Prevention of rotavirus gastroenteritis in infants and children: rotavirus vaccine safety, efficacy, and potential impact of vaccines

Rotavirus infection is the most common cause of severe gastroenteritis globally, with greater than 86% of deaths occurring in low-income and middle-income countries. There are two rotavirus vaccines currently licensed in the United States and prequalified by the World Health Organization. RV1 is a monovalent attenuated human rotavirus strain, given orally in two doses. RV5 is a pentavalent human-bovine reassortant rotavirus vaccine, given orally in three doses. A third rotavirus vaccine, LLV, is a lamb rotavirus strain given orally as a single dose, which is currently available only in China. RV1 and RV5 have been shown to be highly efficacious in developed countries, and initial results from trials in Africa and Asia are promising as well. At least three other vaccines are in development, which are being developed by manufacturers of developing countries. Further studies are needed to clarify issues including administration of oral rotavirus vaccines with breastfeeding and other oral vaccines, and alterations in dosing schedule. Using new data on global diarrheal burden, rotavirus is estimated to cause 390,000 deaths in children younger than 5 years. Should rotavirus vaccines be introduced in the routine immunization programs of all countries, a potential of 170,000 deaths could be prevented annually. The largest impact on mortality would be seen in low-income and middle-income countries, despite poor immunization coverage and lower efficacy. Therefore, international efforts are needed to ensure that rotavirus vaccines reach the populations with highest burden of rotavirus disease

Feasibility of Concomitant Boost using Conformal Technique in Locally Advanced Carcinoma Uterine Cervix

AIM OF THE STUDY : To evaluate the feasibility and efficacy of concomitant boost using 3D-CRT in patients with locally advanced cervical cancer. MATERIALS AND METHODS : This is a prospective study of 29 patients with locally advanced FIGO Stage III.B who were treated with Concomitant boost using conformal technique. External beam radiotherapy TD 49.4 Gy was delivered to the whole pelvis(apart from the primary GTV) along with a concomitant boost to the primary GTV TD 54.6 Gy concurrent with weekly CDDP (40mg/m2) followed by intracavitary brachytherapy. Treatment planning was done with forward planning conformal therapy using field in field technique based on the recommendations of ICRU 83. Treatment related morbidity was assessed based on the CTCAE ver 4.0 and RTOG grading of acute toxicity. A repeat CT and re plan was done at 36 Gy. A volumetric assessment of tumour shrinkage was assessed based on RECIST criteria and clinical response was assessed at 30 Gy, 50 Gy and at follow up. RESULTS : Among 29 patients who received concomitant boost radiotherapy, 18 patients (62.06%) tolerated radiotherapy well without radiation related morbidity. Grade I/II proctitis was seen in 5 patients (17.2%). 1 patient (3.4%) developed Grade II Nausea and vomiting. 2 patients (6.89%) developed Grade I skin reaction and 3 patients (10.3%) developed Grade I Diarrhea. Chemotherapy was delivered to 18 patients of whom only 8 patients (44.4%) completed the complete course of chemotherapy. Among the patients who received chemotherapy, 5 patients (27.7%) tolerated chemo well without any acute morbidity and 3 patients developed Grade III acute morbidity which required radiotherapy to be pended. 6 patients (33.3%) developed Grade I/II CINV. Grade I/II neutropenia was seen in 2 patients (11.1%) and Grade III Neutropenia was seen in 2 patients (11.1%). 7 patients (38.8%) developed Grade I/II Hypokalemia,. 1 patient (5.5%) developed Grade III Hyponatremia and 1 patient (5.5%) developed Grade 1 Hyponatremia. In this analysis, 1 patient (5.5%) had Cisplatin induced Sensory neural hearing loss and 1 patient (5.5%) had Hypomagnesemia. 11 Patients (37.9%) had treatment breaks of more than 10 days of whom 9 patients received chemotherapy but none of the treatment breaks were related to toxicity. After completion of treatment, patients were reassessed after 6 weeks. 21 patients (72.41%) had a complete response and 8 patients (27.5%) had residual or progressive disease. All 8 patients had local failure, of which 2 patients also had distant metastasis (para-aortic node / SCL node). CONCLUSION : Concomitant boost using conformal technique is feasible in locally advanced cervical cancer with acceptable toxicity profile. The patients enrolled in this study were locally advanced Stage III.B with bulky disease. Although the local response rates with concomitant boost appears to be satisfactory, long term follow up and further randomized studies with standard chemoradiation is necessary before coming to any conclusion

Practices of Rural Egyptian Birth Attendants During the Antenatal, Intrapartum and Early Neonatal Periods

