Estimated public health impact of human rotavirus vaccine (HRV) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV) on child morbidity and mortality in Gavi-supported countries.

Vaccine impact models against rotavirus disease (RD) and pneumococcal disease (PD) in low- and middle-income countries assume vaccine coverage based on other vaccines. We propose to assess the impact on severe disease cases and deaths avoided based on vaccine doses delivered by one manufacturer to Gavi-supported countries. From the number of human rotavirus vaccine (HRV) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV) doses delivered, we estimated the averted burden of disease 1) in a specific year and 2) for all children vaccinated during the study period followed-up until 5 years (y) of age. Uncertainty of the estimated impact was assessed in a probabilistic sensitivity analysis using Monte-Carlo simulations to provide 95% confidence intervals. From 2009 to 2019, approximately 143 million children received HRV in 57 Gavi-supported countries, avoiding an estimated 18.7 million severe RD cases and 153,000, deaths. From 2011 to 2019, approximately 146 million children received PHiD-CV in 36 countries, avoiding an estimated 5.0 million severe PD cases and 587,000 deaths. The number of severe cases and deaths averted for all children vaccinated during the study period until 5 years of age were about 23.2 million and 190,000, respectively, for HRV, and 6.6 million and 749,000, respectively, for PHiD-CV. Models based on doses delivered help to assess the impact of vaccination, plan vaccination programs and understand public health benefits. In 2019, HRV and PHiD-CV doses delivered over a 5-y period may have, on average, averted nine severe disease cases every minute and one child death every 4 min.

What is the context?The WHO added the pneumococcal conjugate vaccine and the rotavirus vaccine in the recommended vaccination schedule of all countries in 2007 and 2009, respectively.Previous studies estimated the public health benefit of these vaccines by approximating the number of children who received them.What is new?We used an alternative approach to estimate the benefit based on actual number of doses of the vaccines, human rotavirus vaccine (HRV; Rotarix) and pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV; Synflorix) delivered to each country considered.The study analyzed data from children under 5 years of age in 60 Gavi-supported countries by identifying the number of vaccine doses delivered, estimating the number of children fully covered, applying the country-specific disease epidemiology, estimating the number of severe disease cases and deaths avoided.From 2009 to 2019, approximately 143 million children were vaccinated with HRV avoiding an estimated 18.7 million severe rotavirus disease cases and 153,000 deaths.From 2011 to 2019, about 146 million children were vaccinated with pneumococcal vaccine avoiding an estimated 5.0 million severe pneumococcal disease cases and 587,000 deaths.What is the impact? The benefit of HRV and PHiD-CV in Gavi-supported countries is often estimated based on assumptions of vaccine coverage rates.A modeling approach based on doses delivered by the vaccine manufacturer can provide an additional view on the potential vaccine benefits and improve planning, contribution, and sustainability of the immunization programs at a country level.In 2019, HRV and PHiD-CV together averted nine cases of severe disease each minute and one child death every 4 minutes.

The Burden of Acute Febrile Illness Attributable to Dengue Virus Infection in Sri Lanka: A Single-Center 2-Year Prospective Cohort Study (2016-2019).

We performed a 2-year prospective cohort study to determine the incidence of dengue in Angoda, Colombo district, Sri Lanka (NCT02570152). The primary objective was to determine the incidence of acute febrile illness (AFI) because of laboratory confirmed dengue (LCD). Secondary objectives were to determine AFI incidence because of non-LCD, describe AFI symptoms, and estimate AFI incidence because of LCD by dengue virus (DENV)-type and age group. Participants from households with at least one minor and one adult (≤50 years) were enrolled and followed with scheduled weekly visits and, in case of AFI, unscheduled visits. Blood was collected for DENV detection at AFI visits, and symptoms recorded during the 7-day period following AFI onset. A total of 2,004 participants were enrolled (971 children, and 1,033 adults). A total of 55 LCD episodes were detected (overall incidence of 14.2 per 1,000 person-years). Incidence was the highest among children < 5 years (21.3 per 1,000 person-years) and 5-11 years (22.7 per 1,000 person-years), compared with adults ≥ 18 years (9.2 per 1,000 person-years). LCD was mostly (83.6%) caused by DENV-2 (n = 46), followed by DENV-1 (n = 6) and DENV-3 (n = 3). Common symptoms of LCD were headache, fatigue, myalgia, loss of appetite, and arthralgia. Incidence of AFI because of non-LCD was 47.3 per 1,000 person-years. In conclusion, this study reports the LCD incidence for a DENV-2 dominated epidemic that is comparable to the incidence of suspected dengue reported passively for 2017, one of the worst outbreaks in recent history.

