Immune Recognition versus Immune Evasion Systems in Zika Virus Infection.

The reemergence of the Zika virus (ZIKV) infection in recent years has posed a serious threat to global health. Despite being asymptomatic or mildly symptomatic in a majority of infected individuals, ZIKV infection can result in severe manifestations including neurological complications in adults and congenital abnormalities in newborns. In a human host, ZIKV is primarily recognized by RIG-like receptors and Toll-like receptors that elicit anti-viral immunity through the secretion of type I interferon (IFN) to limit viral survival, replication, and pathogenesis. Intriguingly, ZIKV evades its host immune system through various immune evasion strategies, including suppressing the innate immune receptors and signaling pathways, mutation of viral structural and non-structural proteins, RNA modulation, or alteration of cellular pathways. Here, we present an overview of ZIKV recognition by the host immune system and the evasion strategies employed by ZIKV. Characterization of the host-viral interaction and viral disease mechanism provide a platform for the rational design of novel prophylactic and therapeutic strategies against ZIKV infection.

Zika Virus Vaccine: The Current State of Affairs and Challenges Posed by Antibody-Dependent Enhancement Reaction.

Infection caused by the Zika virus (ZIKV) can lead to serious neurological complications such as microcephaly in neonates. At present, no approved ZIKV vaccine is available, but few vaccine candidates are undergoing clinical trial. One major challenge faced is antibody-dependent enhancement (ADE) reaction that may provoke severe outcome in subsequent infection by ZIKV or other flaviviruses. Thus, more efforts should be dedicated to understanding ADE in designing a safe and effective vaccine to minimize the consequence of the potentially fatal infection's complications and to tackle potential ZIKV reemergence. This review discusses different types of ZIKV vaccine candidates that are currently underway in various stages of preclinical and clinical evaluations.

The prevalence of menstrual disorders and premenstrual syndrome among adolescent girls living in North Borneo, Malaysia: a questionnaire-based study.

BACKGROUND: This study aimed to determine menstrual characteristics and related morbidities among adolescent girls living in Sabah, North Borneo, a less-developed state in Malaysia. METHODS: Data were obtained from a quantitative survey conducted in three government high schools located in Ranau, Sabah. The participants were adolescent girls who had attained menarche between the ages of 14 and 19. RESULTS: Based on the analysis of questionnaires completed by 757 adolescent girls, the mean age at the time of the survey was 17 ± 1.4 years, and the mean menarche age was 12.2 ± 1.1 years. Our data demonstrated that 85.7% of the participants experienced dysmenorrhoea, of which at least 42.1% (mean pain score ± SD: 4.81 ± 0.76, 95% confidence interval (CI) 4.72, 4.90) experienced moderate dysmenorrhoea, and 11.2% (mean pain score ± SD: 7.86 ± 0.94, 95% CI 7.64, 8.08) experienced severe dysmenorrhoea. Over 70% of these girls complained of tiredness, headache, and appetite changes during menses. CONCLUSIONS: The prevalence of menstrual disorders and related morbidities was high among the girls residing in Sabah. Reproductive health issues in rural and socioeconomically deprived areas remains poorly addressed. The main consequence of neglecting menstrual disorders and their related morbidities is impaired future sexual reproductive health in adults. Thus, addressing adolescent reproductive health issues is crucial, especially for girls living in areas where access to healthcare is difficult. The information gathered from this study can be used to strategize effective interventions to improve adolescents' reproductive health status in rural areas.

Review of recent evidence on the management of heartburn in pregnant and breastfeeding women.

Gastroesophageal reflux disease (GERD) is one the most common medical complaints in pregnant women. Some women continue to experience GERD symptoms after delivery. Effective management of GERD symptoms is important to improve productivity and quality of life. Management of heartburn in pregnant and breastfeeding women involves lifestyle modifications, dietary modifications, non-pharmaceutical remedies and pharmaceutical drugs. For most patients, lifestyle/dietary modifications are helpful in reducing GERD symptoms. For patients who require a more intense intervention, various types of pharmaceutical drugs are available. However, the suitability of each treatment for use during pregnancy and lactation must be taken into consideration. This article explores the reported efficacy and safety of these treatment options in pregnant and breastfeeding women. Recommended treatment algorithm in pregnant and breastfeeding women have been developed.

The Factors Associated with Prevention and Control Practices against Zika Virus Infection among Pregnant Women in Malaysia, a Dengue-Endemic Country.

