, 1998) Activation of these receptors in the hippocampus also ex

, 1998). Activation of these receptors in the hippocampus also exerts negative feedback on the HPA axis, suppressing further

release of glucocorticoids following stress termination, thus inappropriate functioning of the hippocampus could disrupt proper functioning of the HPA axis (De Kloet et al., 1998). In addition to playing a key role in the regulation of stress response, the hippocampus is also particularly vulnerable to the effects of stress (McEwen and Sapolsky, 1995, McEwen et al., SP600125 cost 1992 and Sapolsky, 1986). Plasma concentrations of cortisol are increased in depressed adults (Westrin et al., 1999) and it has been suggested that elevated glucocorticoid concentrations contribute to stress-induced atrophy of the hippocampus (McEwen and Sapolsky, 1995) and its correlation with cognitive dysfunction (Lupien et al., 1998). Accordingly, neuroimaging studies report volumetric reductions in the hippocampus in depression (Bremner et al., 2000, Frodl et al., 2002, Sheline et al., 1996 and Videbech and Ravnkilde, Selleck PI3K inhibitor 2004) and that these volumetric reductions seem to be more apparent in unmedicated depressed individuals (Sheline et al., 2003) and in poor responders to antidepressant treatments

(Frodl et al., 2008). Similarly, volumetric reductions in the hippocampus have also been reported in PTSD patients (Felmingham et al., Carnitine dehydrogenase 2009, Smith, 2005 and Bremner et al., 2003) and PTSD patients exhibit dysfunction of the HPA-axis with high levels of corticotropin-releasing hormone in the cerebrospinal fluid (Bremner et al., 1997) and low levels of cortisol in urine (Yehuda et al., 1995), indicating an enhanced HPA-axis feedback regulation (de Kloet et al., 2006). Taken together, it is clear that there is a reciprocal

relationship between the hippocampus and glucocorticoids and that disrupted HPA-axis activity might impact hippocampal structure and function which in turn might further impact hippocampal regulation of glucocorticoid concentrations. In addition to its role in regulating the HPA axis, the hippocampus is a rather unique structure in that it is one of just a few areas in the healthy mammalian brain where neurogenesis, the birth of new neurons, occurs throughout adult life (Kempermann et al., 2004 and Ming and Song, 2011). Adult hippocampal neurogenesis occurs in the subgranular zone of the hippocampus and is comprised of several stages: cell proliferation, neuronal differentiation and survival, and maturation of the newly-born neurons (Christie and Cameron, 2006) (see Fig. 1). It is now well established that adult hippocampal neurogenesis is sensitive to a number of extrinsic factors including stress, antidepressant treatment and environmental experience (Schloesser et al.

Group G-D was inoculated with 107 C6/36 derived RVFV Group G-E w

Group G-D was inoculated with 107 C6/36 derived RVFV. Group G-E was inoculated with 105 PFU of Vero E6 RVFV stock, and re-inoculated IV with the same inoculum at 1 dpi. Group G-F was inoculated with 105 PFU of C6/36 derived RVFV, and re-inoculated

IV with the same inoculum at 1 dpi. Group G-G was inoculated with 107 C6/36 derived RVFV and re-inoculated SC with the same inoculum at 1 dpi. All goats were kept for four weeks following the inoculation to monitor an antibody development. Serum samples collected at 0, 4, 5, 6, 7, 14, 21 and 28–30 dpi were analyzed for presence of neutralizing antibodies. Differences in susceptibility to RVFV infections were observed between sheep and goats, and also between breeds of sheep. In the first study,

