Aetiology and incidence of diarrhoea requiring hospitalisation in children under 5 years of age in 28 low-income and middle-income countries: findings from the Global Pediatric Diarrhea Surveillance network.

INTRODUCTION: Diarrhoea remains a leading cause of child morbidity and mortality. Systematically collected and analysed data on the aetiology of hospitalised diarrhoea in low-income and middle-income countries are needed to prioritise interventions. METHODS: We established the Global Pediatric Diarrhea Surveillance network, in which children under 5 years hospitalised with diarrhoea were enrolled at 33 sentinel surveillance hospitals in 28 low-income and middle-income countries. Randomly selected stool specimens were tested by quantitative PCR for 16 causes of diarrhoea. We estimated pathogen-specific attributable burdens of diarrhoeal hospitalisations and deaths. We incorporated country-level incidence to estimate the number of pathogen-specific deaths on a global scale. RESULTS: During 2017-2018, 29 502 diarrhoea hospitalisations were enrolled, of which 5465 were randomly selected and tested. Rotavirus was the leading cause of diarrhoea requiring hospitalisation (attributable fraction (AF) 33.3%; 95% CI 27.7 to 40.3), followed by Shigella (9.7%; 95% CI 7.7 to 11.6), norovirus (6.5%; 95% CI 5.4 to 7.6) and adenovirus 40/41 (5.5%; 95% CI 4.4 to 6.7). Rotavirus was the leading cause of hospitalised diarrhoea in all regions except the Americas, where the leading aetiologies were Shigella (19.2%; 95% CI 11.4 to 28.1) and norovirus (22.2%; 95% CI 17.5 to 27.9) in Central and South America, respectively. The proportion of hospitalisations attributable to rotavirus was approximately 50% lower in sites that had introduced rotavirus vaccine (AF 20.8%; 95% CI 18.0 to 24.1) compared with sites that had not (42.1%; 95% CI 33.2 to 53.4). Globally, we estimated 208 009 annual rotavirus-attributable deaths (95% CI 169 561 to 259 216), 62 853 Shigella-attributable deaths (95% CI 48 656 to 78 805), 36 922 adenovirus 40/41-attributable deaths (95% CI 28 469 to 46 672) and 35 914 norovirus-attributable deaths (95% CI 27 258 to 46 516). CONCLUSIONS: Despite the substantial impact of rotavirus vaccine introduction, rotavirus remained the leading cause of paediatric diarrhoea hospitalisations. Improving the efficacy and coverage of rotavirus vaccination and prioritising interventions against Shigella, norovirus and adenovirus could further reduce diarrhoea morbidity and mortality.

Epidemiology of intussusception in sub-Saharan Africa.

This supplement contains the findings from intussusception surveillance conducted in 9 countries. These articles provide information on the age distribution of intussusception in the first year of life with cases peaking at 4-6 months of age, highlight the high proportion of cases in most, but not all, countries that undergo surgery and often require bowel resection for the treatment of intussusception, and show the variability of treatment outcomes in different countries. These data will be important for improving diagnosis and treatment of intussusception in young children in sub-Saharan Africa.

Epidemiology of intussusception among infants in Ethiopia, 2013-2016.

INTRODUCTION: intussusception is a condition in which one segment of the bowel prolapses into another causing obstruction. Information on the epidemiology of intussusception in sub-Saharan Africa is limited. We describe the sociodemographic and clinical characteristics of children with intussusception in Ethiopia. METHODS: active surveillance for children < 12 months of age with intussusception was conducted at six sentinel hospitals in Ethiopia. Limited socio-economic and clinical data were collected from enrolled children. Characteristics among children who died and children who survived were compared using the Wilcoxon rank sum test for continuous variables and Chi-square tests for categorical variables. RESULTS: total of 164 children < 12 months of age with intussusception were enrolled; 62% were male. The median age at symptom onset was 6 months with only 12 (7%) of cases occurring in the first 3 months of life. Intussusception was reduced by surgery in 90% of cases and 10% were reduced by enema; 13% of cases died. Compared to survivors, children who died had a significantly longer time to presentation to the first health care facility and to the treating health care facility (median 3 days versus 2 days, p = 0.02, respectively). CONCLUSION: the high mortality rate, late presentation of intussusception cases, and lack of modalities for non-surgical management at some facilities highlight the need for better management of intussusception cases in Ethiopia.