Neonatal deaths account for almost two-thirds of infant mortality worldwide; most deaths are preventable. Two-thirds of neonatal deaths occur during the first week of life, usually at home. While previous Egyptian studies have identified provider practices contributing to maternal mortality, none has focused on neonatal care. A survey of reported practices of birth attendants was administered. Chi-square tests were used for measuring the statistical significance of inter-regional differences. In total, 217 recently-delivered mothers in rural areas of three governorates were interviewed about antenatal, intrapartum and postnatal care they received. This study identified antenatal advice of birth attendants to mothers about neonatal care and routine intrapartum and postpartum practices. While mothers usually received antenatal care from physicians, traditional birth attendants (dayas) conducted most deliveries. Advice was rare, except for breastfeeding. Routine practices included hand-washing by attendants, sterile cord-cutting, prompt wrapping of newborns, and postnatal home visits. Suboptimal practices included lack of disinfection of delivery instruments, unhygienic cord care, lack of weighing of newborns, and lack of administration of eye prophylaxis or vitamin K. One-third of complicated deliveries occurred at home, commonly attended by relatives, and the umbilical cord was frequently pulled to hasten delivery of the placenta. In facilities, mothers reported frequent use of forceps, and asphyxiated neonates were often hung upside-down during resuscitation. Consequently, high rates of birth injuries were reported. Priority areas for behaviour change and future research to improve neonatal health outcomes were identified, specific to type of provider (physician, nurse, or daya) and regional variations in practices

Emerging infectious diseases among indigenous peoples

Many indigenous peoples are at higher risk for emerging infectious diseases compared to other populations. This conference panel focused on diseases of particular concern to Native Americans (American Indians and Alaska Natives), Australian aboriginal peoples, and the Maori of New Zealand. Important emerging diseases among these groups include respiratory tract infections, infections with antimicrobial-resistant organisms, zoonotic diseases, viral hepatitis, Helicobacter pylori and respiratory syncytial virus infections, diseases caused by Group A and B streptococcus, tuberculosis, and bacteremia and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis. Although the populations discussed are diverse, they have many things in common, including a high risk for many emerging infectious diseases, the requirement for culturally appropriate prevention and control strategies, and the need for increased leadership within communities of indigenous peoples

Efficacy of a pentavalent rotavirus vaccine in reducing rotavirus-associated health care utilization across three regions (11 countries)

OBJECTIVE: To evaluate the effect of a human-bovine reassortant pentavalent rotavirus vaccine (PRV) on health care encounters in nearly 70 000 subjects randomized in three regions - Europe, the United States, and Latin America/the Caribbean - in the Rotavirus Efficacy and Safety Trial (REST). METHODS: Healthy 6- to 12-week-old infants received 3 doses of PRV or placebo at 4- to 10-week intervals. The exact binomial method for ratios of Poisson counts was used to evaluate the effect of PRV on the rate of rotavirus-related hospitalizations and emergency department (ED) visits involving rotavirus G-types 1-4 occurring > or =14 days after the third dose of vaccine for up to 2 years. RESULTS: In fully vaccinated infants, reductions in rotavirus-associated hospitalizations and ED visits were 94.7% (95% CI: 90.9, 96.9) in Europe, 94.9% (95% CI: 84.0, 98.9) in the United States, and 90.0% (95% CI: 29.4, 99.8) in the Latin American/Caribbean regions. CONCLUSIONS: PRV reduced hospitalizations and ED visits within each region in REST. Results were consistent across regions and across the overall study cohort

Oral rehydration versus intravenous therapy for treating dehydration due to gastroenteritis in children: a meta-analysis of randomised controlled trials

BACKGROUND: Despite treatment recommendations from various organizations, oral rehydration therapy (ORT) continues to be underused, particularly by physicians in high-income countries. We conducted a systematic review of randomised controlled trials (RCTs) to compare ORT and intravenous therapy (IVT) for the treatment of dehydration secondary to acute gastroenteritis in children. METHODS: RCTs were identified through MEDLINE, EMBASE, CENTRAL, authors and references of included trials, pharmaceutical companies, and relevant organizations. Screening and inclusion were performed independently by two reviewers in order to identify randomised or quasi-randomised controlled trials comparing ORT and IVT in children with acute diarrhea and dehydration. Two reviewers independently assessed study quality using the Jadad scale and allocation concealment. Data were extracted by one reviewer and checked by a second. The primary outcome measure was failure of rehydration. We analyzed data using standard meta-analytic techniques. RESULTS: The quality of the 14 included trials ranged from 0 to 3 (Jadad score); allocation concealment was unclear in all but one study. Using a random effects model, there was no significant difference in treatment failures (risk difference [RD] 3%; 95% confidence intervals [CI]: 0, 6). The Mantel-Haenzsel fixed effects model gave a significant difference between treatment groups (RD 4%; 95% CI: 2, 5) favoring IVT. Based on the four studies that reported deaths, there were six in the IVT groups and two in ORT. There were no significant differences in total fluid intake at six and 24 hours, weight gain, duration of diarrhea, or hypo/hypernatremia. Length of stay was significantly shorter for the ORT group (weighted mean difference [WMD] -1.2 days; 95% CI: -2.4,-0.02). Phlebitis occurred significantly more often with IVT (number needed to treat [NNT] 33; 95% CI: 25,100); paralytic ileus occurred more often with ORT (NNT 33; 95% CI: 20,100). These results may not be generalizable to children with persistent vomiting. CONCLUSION: There were no clinically important differences between ORT and IVT in terms of efficacy and safety. For every 25 children (95% CI: 20, 50) treated with ORT, one would fail and require IVT. The results support existing practice guidelines recommending ORT as the first course of treatment in appropriate children with dehydration secondary to gastroenteritis