conducted BKM120 in Suffolk-cross sheep, all animals developed viremia at 3 dpi, both by virus isolation and RNA detection when inoculated with 105 PFU of virus produced in Vero cells. However, when the Rideau Arcott cross lambs were inoculated via the same route and the same inoculum, only three out of four animals had detectable RVFV RNA in their blood and only two developed viremia (Fig. 1). Subsequently different inoculation approaches were tested to obtain a more reliable viremia model. Genomic sequences of the inocula were verified prior to the start of the animal inoculations. Concurrently with the infection experiments, characterization on protein level of RVFV 17-AAG generated in Vero E6 cells or the C6/36 was taking place. There was no difference in genome of RVFV generated in Vero E6 cells

compared to virus generated in C6/36 cells, including the stock viruses used in experimental PDK4 inoculations, and the sequences corresponded with sequences published for RVFV ZH501 in Gen Bank. Both viruses had functional NSm and NSs coding genes, as immunoblots of infected cell lysates indicated that all proteins from the M and S segments were expressed. The viruses however differed in protein composition of virions, with the mosquito-cell generated RVFV having an additional large glycoprotein (78 kDa) incorporated into virions [23]. Subcutanous inoculation was used in all primary inoculation. Two doses (105 or 107 PFU/animal) and two different inocula (prepared either in Vero E6 or in C6/36 cells) were tested. The titer of inoculum was confirmed by back-titration at the time of inoculation, and stayed within 0.5 log10 difference from the targeted dose. In specific groups, attempts were made to increase the viremia by re-inoculation, either by the subcutaneous or by the intravenous route at 1 dpi. A summary of the experimental groups is presented in Table 1. Using the same mode of inoculation as for the Suffolk breed (group S-A), the 105 PFU dose of Vero E6 produced RVFV in Rideau Arcott cross lambs (group S-B) lead to development of viremia only in three out of four animals at 2 dpi.

We found that 4 weeks of serial night casting resulted in statist

We found that 4 weeks of serial night casting resulted in statistically significant but small increases in ankle dorsiflexion range

compared with no intervention. However, these effects were not maintained with stretching at 8 weeks. This does not mean we should abandon stretching interventions in children and young adults with Charcot-Marie-Tooth disease. We found serial night casting to be safe and well tolerated. Many of the participants selleck chemical commented that the intervention was worthwhile and continued to wear the casts after they had completed the study. Participants also appreciated having to wear the casts only at night, as they could participate in their regular daytime activities and avoid feeling self-conscious about wearing serial casts to school, university, or work. Further Duvelisib in vitro investigation into the efficacy of serial night casting for children and young adults with Charcot-Marie-Tooth disease is required.

Such studies should be designed to allow for a greater number of cast changes, to control for leg position while sleeping and be conducted over a longer period of time in order to assess the effect of the intervention on functional and meaningful outcomes such as walking distance, fatigue, balance, pain, and activity participation. eAddenda: Table 3 available at jop.physiotherapy.asn.au Ethics: The Human Research and Ethics Committee of The Children’s Hospital at Westmead, Australia, approved this study. Informed consent was obtained for all participants before data collection began. Competing interests: None declared. Support: KJR is supported by a scholarship from the Medical Foundation of The University of Sydney and JB is supported by an Australian Clinical Research Fellowship from the National Health and Medical Research Council of Australia (NHMRC#336705). Grant obtained from the Australian

Podiatry Education and Research Foundation Research. We thank Stephanie Wicks for study co-ordination, Annie Soo for participant randomisation, and Roger Adams for statistical advice. “
“The combination of much physiological ageing, physical inactivity, and the additional burden of a number of pathological disease processes often culminates in disability which may manifest as an inability to live independently or to participate fully in community life. Hospital admission for an acute medical or surgical problem in an older person may be accompanied by a persistent decline in both physical and cognitive functioning. In some people this decline leads to a loss of independence (Kortebein 2009) and in many people to a loss of the ability to complete more difficult mobility tasks.