Impact of rotavirus vaccine introduction and genotypic characteristics of rotavirus strains in children less than 5 years of age with gastroenteritis in Ethiopia: 2011-2016.

INTRODUCTION: A monovalent rotavirus vaccine was introduced in the Ethiopian Expanded Program on Immunization from November 2013. We compared impact of rotavirus vaccine introduction on rotavirus associated acute diarrhea hospitalizations and genotypic characteristics of rotavirus strains pre-and post-vaccine introduction. METHODS: Sentinel surveillance for diarrhea among children <5 years of age was conducted at 3 hospitals in Addis Ababa, Ethiopia from 2011 to 2017. Stool specimens were collected from enrolled children and tested using an antigen capture enzyme immunoassay. Rotavirus positive samples (156 from pre- and 141 from post-vaccination periods) were further characterized by rotavirus genotyping methods to identify the predominant G and P types circulating during the surveillance era. RESULTS: A total of 788 children were enrolled during the pre- (July 2011-June 2013) and 815 children during the post-vaccination (July 2014-June 2017) periods. The proportion of diarrhea hospitalizations due to rotavirus among children <5 years of age declined by 17% from 24% (188/788) in the pre-vaccine period and to 20% (161/185) in post-vaccine introduction era. Similarly, a reduction of 18% in proportion of diarrhea hospitalizations due to rotavirus in children <12 months of age in the post (27%) vs pre-vaccine (33%) periods was observed. Seasonal peaks of rotavirus declined following rotavirus vaccine introduction. The most prevalent circulating strains were G12P[8] in 2011 (36%) and in 2012 (27%), G2P[4] (35%) in 2013, G9P[8] (19%) in 2014, G3P[6] and G2P[4] (19% each) in 2015, and G3P[8] (29%) in 2016. DISCUSSION: Following rotavirus vaccine introduction in Ethiopia, a reduction in rotavirus associated hospitalizations was seen in all age groups with the greatest burden in children <12 months of age. A wide variety of rotavirus strains circulated in the pre- and post-vaccine introduction periods.

Sustained impact of rotavirus vaccine introduction on rotavirus gastroenteritis hospitalizations in children <5 years of age, Ghana, 2009-2016.

INTRODUCTION: Ghana introduced monovalent rotavirus vaccine in April 2012. We sought to determine the long-term impact of routine rotavirus vaccination on rotavirus gastroenteritis hospitalizations in Ghana during the first 4 years following rotavirus vaccine introduction. METHODS: Active sentinel surveillance for acute gastroenteritis hospitalizations among children <5 years of age was conducted at two sites from July 2009 through June 2016. Stool specimens were collected from enrolled children and tested by enzyme immunoassay. Changes in the proportion of all-cause gastroenteritis hospitalizations due to rotavirus pre- (July 2009-June 2012) and post-vaccine introduction (July 2012-June 2016) were compared using chi-square test. RESULTS: The proportion of acute gastroenteritis hospitalizations due to rotavirus among children <5 years of age significantly declined by 42% from a pre-vaccine median of 50% (343/684) to a post-vaccine median of 29% (118/396) (p < 0.001). The age distribution of rotavirus hospitalizations shifted toward older ages with 64% (759/1197) of rotavirus hospitalizations occurring in children <12 months of age pre-vaccine introduction to 47% (212/453) occurring in children <12 months of age post-vaccine introduction (p < 0.001). DISCUSSION: The decline in rotavirus hospitalizations following rotavirus vaccine introduction have been sustained over the first 4 years of the vaccination program in Ghana. Continued vaccination against rotavirus will ensure that this burden remains low.

Distribution of rotavirus genotypes associated with acute diarrhoea in Zimbabwean children less than five years old before and after rotavirus vaccine introduction.

