lanka, and India require post-marketing surveillance to provide additional safety data on Rotarix™ in real-life settings. In such studies conducted in The Philippines (November 2006 to July 2012; NCT00353366), Sri Lanka (November 2008 to August 2009; NCT00779779), and India (August 2009 to April 2010; NCT00938327), 2 doses of Rotarix™ were administered according to the local prescribing information (PI). The occurrence of at least Grade "2"/"3" solicited adverse event (AE) (fever, vomiting, or diarrhea), within 15 days in The Philippines or 8 days in Sri Lanka and India; unsolicited AEs within 31 days and serious adverse events (SAEs) throughout the study were recorded. Of the 1494, 522, and 332 infants enrolled in The Philippines, Sri Lanka, and India, 14.7% 14.9% and 12.7% infants, respectively recorded at least Grade "2"/"3" solicited AEs. The most commonly reported solicited AEs were irritability in The Philippines (32.2% post-Dose-1; 23.5% post-Dose-2) and India (23.0% post-Dose-1; 13.2% post-Dose-2), and fever (18.0% post-Dose-1; 20.2% post-Dose-2) in Sri Lanka. Unsolicited AEs were recorded in 24.5% (The Philippines), 4.8% (Sri Lanka), and 6.9% (India) of infants. Forty-one SAEs were recorded in the Philippines of which 6 (decreased oral intake with increased sleeping time and constipation; pneumonia, urinary tract infection, and intussusception) were considered by the investigators as causally related to vaccination. One vaccine-unrelated SAE occurred in a Sri Lankan infant. All SAEs resolved and the infants recovered. Two doses of Rotarix™, administered to healthy infants according to local PI, were well tolerated in The Philippines, Sri Lanka, and India.

Immunogenicity and safety of live attenuated hepatitis A vaccine: a multicentric study.

OBJECTIVE: To evaluate immunogenicity and tolerability of single dose live attenuated injectable hepatitis A vaccine in four metropolitan cities of India. METHODS: Live attenuated hepatitis A vaccine was administered to 505 children aged 18 to 60 months in four centers across India. Immunogenicity of the vaccine was assessed by estimation of anti-HAV antibody titer at 6 weeks and 6 months following administration of the vaccine. Safety evaluation of the vaccine was also done during the visits. RESULTS: At 6 weeks, 480 subjects (95%) came for the follow-up and 411 (81.4%) subjects reported at the end of 6 months. The geometric mean titer (GMT) of anti-HAV antibody of the subjects who did not have the seroprotective titer at the baseline were assessed at 6 weeks and 6 months which was 81.04 mIU/ml and 150.66 mIU/ml respectively. At 6 weeks, 95.1 % seroconverted and at the end of 6 months, 97.9 % had seroconverted. Both solicited and unsolicited vaccine-induced local and systemic adverse events were insignificant at all the centers, except swelling and induration in a few. CONCLUSION: Live attenuated injectable hepatitis A vaccine was immunogenic and tolerable with minimal reactogenecity, in this study of single dose schedule. Safety profile was also satisfactory in the study population.

Spontaneous rupture of malarial spleen.

Spontaneous rupture of malarial spleen is uncommon even in highly endemic areas of malaria. We report an eight year old girl who presented with spontaneous splenic rupture following malaria. She recovered with conservative management.