The aim of this study was to analyze the prevention and control practices against Zika virus (ZIKV) infection among pregnant women in Malaysia. A cross-sectional study was conducted among pregnant women who received antenatal care. Only 7.8% reported that they abstained from sex or used barrier methods during sexual intercourse to prevent ZIKV transmission. The odds of abstaining from sex or using barrier methods were significantly higher among the Chinese ethnic group than the Malay ethnic group (odds ratio [OR] = 4.569; 95% confidence interval [CI]: 2.696-7.743). A total ZIKV knowledge score of 12-24 was also significantly associated with higher odds of abstaining from sex or using barrier methods than a score of 0-11 (OR = 2.819; 95% CI: 1.682-4.725). In total, 38.6% of women had a higher mean total score for all the current mosquito control practices than they did before hearing of ZIKV. Participants living in bungalows or village houses (OR = 2.006; 95% CI: 1.023-3.936) and low-rise houses (OR = 1.566; 95% CI: 1.109-2.212) were more likely to have a higher mean total score of current mosquito control practices than the practices before hearing of ZIKV compared to those in high-rise houses. The lack of ZIKV knowledge and control practices provides insight for the pre-emptive and prompt development of health education systems for pregnant women during antenatal care visits.

Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Quadrivalent Human Papillomavirus Vaccine in Boys and Girls 9-13 Years of Age in Malaysia: A Phase IIIb, Randomized, Open-label Study.

BACKGROUND: Incorporating dengue vaccination within existing vaccination programs could help improve dengue vaccine coverage. We assessed the immunogenicity and safety of a quadrivalent human papillomavirus (HPV) vaccine administered concomitantly or sequentially with a tetravalent dengue vaccine (CYD-TDV) in healthy children 9-13 years of age in Malaysia. METHODS: In this phase IIIb, open-label, multicenter study (NCT02993757), participants were randomized 1:1 to receive 3 CYD-TDV doses 6 months apart and 2 doses of quadrivalent HPV vaccine concomitantly with, or 1 month before (sequentially), the first 2 CYD-TDV doses. Only baseline dengue-seropositive participants received the 3 doses. Antibody levels were measured at baseline and 28 days after each injection using an enzyme-linked immunosorbent assay for HPV-6, -9, -16 and -18, and the 50% plaque reduction neutralization test for the 4 dengue serotypes; immunogenicity results are presented for baseline dengue-seropositive participants. Safety was assessed throughout the study for all participants. RESULTS: At baseline, 197 of 528 (37.3%) randomized participants were dengue-seropositive [n = 109 (concomitant group) and n = 88 (sequential group)]. After the last HPV vaccine dose, antibody titers for HPV among baseline dengue-seropositive participants were similar between treatment groups, with between-group titer ratios close to 1 for HPV-6 and 0.8 for HPV-11, -16, and -18. After CYD-TDV dose 3, dengue antibody titers were similar between treatment groups for all serotypes [between-group ratios ranged from 0.783 (serotype 2) to 1.07 (serotype 4)]. No safety concerns were identified. CONCLUSIONS: The immunogenicity and safety profiles of CYD-TDV and quadrivalent HPV vaccines were unaffected when administered concomitantly or sequentially in dengue-seropositive children.

New modified undermined suture technique for rectus muscle re-approximation at cesarean delivery-Case report.

INTRODUCTION: Diastasis recti abdominis (DRA) is characterized by the separation of the two rectus abdominis muscle along the linea alba. A newly modified undermined suture rectus muscle technique at cesarean delivery is created with improved post-operative outcome. PRESENTATION OF CASE: A 30-year-old woman, who had a previous cesarean delivery, opted for another cesarean section (CS) during this pregnancy. She claimed that her tummy was lax after her first experience of CS even with regular exercise. A standard CS procedure was carried out along with the new modified undermined suture technique for rectus muscle re-approximation. Post-operatively, the pain score was 2/10 without any evidence of hematoma, seromas or infection and the patient ambulates well. The patient did not complain of any pain or complications upon follow up after 2 weeks and 2 months post-operation. She claims that her abdomen is firmer, flatter and more stable compared to her previous operation experience. DISCUSSION: This newly modified method prevents any defect or weakness on the anterior abdominal wall even if the rectus muscles fail to oppose itself during the healing process. It also mimics the function of the linea alba and avoid interrupting the contraction or injuring the muscle in order to avoid pain. Adhesion of the anterior uterine wall and the rectus sheath can be prevented by closure of the rectus muscle and burying the suture material within the muscle. CONCLUSION: The newly modified undermined suture rectus muscle technique at cesarean delivery has the potential to improved patient's post-operative satisfaction.