BACKGROUND: Sentinel surveillance for diarrhoea is important to monitor changes in rotavirus epidemiological trends and circulating genotypes among children under 5 years before and after vaccine introduction. The Zimbabwe Ministry of Health and Child Care introduced rotavirus vaccine in national immunization program in May 2014. METHODS: Active hospital-based surveillance for diarrhoea was conducted at 3 sentinel sites from 2008 to 2016. Children aged less than 5 years, who presented with acute gastroenteritis as a primary illness and who were admitted to a hospital ward or treated at the emergency unit, were enrolled and had a stool specimen collected and tested for rotavirus by enzyme immunoassay (EIA). Genotyping of positive stools was performed using reverse-transcription polymerase chain reaction and genotyping assays. Pre-vaccine introduction, 10% of all positive stool specimens were genotyped and all adequate positive stools were genotyped post-vaccine introduction. RESULTS: During the pre-vaccine period, a total of 6491 acute gastroenteritis stools were collected, of which 3016 (46%) tested positive for rotavirus and 312 (10%) of the rotavirus positive stools were genotyped. During the post-vaccine period, a total of 3750 acute gastroenteritis stools were collected, of which 937 (25%) tested positive for rotavirus and 784 (84%) were genotyped. During the pre-vaccine introduction the most frequent genotype was G9P[8] (21%) followed by G2P[4] (12%), G1P[8] (6%), G2P[6] (5%), G12P[6] (4%), G9P[6] (3%) and G8P[4] (3%). G1P[8] (30%) was most dominant two years after vaccine introduction followed by G9P[6] (20%), G2P[4] (15%), G9P[8] (11%) and G1P[6] (4%). CONCLUSION: The decline in positivity rate is an indication of early vaccine impact. Diversity of circulating strains underscores the importance of continued monitoring and strain surveillance after vaccine introduction.

Early impact of rotavirus vaccine in under 5year old children hospitalized due to diarrhea, Swaziland.

BACKGROUND: Swaziland introduced rotavirus vaccine in the National Immunization Program, in May 2015, with the objective of reducing the burden of rotavirus diarrheal disease. We monitored the early impact of the vaccine in reducing rotavirus diarrhea. METHODS: We conducted sentinel rotavirus surveillance from January 2013 to December 2016 in children under five years of age admitted due to diarrhea attending Mbabane Government Referral Hospital in the Hhohho Region and Raleigh Fitkin Memorial Hospital in the Manzini Region. All cases had stool samples collected and tested for rotavirus antigen by enzyme immunoassay. RESULTS: Between 2013 and 2016, 596 samples were collected and tested. Rotavirus positivity reduced from average of 50.8% (172/338) (in 2013-2014 (pre vaccine period)) to 29% (24/82) in 2016, post-vaccine introduction. The median age of children with rotavirus infection increased from average of 10months in 2013-2014 to 13.7months in 2016. The peak season for all-cause diarrhea and rotavirus-specific hospitalizations among children under five years of age was June-August in all years with a blunting of the peak season in 2016. Rotavirus positivity among children 0-11months reduced from an average of 49% in 2013-2014 (116/236) to 33% (15/45) in 2016, a 33% reduction following rotavirus vaccine introduction. CONCLUSION: There has been a rapid reduction of all-cause diarrhea and rotavirus hospitalizations in Swaziland, particularly in young children and during the rotavirus season, after the introduction rotavirus vaccine. Continued surveillance is needed to monitor the long-term impact of rotavirus vaccine introduction.

Etiology of Severe Acute Watery Diarrhea in Children in the Global Rotavirus Surveillance Network Using Quantitative Polymerase Chain Reaction.