for C21H25N3O4: C, 65 78; H, 6 57; N, 10 96; O, 16 69 Found: C,

for C21H25N3O4: C, 65.78; H, 6.57; N, 10.96; O, 16.69. Found: C, 65.91; H, 6.35; N, 11.07. Yellow gummy solid, 1H NMR (400 MHz, CDCl3): δ 2.33 (s, 3H), 2.68 (brs, 4H), 3.04 (brs, 4H), 3.66 (s, 2H), 3.77 (s, 3H) 3.88 (s, 3H), 6.91–6.93 (m, 1H), 7.09–7.14 (m, 2H), 8.21 (s, 1H). 13C NMR (100 MHz, CDCl3): δ (ppm) 164.02, 156.19, 151.42, 148.6, 133.94, 127.43, 127.35, 126.09, 125.00, Dabrafenib mw 124.34, 118.54, 62.68, 59.83, 53.32, 51.30, 13.24, 11.00; MS (e/z): 379,

381 (M−, M+). Anal. calcd. for C19H23Cl2N3O: C, 60.00; H, 6.10; Cl, 18.64; N, 11.05; O, 4.21. Found: C, 60.11; H, 6.05; N, 11.15. Pale yellow gummy solid, Mass (e/z): 1H NMR (400 MHz, CDCl3): δ 2.06–2.27 (m, 2H), 2.27 (s, 3H), 2.69 (brs, 4H), 3.05 (brs, 4H), 3.36 (s, 3H), 3.58 (m, 2H), BEZ235 datasheet 4.10 (t, 3H), 6.69 (d J = 5.6 Hz, 2H), 6.91–6.93 (m, 1H), 7.09–7.14 (m, 2H), 8.30 (s, 1H). 13C NMR (100 MHz, CDCl3): δ (ppm) 163.01, 157.09, 151.82, 149.6, 134.25, 128.42, 127.43, 126.28, 125.12, 124.45, 118.65, 77.53, 71.42, 64.51, 62.82, 59.94, 53.45, 51.41, 11.28; MS (e/z): 423, 425 (M−, M+). Anal. calcd. for C21H27Cl2N3O2: C, 59.44; H, 6.41; Cl, 16.71; N, 9.90; O, 7.54. Found: C, 59.56; H, 6.34; N, 9.98. Light brown colour syrup. 1H NMR (400 MHz, CDCl3): δ 2.32 (s, 3H), 2.69 (brs, 4H), 3.05 (brs, 4H), 3.73 (s, 2H), 4.36–4.4.42 (q = 3H), 6.64 (d, J = 8 Hz, 1H), 6.91–6.93 (m, 1H), 7.01–7.05 (m, 4H), 8.36 (d, J = 5.6 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ (ppm) 163.13, 157.18,

151.91, 149.62, 134.31, 128.52, 127.32, 126.34, 125.21, 124.52, 122.12, 118.72, 85.72, 62.99, 60.08, 53.65, 51.61, 11.45; Mass (e/z): 433, 435 (M−, M+). Anal. calcd. for C19H20Cl2F3N3O: C, 52.55; H, 4.64; Cl, 16.33; F, 13.12; N, 9.68; O, 3.68. Found: C, 52.66; H, 4.57; N, 9.78. Pale yellow colour syrup. 1H NMR (400 MHz, CDCl3): δ 2.76 (brs, 4H), 3.07 (brs, 4H), 3.77 (s, 2H), 3.77 (s, 3H) 3.88 (s, 3H), 6.81 (d, J = 7.6 Hz, Unoprostone 1H), 6.92–6.94 (m, 1H), 7.01–7.14 (m, 2H), 8.27 (d, J = 5.6 Hz, 1H). ); 13C NMR (100 MHz, CDCl3): δ (ppm) 158.6, 151.3, 145.6, 127.4, 124.3, 118.5, 106.7, 77.5, 77.17, 76.8, 61.08, 58.12, 55.61, 53.27, 51.13; MS (e/z): 381, 383 (M−, M+).