Diversity of endocervical microbiota associated with genital Chlamydia trachomatis infection and infertility among women visiting obstetrics and gynecology clinics in Malaysia.

The cervical microbiota constitutes an important protective barrier against the invasion of pathogenic microorganisms. A disruption of microbiota within the cervical milieu has been suggested to be a driving factor of sexually transmitted infections. These include Chlamydia trachomatis which frequently causes serious reproductive sequelae such as infertility in women. In this study, we profiled the cervical microbial composition of a population of 70 reproductive-age Malaysian women; among which 40 (57.1%) were diagnosed with genital C. trachomatis infection, and 30 (42.8%) without C. trachomatis infection. Our findings showed a distinct compositional difference between the cervical microbiota of C. trachomatis-infected subjects and subjects without C. trachomatis infection. Specifically, significant elevations of mostly strict and facultative anaerobes such as Streptococcus, Megasphaera, Prevotella, and Veillonella in the cervical microbiota of C. trachomatis-positive women were detected. The results from the current study highlights an interaction of C. trachomatis with the environmental microbiome in the endocervical region.

The Effectiveness of Hypnosis Intervention in Alleviating Postpartum Psychological Symptoms.

Psychological symptoms, particularly postpartum depression, may impair women's well-being after childbirth. Mind-body treatments such as hypnosis are available to help prepare women to maintain or improve their well-being postpartum. The aims of the present study are to determine the effectiveness of a hypnosis intervention in alleviating psychological symptoms (stress, anxiety, and depression) and the symptoms of postpartum depression. A quasi-experimental design was utilized in this study. The experimental group participants (n = 28) received a hypnosis intervention at weeks 16, 20, 28, and 36 of their pregnancies. Participants in the control group (n = 28) received routine prenatal care. The final data collection, occurring at two months postpartum, included 16 women from the experimental group and 11 women from the control group. The Depression Anxiety Stress Scale-21 (DASS-21) was used to measure psychological symptoms, and postpartum depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS). The results at two months postpartum showed that the experimental group had significantly lower postpartum anxiety than the control group (M = 2.88 versus M = 38.36, p = .023). Similarly, the experimental group had significantly lower postpartum depressive symptoms than the control group (M = 1.25 versus M = 6.73, p < .002). Group differences in postpartum stress symptoms were not significant (p = .363). Finally, the results indicated that the experimental group experienced reduced postpartum depression when compared to the control group (M = 5.69 versus M = 10.64, p < .001). Thus, hypnosis conducted during pregnancy may promote improvements in psychological well-being postpartum.

CPAF, HSP60 and MOMP antigens elicit pro-inflammatory cytokines production in the peripheral blood mononuclear cells from genital Chlamydia trachomatis-infected patients.

BACKGROUND: Persistent inflammation caused by Chlamydia trachomatis in the female genital compartment represents one of the major causes of pelvic inflammatory disease (PID), ectopic pregnancy and infertility in females. Here, we examined the pro-inflammatory cytokine response following stimulation with three different types of C. trachomatis antigens, viz. chlamydial protease-like factor (CPAF), heat shock protein 60 (HSP60) and major outer membrane protein (MOMP). METHODS: A total of 19 patients with genital C. trachomatis infection and 10 age-matched healthy controls were recruited for the study. Peripheral blood mononuclear cells (PBMCs) isolated from genital C. trachomatis-infected females were cultured in the presence of CPAF, HSP60 and MOMP antigens, and cytokines were measured by ELISA assay. RESULTS: We reported that pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) were robustly secreted following antigenic exposure. Notably, CPAP and MOMP were more potent in triggering IL-1ß, as compared to HSP60. Elevated levels of the proinflammatory cytokines were also noted in the samples infected with plasmid-bearing C. trachomatis as compared to those infected with plasmid-free strains. CONCLUSIONS: Our study highlights distinct ability of chlamydial antigens in triggering pro-inflammatory response in the host immune cells.

Sera of patients with systemic lupus erythematosus cross-neutralizes dengue viruses.