Background: The etiology of acute watery diarrhea remains poorly characterized, particularly after rotavirus vaccine introduction. Methods: We performed quantitative polymerase chain reaction for multiple enteropathogens on 878 acute watery diarrheal stools sampled from 14643 episodes captured by surveillance of children <5 years of age during 2013-2014 from 16 countries. We used previously developed models of the association between pathogen quantity and diarrhea to calculate pathogen-specific weighted attributable fractions (AFs). Results: Rotavirus remained the leading etiology (overall weighted AF, 40.3% [95% confidence interval {CI}, 37.6%-44.3%]), though the AF was substantially lower in the Americas (AF, 12.2 [95% CI, 8.9-15.6]), based on samples from a country with universal rotavirus vaccination. Norovirus GII (AF, 6.2 [95% CI, 2.8-9.2]), Cryptosporidium (AF, 5.8 [95% CI, 4.0-7.6]), Shigella (AF, 4.7 [95% CI, 2.8-6.9]), heat-stable enterotoxin-producing Escherichia coli (ST-ETEC) (AF, 4.2 [95% CI, 2.0-6.1]), and adenovirus 40/41 (AF, 4.2 [95% CI, 2.9-5.5]) were also important. In the Africa Region, the rotavirus AF declined from 54.8% (95% CI, 48.3%-61.5%) in rotavirus vaccine age-ineligible children to 20.0% (95% CI, 12.4%-30.4%) in age-eligible children. Conclusions: Rotavirus remained the leading etiology of acute watery diarrhea despite a clear impact of rotavirus vaccine introduction. Norovirus GII, Cryptosporidium, Shigella, ST-ETEC, and adenovirus 40/41 were also important. Prospective surveillance can help identify priorities for further reducing the burden of diarrhea.

c-Jun NH2-terminal kinase inhibitor bentamapimod reduces induced endometriosis in baboons: an assessor-blind placebo-controlled randomized study.

OBJECTIVE: To test the hypothesis that the c-Jun NH2-terminal kinase (JNK) inhibitor (JNKI) bentamapimod (AS602801/PGL5001) can reduce induced endometriosis in baboons. DESIGN: Prospective randomized placebo-controlled study. SETTING: Nonhuman primate research center. ANIMAL(S): Twenty baboons each underwent four laparoscopies. Initial screening laparoscopy (L1) was followed after one rest cycle by an endometriosis-induction laparoscopy (L2). Fifty days after L2, the baboons were randomized just before staging laparoscopy (L3). Treatment lasted for 60 days, followed by a post-treatment staging laparoscopy (L4). INTERVENTION(S): Randomization before a 60-day treatment in four groups: daily placebo (n = 5), daily oral administration of 20 mg/kg JNKI (n = 5), concomitant daily oral administration of 20 mg/kg JNKI and 10 mg medroxyprogesterone acetate (MPA; n = 5), or subcutaneous administration of 3 mg cetrorelix every 3 days (n = 5). MAIN OUTCOME MEASURE(S): Type, surface area and volume of endometriotic lesions, and revised American Society for Reproductive Medicine score and stage were recorded during L3 and L4. Menstrual cycle length and serum hormonal concentration were recorded before and after treatment. RESULT(S): Compared with placebo, treatment with JNKI, JNKI + PMA, or cetrorelix resulted in lower total surface area and volume of endometriotic lesions. Remodeling of red active lesions into white lesions was observed more frequently in baboons treated with JNKI + MPA than in baboons treated with JNKI only. Menstrual cycle length and serum hormonal concentration were similar between placebo and JNKI groups. CONCLUSION(S): JNKI alone was as effective as JNKI + MPA or cetrorelix in reducing induced endometriosis in baboons, but without severe side effects or effect on cycle length or serum reproductive hormones.

Intussusception incidence rates in 9 Zambian hospitals, 2007-2011: prerotavirus vaccine introduction.