For all constructs, the vector induced T cell respon


For all constructs, the vector induced T cell responses decreased with time following immunization. Similar results were seen by intracellular cytokine staining assays (data not presented). Responses were primarily mediated by CD8+ T cells, not CD4+ T cells (data not presented). Serum IgG antibody titers induced by immunization with the various AMA1 adenovectors were measured by ELISA and compared against antibodies produced to a recombinant Pichia pastoris produced glycosylated AMA1 protein (residues 25–546) [40] as a reference standard ( Fig. 3b). Antibody check details responses were observed 2 weeks following the first adenovector administration for all cell surface associated forms of AMA1, and these responses were effectively boosted by a second administration of adenovector. The adenovector that expressed an intracellular form of AMA1, AMA1-IC, did not induce AMA1-specific serum antibody responses. Adenovector-induced antibody responses were also evaluated in rabbits. Two immunizations of adenovector were administered at an 8-week interval and AMA1-specific serum antibodies were measured 4 weeks after the second dose. AMA1-IC was not included in this analysis as it was a poor inducer of antibody responses

in the murine studies. The results with rabbit sera were similar to those from the murine studies. Specifically, the native glycosylated AMA1 and both glycosylation mutants GM1 and GM2 NVP-AUY922 induced comparable levels of

AMA1-specific serum antibody, with the highest responses induced by adenovectors that expressed native AMA1 and the AMA1-GM2 antigens (Fig. 3c). Since ELISA assays do not provide information on the biological function of antibodies, the ability of the adenovectors to induce functional antibodies capable of inhibiting the invasion of erythrocytes by blood stage forms of P. falciparum was evaluated, using a standardized and highly reproducible parasite GIA [41]. Initially, GIA was performed ADAMTS5 using a final concentration of 2.5 mg/ml of purified IgG from immunized rabbits. This concentration of IgG is approximately one-quarter of that in human blood. Previous results from other experiments in rabbits, also performed at the GIA Reference Center utilizing the same assay and standardized operating procedures, yielded approximately 90% inhibition of parasite growth following immunization with recombinant AMA1 protein (80 mg) formulated in alum +CpG or ISA720. Very high titers of functional antibodies were induced in rabbits by the adenovectors expressing AMA1. Greater than 99% inhibition was achieved following vaccination with AdAMA1 in this standard assay. The native and GM2 versions of AMA1 induced equally high levels of functional antibodies ( Fig. 4a) and total antibody by ELISA ( Fig. 4b).

1 To address this question, the breadth and magnitude of the ant

1. To address this question, the breadth and magnitude of the antibody response to all regions of Msp2 were compared PD0325901 chemical structure in immunized animals and non-immunized, infected animals at the time of control of the initial bacteremia. Regardless of the treatment, the breadth scores to the HVR peptides were higher than the CR peptides (Fig. 2a). For example, the immunized animals had a mean breadth score of 0.19 ± 0.12 for the CR peptides and a score of 0.67 ± 0.15 for the HVR peptides; while the infected animals had a breadth

score of 0.15 ± 0.06 for the CR peptides and 0.71 ± 0.14 for the HVR peptides. The breadth scores to the CR peptides were slightly higher in the immunized animals (0.19 ± 0.12) than in the infected animals (0.15 ± 0.06). However, these differences were not statistically significant and are unlikely to be biologically relevant, as they predominantly represent differences between individual animals, and are due to the recognition of three additional CR peptides, P3, P15, and P14. P3 and P15 were recognized by vaccinee 5933. Although this animal had the highest breadth score (0.40) for the CR peptides, it also had the second highest bacteremia (4.5% infected erythrocytes) of the immunized animals