Dengue is the most prevalent mosquito-borne disease in Southeast Asia, where the incidence of systemic lupus erythematosus (SLE) is approximately 30 to 53 per 100,000. Severe dengue, however, is rarely reported among individuals with SLE. Here, whether sera of patients with SLE cross-neutralize dengue virus (DENV) was investigated. Serum samples were obtained from individuals with SLE who were dengue IgG and IgM serology negative. Neutralization assays were performed against the three major DENV serotypes. Of the dengue serology negative sera of individuals with SLE, 60%, 61% and 52% of the sera at 1/320 dilution showed more than 50% inhibition against dengue type-1 virus (DENV-1), DENV-2 and DENV-3, respectively. The neutralizing capacity of the sera was significantly greater against DENV-1 (P < 0.001) and DENV-3 (P < 0.01) than against DENV-2 (P < 0.05). Neutralization against the DENV correlated with dengue-specific IgG serum titers below the cut-off point for dengue positivity. Depletion of total IgG from the sera of patients with SLE resulted in significant decreases of up to 80% in DENV inhibition, suggesting that IgG plays an important role. However, some of the SLE sera was still able to neutralize DENV, even with IgG titers <0.1 OD absorbance. Our findings suggest that sera of patients with SLE contain IgG, and possibly other type of antibodies, that can cross-neutralize DENV, which may explain the rarity of severe dengue in individuals with SLE. Further studies, are needed to further substantiate this finding and to elucidate the specific neutralizing epitopes recognized by the sera of individuals with SLE.

Medical genetics in developing countries in the Asia-Pacific region: challenges and opportunities.

Advances in genetic and genomic technology changed health-care services rapidly in low and middle income countries (LMICs) in the Asia-Pacific region. While genetic services were initially focused on population-based disease prevention strategies, they have evolved into clinic-based and therapeutics-oriented service. Many LMICs struggled with these noncommunicable diseases and were unprepared for the needs of a clinical genetic service. The emergence of a middle class population, the lack of regulatory oversight, and weak capacity-building in medical genetics expertise and genetic counseling services led to a range of genetic services of variable quality with minimal ethical oversight. Some of the current shortcomings faced include the lack of awareness of cultural values in genetic health care, the variable stages of socioeconomic development and educational background that led to increased demand and abuse of genetics, the role of women in society and the crisis of gender selection, the lack of preventive and care services for genetic and birth defects, the issues of gene ethics in medicine, and the lack of understanding of some religious controversies. These challenges provide opportunities for both developing and developed nations to work together to reduce the inequalities and to ensure a caring, inclusive, ethical, and cost-effective genetic service in the region.

The Effectiveness of Hypnosis Intervention for Labor: An Experimental Study.

Hypnosis has been shown to help pregnant women experience improved labor and postpartum periods. The present study compares the differences between experimental (n = 23) and control groups (n = 22) on specific variables measured both during labor and 24 hr postpartum. The participants in the experimental group received the hypnosis intervention at weeks 16, 20, 28, and 36 of pregnancy, while those in the control group received only routine antenatal care. The data collected at the labor stage describe the length of the labor stage, pain relief used during labor, the method of delivery, and the type of assisted vaginal delivery. Within 24 hr of delivery, data on neonatal birth weight, neonatal Apgar scores, and self-reported pain were obtained. The labor stage results showed no significant differences in the length of the second and third stages of labor. Although the participants in the experimental group reported higher pain levels immediately prior to, during, and immediately after delivery, their use of pethidine during labor was significantly lower than the control group participants. None of the experimental group participants opted for an epidural, and they had a greater number of assisted vaginal deliveries than the control group participants. The 24 hr postpartum results showed that the neonates of the experimental group participants had nonsignificantly higher Apgar scores than those of the women in the control group. Group differences in neonatal weight were not significant. The results of the present study indicate that hypnosis is useful for assisting pregnant women during labor and the postpartum period.

Attitudes towards Zika screening and vaccination acceptability among pregnant women in Malaysia.

The aim of this study was to examine the willingness of pregnant women to have prenatal screening for the Zika virus (ZIKV). Secondly, the study also assessed the acceptability of a hypothetical Zika vaccination and its association with the health belief model (HBM) constructs. A cross-sectional study was conducted from 4th October to 11th November 2016, among pregnant women who attended antenatal care at the University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia. The majority (81.8%) was willing to be tested for ZIKV and 78% felt that their spouse would be willing to be tested for ZIKV. A total of 94% expressed a willingness to receive a Zika vaccination if available. The participants expressed high perceived benefits of a ZIKV vaccination. Although many have a high perception of the severity of ZIKV, the proportion with a strong perception of their susceptibility to ZIKV was low. In the multivariate analysis of all the HBM constructs, cue-to-action, namely physician recommendation (odds ratio [OR]=2.288; 95% confidence interval [CI] 1.093-4.793) and recommendation from friends or relatives (OR=4.030; 95% CI 1.694-9.587), were significantly associated with a willingness to be vaccinated against ZIKV. The favourable response to a Zika vaccination implies that more research attention has to be given to develop a vaccine against ZIKV. Should the vaccine be available in the future, publicity and healthcare providers would play a vital role in ensuring vaccine uptake among pregnant women.