BACKGROUND: Intussusception, a rare adverse event associated with rotavirus vaccines in some settings, is a common cause of intestinal obstruction in infants and toddlers globally with a peak age of 4-6 months. This age group may overlap with the extended age of administering rotavirus vaccine. METHODS: A retrospective (January 2007 to June 2009) and prospective (July 2009 to June 2012) survey was conducted in 9 Zambian hospitals. Children between 0 and 24 months who were operated on for intestinal obstruction/intussusception were identified in theatre log books. In the latter part of the survey, patients were recruited prospectively. Demographic, clinical and surgical data from hospital files were collected for each patient. RESULTS: One-hundred and five children were identified to have undergone surgery for intussusceptions. Many were boys 57.6% (57/99). Of those with complete data, intussusception was common in infants 86.9% (86/99) and many children (68.0%) were between 3 and 8 months of age with a peak age of 5-6 months. Lusaka had the highest number of children with intussusception with an estimated annual incidence rate of 12/100,000 in children <2 years of age. The overall case fatality rate was very high 33.7% (31/92). CONCLUSION: Intussusception was common in infants with a peak age of 5-6 months, and of particular concern is the group of 2-4 months the age of rotavirus vaccination. The estimated incidence rate of 12/100,000 is an underestimate as many cases may not present for care. The high case fatality rate of 33.7% is due to both delayed presentation and diagnosis in hospital.

Preparing for safety monitoring after rotavirus vaccine implementation: a retrospective review of intussusception cases among children at a large teaching hospital in Rwanda, 2009-2012.

BACKGROUND: In some settings, rotavirus vaccines have been associated with a small risk of intussusception. This study describes the demographics, clinical characteristics and outcomes of children with intussusception in Rwanda before vaccine introduction in May 2012. METHODS: We retrospectively reviewed data on pediatric patients treated for intussusception at University Teaching Hospital of Kigali from January 2009 to June 2012. Hospital registries were reviewed to identify intussusception cases. Archived patient files were abstracted to collect data on demographics, clinical presentation, surgery and outcome. RESULTS: During the study period, 70 children ≤19 years of age were treated for intussusception and patient files were retrieved for 60 (86%) cases. Over half of patients (58%) were <1 year of age and 90% were transferred from a district hospital. Only 30% of patients presented within 3 days of symptom onset and 35% experienced a delay of ≥6 hours between surgical review and surgery. Surgical complications were experienced by 35% of children. Over 1 quarter (28%) of children died. Compared with children who survived, children who died were significantly more likely to have experienced complications (21% vs. 71%; P < 0.001) and to be female (28% vs. 65%; P = 0.009). DISCUSSION: Mortality due to intussusception was high among Rwanda children. Delays in presentation and treatment were common. Assessing trends in the number of cases to monitor for vaccine-associated intussusception will be difficult. Additional work is needed to further understand risk factors for mortality, to calculate incidence rates and to monitor the safety of the rotavirus vaccination program.

Baboon spermatology: basic assessment and reproducibility in olive baboons (Papio anubis).

BACKGROUND: Development of a reproducible baboon in vitro fertilization (IVF) system require optimized and reproducible sperm parameters. The objective of this study was to document basic spermatology values and investigate the reproducibility of these variables in the same baboons 1 or 3 months later in a larger number of baboons. METHODS: In this prospective study, sperm quality (semen volume, pH, concentration, motility, morphology and size) was evaluated in 27 sperm samples obtained from 9 baboons electroejaculated three times with a time interval of 1 month (between first and second sample collection) and 3 months (between second and third round sample collection). RESULTS: Baseline sperm values for semen volume (0.5 ± 0.3 ml), pH (7.5 ± 0.3), concentration (54.2 ± 19.3 million/ml), motility (67.3 ± 18.5%) and morphology (89.2 ± 4.8%) were similar to sperm samples obtained after 1 or 3 months (P > 0.05). Head, midpiece and tail abnormalities were rarely observed (0-9%). Sperm dimensions were characterized by a tail length of 69.6 ± 13.9 µm, a head width of 2.41 ± 0.43 µm and a head length of 3.49 ± 0.6 µm. CONCLUSION: Sperm quality was not affected by repeated electroejaculation with time intervals of 1 or 3 months, suggesting that the same baboon can participate multiple times in reproductive research.

Randomized comparison of different ovarian stimulation regimens for assisted reproductive technology in baboons (Papio anubis).