(Table 3). P14 was solely recognized by vaccinee 5952. The breadth scores RG7420 nmr to the HVR peptides were similar when comparing the immunized and infected animals, with the scores in the infected animals marginally higher (Fig. 2a). When comparing titers, the immunized animals had higher titers to the CR of Msp2 than did the infected animals (Fig. 2b). However, the difference was not statistically significant and was attributed to the variation among individual Astemizole animals. The infected cattle had higher titers to the HVR than did the vaccinees, however, this was primarily attributed an animal (5967) with markedly high titers. Similarly, there were no significant differences between the immunized and infected animals when evaluating the titers to individual peptides (Supplemental Fig. 1). Due to the wide variation among individuals within a group, we posed the following question: within a treatment group, is there a correlation

between the control of bacteremia and the breadth or magnitude of the anti-Msp2 antibody response? Among the animals that were infected, there was no correlation between the breadth scores to either the CR or HVR peptides and bacteremia (Fig. 3). For example, one of the animals (5969) with the highest total breadth (including both the HVR and CR) score also had the highest bacteremia (31%). In contrast, there was a strong inverse correlation between bacteremia and titers to the CR (Fig. 4a), but not the HVR (Fig. 4b), of Msp2. Those animals with higher titers to the CR had lower levels of bacteremia (Spearman rank correlation coefficient = −0.97, p ≤ 0.005). To address this question, only the immunized animals were considered.

Cells were maintained in minimal essential medium (MEM) supplemen

Cells were maintained in minimal essential medium (MEM) supplemented with 10% fetal bovine serum (FBS) and 0.01% antibiotic–antimycotic solution, trypsin–EDTA. All other chemicals were of reagent grade. 4-methyl pyrimido (5, 4-c) quinoline- 2, 5 (1H, 6H)-dione (Fig. 2) was synthesized in the Department of Chemistry, Bharathiar University and it was dissolved in phosphate-buffered PARP inhibitor saline (PBS) and diluted to concentrations ranging from 10 to 100 μM (MW- 227). The viruses (10−5.1TCID50/mL [Tissue culture infectious dose]) were added to 4-methyl pyrimido (5, 4-c) quinoline-2,5(1H, 6H)-dione solutions of different concentration and maintained at 4 °C for a pre-determined period of time. Following the treatment,

the virus titer in the mixture was measured by inoculating serial dilutions (10−1–10−6) of the mixture into the host cells. The (TCID50) was calculated by the Behrens–Karber’s method based on the cytopathic effect. The cytotoxicity Selleckchem Enzalutamide of 4-methyl pyrimido (5, 4-c) quinoline-2,5(1H, 6H)-dione on the cultured MDCK cells were analyzed by measuring the MTT 3- (4,5-dimethylthiozol-2-yl)-3, 5-dipheryl tetrazolium bromide (Hi-Media). The percentage of cytotoxicity was calculated by the following

equation using the obtained absorbance values, from which the absorbance values in the corresponding control. %ofproliferation=Abs620(Treated)Abs620(Untreatedcells)×100 The hemagglutination (HA) titer of the influenza A/H1N1 (2009) virus was measured in 96-well microplates (Nunc, USA) with U-shaped bottom. The virus was serially diluted in a two-fold dilution with PBS. Into each well containing 100 μl of the virus solution, an equal volume of 0.9% guinea pig erythrocytes suspended in PBS was added. Following mechanical vibration, the plates containing the mixture of virus and erythrocytes were kept at room temperature, and the results were recorded after 30 min.

The titer was expressed as the reciprocal of the highest dilution of the virus showing complete HA. The assay was triplicate for each virus dilution, and the HA titer determined represents the titer identically recorded with Parvulin all of the three or two out of the three tests. We considered the difference greater than 2 times to be a significant difference in HA titer. Confluent monolayer of MDCK cells in 12-well plates were washed once with phosphate-buffered saline (PBS) and then infected with influenza virus at 0.1 multiplicity of infection (MOI). The plates were continuously shaker for 45 min at room temperature in compound-free conditions for virus adsorption. The solution was removed and replaced with MEM medium containing synthesized compound of various concentrations. Viruses were harvested at 8, 24, 36 h post-infection, and the viral yield was estimated by plaque assay on MDCK cells. As a control, the infected cells incubated in test compound-free medium were included throughout the experiment. MDCK cells were grown at about 80% confluence and infected with influenza virus at 0.