Immunogenicity and safety of 3-dose primary vaccination with combined DTPa-HBV-IPV/Hib in Indian infants.

Multivalent combination vaccines have reduced the number of injections and therefore improved vaccine acceptance, timeliness of administration and global coverage. The hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenzae type b (DTPa-HBV-IPV/Hib; Infanrix hexa™) vaccine, administered according to various schedules, is widely used for the primary vaccination of infants worldwide. In the current publication, we are presenting the immunogenicity and safety of 3 doses of DTPa-HBV-IPV/Hib vaccine when administered to Indian infants. 224 healthy infants (mean age 6.8 weeks) were vaccinated at 6-10-14 weeks (W) of age (n = 112) or 2-4-6 months (M) of age (n = 112). One month after the third vaccine dose, the seroprotection/seropositivity status against diphtheria, pertussis, tetanus, polio, hepatitis B and Hib antigens ranged from 98.6% to 100% in both groups. The vaccine response rate to the pertussis antigens ranged from 97% to 100%. Pain (6-10-14W group: 25.2%; 2-4-6M group: 13.4%) and fever (15.3% and; 15.2%, respectively) were the most frequently reported solicited local and general symptoms. Unsolicited adverse events were reported for 35.7% (6-10-14W group) and 22.3% (2-4-6M group) of subjects. No vaccine related serious adverse events were reported. In conclusion, the hexavalent DTPa-HBV-IPV/Hib vaccine was immunogenic and well tolerated, irrespective of the dosing schedule.

Bioaccumulation of heavy metals by freshwater algal species of Bhavnagar, Gujarat, India.

The present study investigated copper, cadmium, lead and zinc accumulation in algal species Oedogonium, Cladophora, Oscillatoria and Spirogyra from freshwater habitats of Bhavnagar, India. Eight different locations were periodically sampled during August 2009 to March 2011. The general trend of heavy metal concentrations in all the algal species in present study (except at few stations), were found to be in the following order: Zn > Cu > Pb > Cd. Highest accumulation of Cu was recorded in Oedogonium, while Cladophora showed highest accumulation of Pb signifying a good bioaccumulator. Oscillatoria and Oedogonium were highest Zn accumulating algae which showed significant difference between the means at P < 0.05. ANOVA was performed for comparing significance mean between the groups and within the group for heavy metals in water. The concentration of heavy metals in water was in the following order: Zn > Cu > Pb > Cd. The present study showed that Oedogonium, Cladophora, Oscillatoria and Spirogyra were excellent bioaccumulator and could be utilized as biomonitoring agents in water bodies receiving waste contaminated by metals.

Immunogenicity and safety of early vaccination with two doses of a combined measles-mumps-rubella-varicella vaccine in healthy Indian children from 9†months of age: a phase III, randomised, non-inferiority trial.

OBJECTIVE: This study (NCT00969436) compared the immunogenicity and safety of measles-mumps-rubella (MMR) followed by MMR+varicella (V) vaccines to (1) 2 doses of combined MMRV and (2) MMR followed by MMRV, in Indian children. DESIGN: Phase III, open, randomised, non-inferiority study. SETTING: 6 tertiary care hospitals located in India. PARTICIPANTS: Healthy participants aged 9-10 months not previously vaccinated against/exposed to measles, mumps, rubella and varicella or without a history of these diseases. INTERVENTIONS: Participants were randomised (2:2:1) to receive 2 doses of either MMRV (MMRV/MMRV group) or MMR followed by MMRV (MMR/MMRV group) or MMR followed by MMR+V (MMR/MMR+V, control group) at 9 and 15 months of age. Antibody titres against measles, mumps and rubella were measured using ELISA and against varicella using an immunofluorescence assay. MAIN OUTCOME MEASURES: To demonstrate non-inferiority of the 2 vaccination regimens versus the control in terms of seroconversion rates, defined as a group difference with a lower bound of the 95% CI >-10% for each antigen, 43 days postdose 2. Parents/guardians recorded solicited local and general symptoms for a 4-day and 43-day period after each vaccine dose, respectively. RESULTS: Seroconversion rates postdose 1 ranged from 87.5% to 93.2% for measles, 83.3% to 86.1% for mumps and 98.7% to 100% for rubella across the 3 vaccine groups. The seroconversion rates postdose 2 were 100% for measles, mumps and rubella and at least 95.8% for varicella across the 3 vaccine groups. Non-inferiority of MMRV/MMRV and MMR/MMRV to MMR/MMR+V was achieved for all antigens, 43 days postdose 2. The 3 vaccination regimens were generally well tolerated in terms of solicited local and general symptoms. CONCLUSIONS: The immune responses elicited by the MMRV/MMRV and MMR/MMRV vaccination regimens were non-inferior to those elicited by the MMR/MMR+V regimen for all antigens. The 3 vaccination schedules also exhibited an acceptable safety profile in Indian children. TRIAL REGISTRATION NUMBER: NCT00969436.