OBJECTIVE: To compare different methods of ovarian stimulation (OS) for assisted reproductive technology in baboons. DESIGN: Prospective randomized study. SETTING: Institute of primate research. ANIMAL(S): Baboons (n = 10) were randomized into two groups (of five animals each) during three different cycles to compare six protocols of OS. INTERVENTION(S): Cycle 1: clomiphene citrate (CC) alone (group CC) versus CC and GnRH agonist (group CC-Ag); cycle 2: recombinant gonadotropins (GON) without GnRH agonist (group GON) versus GON and depot GnRH agonist (group GON-AgDepo-1); cycle 3: GON and depot GnRH agonist (group GON-AgDepo-2) versus GON and daily GnRH agonist in a classic long protocol (group GON-Ag). Oocyte aspiration was performed 34-36 hours after injecting 5,000 IU rhCG, followed by fertilization via intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Number and quality of oocytes retrieved and their fertilization rate. RESULT(S): More metaphase II (MII) oocytes were retrieved using the GON-AgDepo-1 (n = 12; 64% MII), GON-AgDepo-2 (n = 9; 79% MII), GON-Ag (n = 16; 88% MII), and GON (n = 6; 59% MII) protocols compared with the CC (n = 9; 15% MII) and CC-Ag (n = 14; 20% MII) protocols. Fertilization by ICSI varied between 43% and 71%. CONCLUSION(S): In baboons, long and depot protocols yield similar numbers of MII oocytes; however, depot protocol may be preferable because only one injection of GnRH agonist is needed.

Peroxisome proliferator-activated receptor-(gamma) receptor ligand partially prevents the development of endometrial explants in baboons: a prospective, randomized, placebo-controlled study.

A prospective, randomized, placebo-controlled study was conducted in a baboon model to determine if a thiazolidinedione agonist of peroxisome proliferator-activated receptor-gamma, pioglitazone, can impede the development of endometriosis. Endometriosis was induced using laparoscopic, intrapelvic injection of eutopic menstrual endometrium, previously incubated with placebo or pioglitazone for 30 min, in 12 female baboons with a normal pelvis that had undergone at least one menstrual cycle since the time of captivity. At this point, the 12 baboons were randomized into two groups and treated from the day of induction. They received either PBS tablets (n = 6, placebo control, placebo tablets once a day by mouth) or pioglitazone (n = 6, test drug, 7.5 mg by mouth each day). A second and final laparoscopy was performed in the baboons to record the extent of endometriotic lesions between 24 and 42 d after induction (no difference in length of treatment between the two groups, P = 0.38). A videolaparoscopy was performed to document the number and surface area of endometriotic lesions. The surface area and volume of endometriotic lesions were significantly lower in pioglitazone treated baboons than the placebo group (surface area, 48.6 vs. 159.0 mm(2), respectively, P = 0.049; vol, 23.7 vs. 131.8 mm(3), respectively, P = 0.041). The surface area (3.5 vs. 17.8 mm(2), P = 0.017, pioglizatone vs. placebo) and overall number (1.5 vs. 9.5, P = 0.007, pioglizatone vs. placebo) of red lesions were lower in the pioglitazone group. A peroxisome proliferator-activated receptor-gamma ligand, pioglitazone, effectively reduced the initiation of endometriotic disease in the baboon endometriosis model. Using this animal model, we have shown that thiazolidinedione is a promising drug for preventive treatment of endometriosis.

Separate and combined effects of caffeine and dbcAMP on olive baboon (Papio anubis) sperm.

BACKGROUND: Improvement of baboon sperm capacitation is necessary for achieving high in vitro fertilization (IVF) rates in baboons. In this study, we evaluated separate and combined effects of caffeine and dbcAMP on baboon sperm capacitation. METHODS: Sixteen male baboons (n = 16) were electroejaculated. Each sperm sample was divided into two aliquots: one for chemical activation and the other untreated control. Group 1: dbcAMP (n = 6); Group 2: caffeine (n = 6) and Group 3: combination of caffeine and dbcAMP (n = 4). In each aliquot, sperm motility after 30 minutes of incubation was evaluated as well as zona pellucida (ZP) binding ability after overnight incubation with 4-5 ZP from unfertilized human oocytes. RESULTS: Sperm motility and ZP binding ability in all chemically activated groups increased significantly as compared to their respective controls (P < 0.05). CONCLUSION: Combined and separate effects of caffeine and dbcAMP increases baboon sperm motility and ZP binding ability and may improve baboon IVF.