Date fruit consumption at term: Effect on length of gestation, labour and delivery.

Labour induction and augmentation with Prostaglandin and Oxytocin are well established as standard practice worldwide. They are safe when used judiciously, but may be associated with maternal and neonatal morbidities. Other safer alternatives have been studied including dates consumption during late pregnancy with various outcomes. The aim of this randomised controlled trial was to investigate the effect of date fruit consumption during late pregnancy on the onset of labour and need for induction or augmentation of labour. A total of 154 nulliparous women with an uncomplicated singleton pregnancy were randomly allocated to either dates-consumer (77) or control group (77). The women in the dates-consumer group had significantly less need for augmentation of labour and longer intervention to delivery interval. There was no significant difference in the onset of spontaneous labour. Dates consumption reduces the need for labour augmentation but does not expedite the onset of labour. Impact statement • Dates fruit consumption during late pregnancy has been shown to positively affect the outcome of labour and delivery. In this study, date consumption reduced the need for labour augmentation with oxytocin but did not expedite the onset of labour. Therefore, dates consumption in late pregnancy is a safe supplement to be considered as it reduced the need for labour intervention without any adverse effect on the mother and child. This further supports the finding of earlier studies.

Impact of Hypnosis Intervention in Alleviating Psychological and Physical Symptoms During Pregnancy.

Physical symptoms (e.g., vomiting) and psychological symptoms (stress, anxiety, and depression) during pregnancy are common. Various strategies such as hypnosis are available to reduce these symptoms. The objective of the authors in this study is to investigate the impact of a hypnosis intervention in reducing physical and psychological symptoms during pregnancy. A pre-test/post-test quasi-experimental design was employed in this study. The hypnosis intervention was given to the experimental group participants at weeks 16 (baseline), 20 (time point 1), 28 (time point 2), and 36 (time point 3) of their pregnancy. Participants in the control group received only the traditional antenatal care. Participants from both groups completed the Depression Anxiety Stress Scale-21 (DASS-21) and a Pregnancy Symptoms Checklist at weeks 16, 20, 28 and 36 of pregnancy. Results indicated that stress and anxiety symptoms were significantly reduced for the experimental group, but not for the control group. Although mean differences for the depressive symptoms were not significant, the experimental group had lower symptoms at time point 3. The physical symptoms' results showed significant group differences at time point 3, indicating a reduction in the experience of physical symptoms for the experimental group participants. Our study showed that hypnosis intervention during pregnancy aided in reducing physical and psychological symptoms during pregnancy.

Prevalence of plasmid-bearing and plasmid-free Chlamydia trachomatis infection among women who visited obstetrics and gynecology clinics in Malaysia.

BACKGROUND: The 7.5 kb cryptic plasmid of Chlamydia trachomatis has been shown to be a virulence factor in animal models, but its significance in humans still remains unknown. The aim of this study was to investigate the prevalence and potential involvement of the C. trachomatis cryptic plasmid in causing various clinical manifestations; including infertility, reproductive tract disintegrity, menstrual disorder, and polycystic ovarian syndrome (PCOS) among genital C. trachomatis-infected patients. RESULTS: A total of 180 female patients of child bearing age (mean 30.9 years old, IQR:27-35) with gynecological complications and subfertility issues, who visited Obstetrics and Gynecology clinics in Kuala Lumpur, Malaysia were recruited for the study. Prevalence of genital chlamydial infection among these patients was alarmingly high at 51.1% (92/180). Of the 92 chlamydia-infected patients, 93.5% (86/92) were infected with plasmid-bearing (+) C. trachomatis while the remaining 6.5% (6/92) were caused by the plasmid-free (-) variant. Our data showed that genital C. trachomatis infection was associated with infertility issues, inflammation in the reproductive tract (mucopurulent cervicitis or endometriosis), irregular menstrual cycles and polycystic ovarian syndrome (PCOS). However, no statistical significance was detected among patients with plasmid (+) versus plasmid (-) C. trachomatis infection. Interestingly, plasmid (+) C. trachomatis was detected in all patients with PCOS, and the plasmid copy numbers were significantly higher among PCOS patients, relative to non-PCOS patients. CONCLUSION: Our findings show a high incidence of C. trachomatis infection among women with infertility or gynecological problems in Malaysia. However, due to the low number of plasmid (-) C. trachomatis cases, a significant role of the plasmid in causing virulence in human requires further investigation of a larger cohort.