Hepatotropic viruses as etiological agents of acute liver failure and related-outcomes among children in India: a retrospective hospital-based study.

BACKGROUND: Acute liver failure (ALF) is marked by a sudden loss of hepatic function and is associated with a high mortality rate in children. The etiology of ALF is shown to vary geographically. This study assessed the frequency of hepatotropic viruses as etiological agents of ALF in Indian children. METHODS: This retrospective study enrolled children aged 0-18 years with confirmed ALF admitted to Christian Medical College, Vellore and King Edward Memorial Hospital and Research Center, Pune between January 2003 and December 2005. The frequency of hepatotropic viruses as etiological agents in children with ALF aged ≤18 years was calculated with 95% confidence interval (CI). Descriptive analyses of demographic characteristics, clinical signs and symptoms of ALF, choice of treatment and outcomes were performed. RESULTS: Of 76 children enrolled, 54 were included in the per-protocol analyses. Mean age of children with ALF was 5.43 years (standard deviation = 3.62); 51.9% (28/54) were female. The percentage of children positive for anti-hepatitis A virus (HAV) IgM and hepatitis B surface antigen was 65.9% (27/41; 95% CI 49.4-79.9) and 15.9% (7/44; 95% CI 6.6-30.1), respectively. The final cause of ALF was HAV (36.3%) followed by hepatitis B virus (HBV; 8.8%). Before and during admission, encephalopathy was observed in 77.8% (42/54) and 63.0% (34/54) of children, respectively. A high number of children (46/54; 85.2%) required intensive care and ALF was fatal in 24.1% (13/54). The proportion of deaths due to HAV and HBV was 18.5% (5/27) and 57.1% (4/7), respectively. CONCLUSIONS: HAV and HBV were the most common etiological agents of ALF in Indian children. Primary prevention by vaccination against HAV and HBV in young children may be useful in the prevention of ALF due to viral hepatitis in India.

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.

Randomized, open-label study of the impact of age on booster responses to the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in children in India.

In this phase III, open-label, multicenter, and descriptive study in India, children primed with 3 doses (at ages 6, 10, and 14 weeks) of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were randomized (1:1) to receive a booster dose at 9 to 12 (early booster) or 15 to 18 months old (late booster) in order to evaluate impact of age at booster. We also evaluated a 2-dose catch-up vaccination plus an experimental booster dose in unprimed children age 12 to 18 months. The early booster, late booster, and catch-up vaccinations were administered to 74, 95, and 87 children, respectively; 66, 71, and 81 children, respectively, were included in the immunogenicity according-to-protocol cohort. One month postbooster, for each PHiD-CV serotype, ≥95.2% (early booster) and ≥93.8% (late booster) of the children had antibody concentrations of ≥0.2 µg/ml; ≥96.7% and ≥93.0%, respectively, had opsonophagocytic activity (OPA) titers of ≥8. The postbooster antibody geometric mean concentrations (GMCs) were in similar ranges for early and late boosters; the OPA titers appeared to be lower for most PHiD-CV serotypes (except 6B and 19F) after the early booster. After dose 2 and postbooster, for each PHiD-CV serotype, ≥88.6% and ≥96.3%, respectively, of the catch-up immunogenicity according-to-protocol cohort had antibody concentrations of ≥0.2 µg/ml; ≥71.4% and ≥90.6%, respectively, had OPA titers of ≥8. At least 1 serious adverse event was reported by 2 children in the early booster (skin infection and gastroenteritis) and 1 child in the catch-up group (febrile convulsion and urinary tract infection); all were resolved, and none were considered by the investigators to be vaccine related. PHiD-CV induced robust immune responses regardless of age at booster. Booster vaccination following 2 catch-up doses induced robust immune responses indicative of effective priming and immunological memory. (These studies have been registered at www.clinicaltrials.gov under registration no. NCT01030822 and NCT00814710; a protocol summary is available at www.gsk-clinicalstudyregister.com [study ID 112909]).