High prevalence of species D human adenoviruses in fecal specimens from Urban Kenyan children with diarrhea.

Human adenoviruses (HAdVs) cause a wide range of clinical syndromes and are classified in seven species, A-G, comprising 52 serotypes. HAdV-A31, -F40, and -F41 have been associated with diarrhea in infants and young children. In developing countries gastroenteritis is a major cause of morbidity and mortality in children and, in comparison to rotaviruses, there are no data on the HAdVs associated with diarrhea in pediatric patients in Kenya. This study investigates the prevalence and genotypes of HAdVs in 278 stool specimens (211 diarrheal; 67 non-diarrheal) from children < or =14 years of age in urban and rural areas in Kenya. Stool specimens were screened for HAdVs using a nested polymerase chain reaction and the HAdVs genotyped by sequence analysis of a conserved hexon gene fragment. HAdVs were detected in 104/278 (37.4%) of the stool specimens: 35/43 (81.4%) of diarrheal and 10/61 (16.4%) of non-diarrheal stool specimens from children in an urban hospice; 25/94 (26.6%) of diarrheal specimens from urban children and 34/80 (42.5%) of diarrheal specimens from children in a rural area. Species D HAdVs were identified as the most prevalent HAdV species in diarrheal stool specimens from urban children comprising 18/37 (48.6%) of the strains identified. In contrast HAdV species F predominated in pediatric diarrheal specimens from the rural area, being identified in 7/16 (43.8%) of the characterized strains. This study provides valuable new data on the prevalence and distribution of HAdV genotypes in diarrheal stool specimens in Kenya and Africa, and highlights the necessity for further investigations.

Role of cytokines in the endometrial-peritoneal cross-talk and development of endometriosis.

A clear picture of the dynamic relationship between the endometrium and peritoneum is emerging as both tissues may participate in the spontaneous development of endometriosis. Various adhesion molecules, pro-inflammatory cytokines and chemoattractants cytokines have emerged as central coordinators of endometrial-peritoneal interactions. The peritoneal microenvironment which consists of the peritoneal fluid, normal peritoneum and peritoneal endometriotic lesions may play an active role in the pathogenesis of endometriosis, by harbouring most inflammatory responses that are triggered by the presence of endometrial cells, leading to recruitment of activated macrophages and leukocytes locally. Menstrual endometrium has the ability to bond and invade the peritoneal tissue. In baboons intrapelvic injection of menstrual endometrium permits the study of early endometrial-peritoneal interaction in an in vivo culture microenvironment and can lead to important insight in the early development of endometriotic lesions. In this review, we discuss the roles of the endometrial-peritoneal interactions, not only in disease development but also in the broader process of aetiopathogenesis.

Menstrual cycle synchronization, ovarian stimulation, and in vitro fertilization in olive baboons (Papio anubis): a prospective randomized study.

OBJECTIVE: To synchronize the baboon menstrual cycle and to compare different methods of ovarian stimulation for IVF in baboons. DESIGN: Prospective randomized study. SETTING: Institute of Primate Research, Nairobi, Kenya. ANIMAL(S): Ten female baboons were treated with an oral contraceptive (33 +/- 8 days) and randomized for ovarian stimulation in two cycles. INTERVENTION(S): In cycle 1 (C1), baboons were stimulated as follows: clomiphene citrate (CC) for 5 days followed by antagonist (group CC-1, n = 3); recombinant gonadotropins (rGn: rFSH and rLH) with antagonist (group antagon-1, n = 3); and long GnRH agonist protocol (group LP-1, n = 4). After 1- month rest, in cycle 2 (C2), the baboons were stimulated as follows: CC for 8 days without antagonist (group CC-2, n = 2); short GnRH agonist protocol (group SP-2, n = 4); long GnRH agonist protocol (group LP-2, n = 4). Oocyte aspiration was performed 34-36 hours after injecting 5000 IU recombinant hCG; the oocytes were then fertilized. MAIN OUTCOME MEASURE(S): Oocytes retrieved and fertilization rate. RESULT(S): Withdrawal bleeding occurred 4 +/- 1 days after the cessation of the contraceptive. Ovarian stimulation using the different protocols resulted in the following mean numbers of retrieved oocytes: LP-1, n = 19; LP-2, n = 19; CC-1, n = 4; CC-2, n = 4; antagon-1, n = 9; and SP-2, n = 14. Fertilization by intracytoplasmic sperm injection varied (23%-54%). CONCLUSION(S): The baboon menstrual cycle can be synchronized using an oral contraceptive. A long GnRH agonist protocol for ovarian stimulation may be suitable for ovarian stimulation in baboons.