Acceptability of Massage with Skin Barrier-enhancing Emollients in Young Neonates in Bangladesh

Oil massage of newborns has been practised for generations in the Indian sub-continent; however, oils may vary from potentially beneficial, e.g. sunflower seed oil, to potentially toxic, e.g. mustard oil. The study was carried out to gain insights into oil-massage practices and acceptability of skin barrier-enhancing emollients in young, preterm Bangladeshi neonates. Preterm infants of <33 weeks gestational age were randomized to high-linoleate sunflower seed oil, Aquaphor Original Emollient Ointment™, or the comparison group (usual care). A survey was administered at admission to assess routine skin-care practices prior to admission and at discharge to assess acceptability of emollient therapy during hospitalization. Oil massage was given to 83 (21%) of 405 babies before hospital admission, 86% (71/83) of whom were delivered at home. Application of oil, most commonly mustard oil (88%, 73/83), was started within one hour of birth in 51 cases (61%) and was applied all over the body (89%, 74/83) one to six (mean 2.2) times before admission. Of infants who received emollient therapy in the hospital, 42% (n=32) of mothers reported that the emollient applied in the hospital was better than that available at home, and only 29% would use the same oil (i.e. mustard oil) in the future as used previously at home. No problems resulted from use of emollient in the hospital. Topical therapy with sunflower seed oil or Aquaphor was perceived by many families to be superior to mustard oil. If caregivers and health professionals can be motivated to use inexpensive, available emollients, such as sunflower seed oil that are beneficial, emollient therapy could have substantial public-health benefit

Gender Differences in Perception and Care-seeking for Illness of Newborns in Rural Uttar Pradesh, India

Although gender-based health disparities are prevalent in India, very little data are available on care-seeking patterns for newborns. In total, 255 mothers were prospectively interviewed about their perceptions and action surrounding the health of their newborns in rural Uttar Pradesh, India. Perception of illness was significantly lower in incidence (adjusted odds ratio=0.56, 95% confidence interval 0.33-0.94) among households with female versus male newborns. While the overall use of healthcare providers was similar across gender, the average expenditure for healthcare during the neonatal period was nearly four-fold higher in households with males (Rs 243.3±537.2) compared to females (Rs 65.7±100.7) (p=0.07). Households with female newborns used cheaper public care providers whereas those with males preferred to use private unqualified providers perceived to deliver more satisfactory care. These results suggest that, during the neonatal period, care-seeking for girls is neglected compared to boys, laying a foundation for programmes and further research to address gender differences in neonatal health in India

Determining Gestational Age in a Low-resource Setting: Validity of Last Menstrual Period

The validity of three methods (last menstrual period [LPM], Ballard and Dubowitz scores) for assessment of gestational age for premature infants in a low-resource setting was assessed, using antenatal ultrasound as the gold standard. It was hypothesized that LMP and other methods would perform similarly in determining postnatal gestational age. Concordance analysis was applied to data on 355 neonates of <33 weeks gestational age enrolled in a topical skin-therapy trial in a tertiary-care children's hospital in Bangladesh. The concordance coefficient for LMP, Ballard, and Dubowitz was 0.878, 0.914, and 0.886 respectively. LMP and Ballard underestimated gestational age by one day (±11) and 2.9 days (±7.8) respectively while Dubowitz overestimated gestational age by 3.9 days (±7.1) compared to ultrasound finding. LMP in a low-resource setting was a more reliable measure of gestational age than previously thought for estimation of postnatal gestational age of preterm infants. Ballard and Dubowitz scores are slightly more reliable but require more technical skills to perform. Additional prospective trials are warranted to examine LMP against antenatal ultrasound for primary assessment of neonatal gestational age in other low-resource settings

Nanomedicine: towards development of patient-friendly drug-delivery systems for oncological applications

The focus on nanotechnology in cancer treatment and diagnosis has intensified due to the serious side effects caused by anticancer agents as a result of their cytotoxic actions on normal cells. This nonspecific action of chemotherapy has awakened a need for formulations capable of definitive targeting with enhanced tumor-killing. Nanooncology, the application of nanobiotechnology to the management of cancer, is currently the most important area of nanomedicine. Currently several nanomaterial-based drug-delivery systems are in vogue and several others are in various stages of development. Tumor-targeted drug-delivery systems are envisioned as magic bullets for cancer therapy and several groups are working globally for development of robust systems