Human papillomavirus prevalence and type-distribution in women with cervical lesions: a cross-sectional study in Sri Lanka.

BACKGROUND: Cervical cancer ranks second among all cancers reported in Sri Lankan women. This study assessed the prevalence and type-distribution of human papillomavirus (HPV) among Sri Lankan women with invasive cervical cancer (ICC) and pre-cancerous lesions. METHODS: 114 women aged 21 years and above, hospitalized in the National Cancer Institute, Sri Lanka with a diagnosis of ICC or cervical intraepithelial neoplasia (CIN) 2/3 were prospectively enrolled between October 2009 and September 2010 (110430/NCT01221987). The cervical biopsy or excision specimens collected during routine clinical procedures were subjected to histopathological review. DNA was extracted from samples with a confirmed histological diagnosis and was amplified using polymerase chain reaction and HPV DNA was detected using Enzyme Immuno Assay. HPV positive samples were typed using reverse hybridization Line Probe Assay. RESULTS: Of the cervical samples collected, 93.0% (106/114) had a histologically confirmed diagnosis of either ICC (98/106) or CIN 2/3 (8/106). Among all ICC cases, squamous cell carcinoma was diagnosed in the majority of women (81.6% [80/98]). HPV prevalence among ICC cases was 84.7% (83/98). The HPV types most commonly detected in ICC cases with single HPV infection (98.8% [82/83]) were HPV-16 (67.3%) and HPV-18 (9.2%). Infection with multiple HPV types was recorded in a single case (co-infection of HPV-16 and HPV-59). CONCLUSIONS: HPV was prevalent in most women with ICC in Sri Lanka; HPV-16 and HPV-18 were the predominantly detected HPV types. An effective prophylactic vaccine against the most prevalent HPV types may help to reduce the burden of ICC disease.

Immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal non-typeable Hemophilus influenzae protein D conjugate vaccine (PHiD-CV) when co-administered with the DTPw-HBV/Hib vaccine in Indian infants: a single-blind, randomized, controlled study.

In India, pneumococcal diseases are major causes of child mortality, and effective vaccines against Streptococcus pneumoniae are needed. This single-blind, randomized study assessed the immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Hemophilus influenzae (NTHi) protein D conjugate vaccine (PHiD-CV) co-administered with DTPw-HBV/Hib in Indian infants as 3-dose primary vaccination course. A total of 360 infants were randomized (2:1) to receive either PHiD-CV co-administered with DTPw-HBV/Hib (PHiD-CV group) or a Hib vaccine co-administered with DTPw-HBV (control group) at 6, 10, and 14 weeks of age. For each vaccine pneumococcal serotype, the percentage of infants in the PHiD-CV group with antibody concentrations ≥ 0.2 µg/mL one month after the third vaccine dose was at least 98.3%, except for serotypes 6B (77.7%) and 23F (89.5%), and opsonophagocytic activity titers ≥ 8 were measured in at least 95.7% of infants, except for serotypes 1 (90.5%) and 6B (84.5%). In addition, all the infants in the PHiD-CV group were seroprotected against diphtheria, tetanus, Hib, and hepatitis B or seropositive for antibodies against pertussis and NTHi protein D (except one infant). Incidences of solicited local and general symptoms were comparable between groups, except for fever (axillary temperature ≥ 37.5°C), which seemed to occur more frequently in the PHiD-CV group. In conclusion, PHiD-CV was shown to be immunogenic and well-tolerated when co-administered with DTPw-HBV/Hib in Indian infants.