A randomized trial of endometrial scratching in women with PCOS undergoing ovulation induction cycles.

RESEARCH QUESTION: Does endometrial scratching improve the chance of a live birth in women with polycystic ovary syndrome (PCOS) undergoing ovulation induction and trying to conceive? DESIGN: An international, multicentre, randomized, sham-controlled trial across six fertility clinics in three countries (New Zealand, UK and Brazil). Women with a diagnosis of PCOS who were planning to commence ovulation induction cycles (at least three cycles) in order to conceive were randomly assigned to receive the pipelle (scratch) procedure or a sham (placebo) procedure in the first cycle of ovulation induction. Women kept a diary of ovulation induction and sexual intercourse timing over three consecutive cycles and pregnancies were followed up to live birth. Primary outcome was live birth and secondary outcomes were clinical pregnancy, ongoing pregnancy, multiple pregnancy, adverse pregnancy outcomes, neonatal outcomes, bleeding following procedure and pain score following procedure. RESULTS: A total of 117 women were randomized; 58 to the scratch group and 59 to the sham group. Live birth occurred in 11 (19%) women in the scratch group and 14 (24%) in the sham group (odds ratio 0.76, 95% confidence interval [CI] 0.30-1.92). Secondary outcomes were similar in each group. Significantly higher pain scores were reported in the scratch group (adjusted mean difference 3.2, 95% CI 2.5-3.9) when measured on a visual analogue scale. CONCLUSION: No difference was detected in live birth rate for women with PCOS who received an endometrial scratch when trying to conceive using ovulation induction; however, uncertainty remains due to the small sample size in this study.

Notes on distribution of Simulium damnosum s. l. along Atbara River in Galabat sub-focus, eastern Sudan.

BACKGROUND: Onchocerciasis is caused by a nematode worm Onchocerca volvulus, which is transmitted in Sudan by black fly vectors of the Simulium damnosum sensu lato species complex. In Sudan, the disease is found in four foci where fast flowing rivers provide suitable breeding sites for the Simulium vector flies. The construction of dams and irrigation schemes for agricultural purposes has affected black fly breeding and distribution, such as in Merowe Dam in Abu-Hamed focus, where the perennially flowing water downstream of the Dam created new vector breeding sites, thereby, changing the pattern of disease transmission and creating public health problems. Based on this situation, this study was carried out to measure the effect of the Upper Atbara and Setit Dam complex on the distribution of Simulium damnosum s.l. breeding sites and on disease elimination in the Galabat sub-focus in eastern Sudan. METHODS: Aquatic stages of Simulium were collected between October and November 2009, prior to the construction of the dam complex, and again in 2013 and 2015 while the dam complex construction was ongoing. RESULTS: A total of 40 breeding sites were identified at the beginning of the study. After the construction of the dam complex in 2015, seventeen previously mapped breeding sites were inaccessible as they had been flooded by the dam complex's lake when reach its maximum size. Three species were obtained from different locations: S. damnosum s.l., S. griseicolle, and S. adersi. CONCLUSIONS: This study has shown a link between the construction of the dam complex and a reduction in the breeding sites of black fly vectors. This reduction has limited the Galabat sub-focus to a small area at the upper Atbara River which become the end of the focus. To sustain the success achieved in onchocerciasis control in the Galabat sub-focus, disease control and its vector control should be strengthened in the area cross-boarding Sudan and Ethiopia.

Exercise training reduces the acute physiological severity of post-menopausal hot flushes.