The intra-day precision (%RSD) was assessed by analysing standard

The intra-day precision (%RSD) was assessed by analysing standard drug solutions within the calibration range, three times on the

same day. Inter-day precision (%RSD) was assessed by analysing drug solutions within the calibration range on three different days over a period of a week. In order to determine detection and quantification limit, concentrations in the lower part of the linear range of the calibration curve were used. Stock solution of TDF and ETB learn more was prepared and different volume of stock solution in the range 150–300 ng for TDF and 100–200 ng for ETB were spotted in triplicate. The amount of both the drugs by spot versus average response (peak area) was graphed and the equation for this was determined. The standard deviations (S.D.) of responses were calculated. The average of standard deviations was calculated (A.S.D.). Detection limit was calculated by (3.3 × A.S.D.)/b and quantification limit was calculated by (10 × A.S.D.)/b, where “b” corresponds to the slope obtained in the linearity study of method. Specificity of the method was ascertained by analysing standard drug and sample. The mobile phase resolved both the drugs very efficiently, as shown in (Fig. 2). The spot for TDF and ETB was confirmed by comparing the Rf and spectra of the spot with that of standard. The peak

Panobinostat molecular weight purity of TDF and ETB was assessed by comparing the spectra at three different levels, i.e. peak start (S), peak apex (M) and peak end (E) positions of the spot. Recovery study was carried out by over spotting 80%, 100% and

120% of the standard drug solution of TDF and ETB and the mixtures were reanalysed by the proposed method. The experiment was conducted in triplicate. This was done to check the recovery of the drug enough at different levels in formulation. Robustness was studied in six replicate at the concentration level of 450 ng/spot for TDF and 300 ng/spot for ETB. In this study, seven parameters (mobile phase composition, mobile phase volume, development distance, relative humidity, duration of saturation, time from spotting to chromatography and chromatography to spotting) were studied and the effects on the results were examined. The ruggedness of the proposed method was evaluated by two different analysts. To determine the content of TDF and ETB simultaneously in conventional tablets (label claim 300 mg TDF and 200 mg ETB); twenty tablets were accurately weighed, average weight determined and ground to a fine powder. A quantity of powder equivalent to 150 mg TDF and 100 mg of ETB was transferred into 100 ml volumetric flask containing 50 ml methanol, sonicated for 30 min and diluted to mark with same solvent. The resulting solution was filtered using 0.45 μm filter (Millifilter, MA). 0.4 μL of the above solution applied on TLC plate followed by development and scanning as described in Section 2.2.

The dried extract was dissolved in respective solvents prior to a

The dried extract was dissolved in respective solvents prior to assay. The total phenolic content (mg of catechin/1 mg) was determined

using Folin–Ciocalteu reagent5 and total flavonoid content (catechol equivalents/1 mg) was determined by aluminium chloride method.6 The reductive ability of the extracts was determined by potassium ferricyanide reduction method.7 The hydrogen or electron donation ability of the plant extracts was measured from bleaching of the purple colour of DPPH.8 Scavenging activity of extracts on superoxide anion radicals was determined based on the reduction of nitroblue tetrazolium (NBT).9 Hydroxyl radical scavenging and the ferrous ion-chelating potential of the extracts were measured following deoxyribose assay10 and ferrozine assay11 respectively. Thiobarbituric acid reactive substance assay Selleck Adriamycin was employed Selleckchem INK128 to determine anti-lipid peroxidation assay using goat liver homogenate.12 All analyses were carried