Feasibility of ultrasound-guided percutaneous samplings in the pregnant baboon: a model for studies on transplacental transport.

OBJECTIVE: A study was conducted to test the feasibility of cordocenteses and amniocenteses at different gestational ages in pregnant baboons. STUDY DESIGN: Experiments were performed in 10 pregnant baboons at a median gestational age of 131 (range 92-169) days. At different time intervals, percutaneous samplings of amniotic fluid and fetal blood were performed under ultrasound guidance. Simultaneously, maternal blood samples were drawn. RESULTS: With a median fetal weight of 431 g (range 111-690 g), 29 of 30 cordocenteses (96.6%) and all 30 amniocenteses and maternal samplings (100%) were successful in obtaining the required quantities for analysis. One cordocentesis was abandoned because of insufficient visualization of the umbilical cord due to a placental haemorrhage. CONCLUSION: Percutaneous amniocentesis and cordocentesis can be performed with a high success rate in the pregnant baboon model. In combination with a 100% success rate in obtaining simultaneous maternal blood samples, this method is able to provide data on transplacental transport.

Endometrial and peritoneal expression of aromatase, cytokines, and adhesion factors in women with endometriosis.

OBJECTIVE: To examine messenger (m) RNA expression of aromatase, cytokines, and adhesion factors in women with and without endometriosis. DESIGN: Patients with endometriosis were compared with control patients. SETTING: University Hospital Gasthuisberg, Leuven, Belgium. PATIENT(S): A total of 35 patients who had laparoscopic surgery during the luteal phase (n = 20) or the menstrual phase (n = 15) were selected for this study based on cycle phase and presence/absence of endometriosis. INTERVENTION(S): Tissues of endometrium and macroscopically normal peritoneum were collected during hysteroscopy and laparoscopic surgery, respectively, from 24 women with revised American Society for Reproductive Medicine stage (rASRM) stages I-II (n = 12) and III-IV (n = 12) endometriosis and 11 control patients with normal pelvic. Tissue samples were selected from a tissue bank, based on the phase of the cycle (menstrual or luteal) and the presence/absence of endometriosis. MAIN OUTCOME MEASURE(S): The mRNA levels of aromatase, vimentin, vascular cell adhesion molecule 1 (VCAM-1), alpha(V) and beta(3) integrins, interleukin (IL)-1 beta, regulated on activation normal T-cell expressed and secreted (RANTES), and monocyte chemotactic protein 1 (MCP-1) were evaluated using real-time reverse transcriptase polymerase chain reaction. RESULT(S): During menstrual phase, increased endometrial mRNA levels of alpha(V) integrin, combined alpha(V)beta(3) integrins, and increased peritoneal IL-1 beta mRNA levels--but decreased peritoneal MCP-1 mRNA levels--were observed in women with endometriosis compared with control subjects. During luteal phase, endometrial mRNA levels of IL-1 beta and RANTES were increased in women with endometriosis compared with control subjects. Endometrial aromatase mRNA expression was higher in women with endometriosis than in control subjects in combined phases. Women with endometriosis had increased peritoneal mRNA expression of RANTES and VCAM-1 during menstrual compared with luteal phase. CONCLUSION(S): Aberrant mRNA expression of aromatase, cytokines, and adhesion factors in endometrium and peritoneum suggests that both tissues are involved in the pathogenesis of endometriosis.