out in triplicates. Data were presented as mean ± SD. Radical scavenging activity of extracts was expressed in terms of percentage of inhibition. DPPH, superoxide radical scavenging, hydroxyl radical scavenging and metal ion-chelating assay were calculated using the following equation: % Inhibition = (Absorbance of control − Absorbance of sample)/Absorbance of control × 100, and the anti-lipid peroxidation percentage was calculated using the formula: % ALP = (Absorbance of Fe2+ induced peroxidation-Absorbance of sample)/Absorbance of Fe2+ induced peroxidation-Absorbance of control × 100. The IC50 value was determined using Easy Plot software. The total phenolic contents of aqueous and methanolic extracts of A. solanacea leaves were 0.030 ± 0.01 and 0.040 ± 0.02 mg of catechin equivalents/1 mg dried extract respectively and the corresponding flavonoid contents were 0.257 ± 0.02 and 0.404 ± 0.03 mg of catechol equivalents/1 mg dried aqueous and methanolic extracts. Both the extracts showed powerful reducing power that increased linearly with concentration. The methanolic extract demonstrated powerful reduction

potential as compared to aqueous extract (Fig. 1). The IC50 values of methanolic and aqueous extracts for DPPH radical scavenging activity were 198.43 ± 1.30 SPTLC1 and 378.67 ± 2.5 μg/ml (Fig. 2) respectively which showed a marked difference with ascorbic acid standard (IC50 = 7.6 ± 0.20 μg/ml). The methanolic extract exhibited superoxide radical scavenging activity (Fig. 3) with an IC50 value of 1634. 97 ± 4.08 μg/ml and showed a significant difference when compared with butylated hydroxy anisole (IC50 value of 23.6 ± 0.86 μg/ml). The percentage inhibition of hydroxyl radical scavenging activity of the aqueous and methanolic extracts was found to be 62.81% and 92.89% respectively at 2000 μg/ml. Compared to all the other assays, at the lowest concentration (25 μg/ml) tested, the methanolic extract of A. solanacea was the one that showed higher (86.71%) free radical scavenging ability.

[17]) with 50% case-fatality, ∼65 deaths would occur by chance al

[17]) with 50% case-fatality, ∼65 deaths would occur by chance alone within a week of vaccination. Applying valid estimates of intussusception case-fatality selleck screening library from Africa will be useful for future benefit risk deliberations with regard to rotavirus vaccines. In summary, the recently published data on efficacy and impact of rotavirus vaccines from resource poor settings coupled with the high mortality of rotavirus disease in these settings provides stark

evidence of the need for rotavirus vaccines to improve child health in Africa. Emerging data from early introducer countries have also identified the possibility of a low level intussusception risk in some settings highlighting the need for scientifically sound safety monitoring data to better understand the benefit risk

ratio of rotavirus vaccination in developing countries. Thus, as these countries begin planning preparations for vaccine S3I-201 cost introduction, the WHO recommended that countries consider establishing disease surveillance systems to monitor the safety and effectiveness of these vaccines for measuring the full impact of rotavirus vaccines. However, the quality of post-marketing vaccine safety surveillance systems in African countries appears inadequate for detecting very rare adverse events such as intussusception. In addition, there is insufficient baseline data on the epidemiology and management of intussusception in Africa which is crucially needed for implementing surveillance systems. The lessons learned from this

Intussusception workshop address several of these gaps relevant for establishing intussusception surveillance. Attention should be directed towards larger “sentinel” paediatric hospitals with surgical services when implementing also surveillance systems for intussusception in Africa. Addressing confounding effects of age will be crucial for reliably determining whether a causal link exists between events identified through surveillance and rotavirus vaccine. And lastly, to make reliable interpretations of causality between rotavirus vaccine and intussusception, cases of intussusception presenting to the sentinel sites must be identified independent of the child’s vaccination status. If these conditions can be met and active sentinel surveillance for intussusception is established, the prospects are good for generating robust postlicensure safety monitoring data for rotavirus vaccines in Africa, thus allowing these countries to confidently undertake the WHO recommendations while ensuring the safety of rotavirus vaccines.