KEY POINTS: A post-menopausal hot flush consists of profuse physiological elevations in cutaneous vasodilatation and sweating that are accompanied by reduced brain blood flow. These responses can be used to objectively quantify hot flush severity. The impact of an exercise training intervention on the physiological responses occurring during a hot flush is currently unknown. In a preference-controlled trial involving 21 post-menopausal women, 16 weeks of supervised moderate intensity exercise training was found to improve cardiorespiratory fitness and attenuate cutaneous vasodilatation, sweating and the reductions in cerebral blood flow during a hot flush. It is concluded that the improvements in fitness that are mediated by 16 weeks of exercise training reduce the severity of physiological symptoms that occur during a post-menopausal hot flush. A hot flush is characterised by feelings of intense heat, profuse elevations in cutaneous vasodilatation and sweating, and reduced brain blood flow. Exercise training reduces self-reported hot flush severity, but underpinning physiological data are lacking. We hypothesised that exercise training attenuates the changes in cutaneous vasodilatation, sweat rate and cerebral blood flow during a hot flush. In a preference trial, 18 symptomatic post-menopausal women underwent a passive heat stress to induce hot flushes at baseline and follow-up. Fourteen participants opted for a 16 week moderate intensity supervised exercise intervention, while seven participants opted for control. Sweat rate, cutaneous vasodilatation, blood pressure, heart rate and middle cerebral artery velocity (MCAv) were measured during the hot flushes. Data were binned into eight equal segments, each representing 12.5% of hot flush duration. Weekly self-reported frequency and severity of hot flushes were also recorded at baseline and follow-up. Following training, mean hot flush sweat rate decreased by 0.04 mg cm(2) min(-1) at the chest (95% confidence interval 0.02-0.06, P = 0.01) and by 0.03 mg cm(2) min(-1) (0.02-0.05, P = 0.03) at the forearm, compared with negligible changes in control. Training also mediated reductions in cutaneous vasodilatation by 9% (6-12%) at the chest and by 7% (4-9%) at forearm (P ≤ 0.05). Training attenuated hot flush MCAv by 3.4 cm s(-1) (0.7-5.1 cm s(-1) , P = 0.04) compared with negligible changes in control. Exercise training reduced the self-reported severity of hot flushes by 109 arbitrary units (80-121, P < 0.001). These data indicate that exercise training leads to parallel reductions in hot flush severity and within-flush changes in cutaneous vasodilatation, sweating and cerebral blood flow.

Endothelial dysfunction in hyperandrogenic polycystic ovary syndrome is not explained by either obesity or ectopic fat deposition.

PCOS (polycystic ovary syndrome) is associated with IR (insulin resistance), increased visceral fat and NAFLD (non-alcoholic fatty liver disease) all of which may contribute to endothelial dysfunction, an early marker of CVD (cardiovascular disease) risk. Our objective was to examine the relationships between endothelial dysfunction in PCOS, the volume of AT (adipose tissue) compartments and the size of intracellular TAG (triacylglycerol) pools in liver and skeletal muscle. A total of 19 women with PCOS (means±S.D.; 26±6 years, 36±5 kg/m2) and 16 control women (31±8 years, 30±6 kg/m2) were recruited. Endothelial function was assessed in the brachial artery using FMD (flow-mediated dilation). VAT (visceral AT) and abdominal SAT (subcutaneous AT) volume were determined by whole body MRI, and liver and skeletal muscle TAG by 1H-MRS (proton magnetic resonance spectroscopy). Cardiorespiratory fitness and HOMA-IR (homoeostasis model assessment of IR) were also determined. Differences between groups were analysed using independent Student's t tests and ANCOVA (analysis of co-variance). FMD was impaired in PCOS by 4.6% [95% CI (confidence interval), 3.0-7.7; P<0.001], and this difference decreased only slightly to 4.2% (95% CI, 2.4-6.1; P<0.001) when FMD was adjusted for individual differences in visceral and SAT and HOMA-IR. This magnitude of impairment was also similar in lean and obese PCOS women. The results suggest that endothelial dysfunction in PCOS is not explained by body fat distribution or volume. FMD might be a useful independent prognostic tool to assess CVD risk in this population.

Endothelial function measured using flow-mediated dilation in polycystic ovary syndrome: a meta-analysis of the observational studies.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) demonstrate an increased prevalence of cardiovascular disease (CVD) risk factors. Previous researchers have compared flow-mediated dilation (FMD), an early marker of CVD, in women with and without PCOS. Evidence for a PCOS-mediated reduction in FMD remains equivocal, potentially because of study differences in cohort-matching and measurement approaches. The aims of this systematic review and meta-analysis were to examine to what extent FMD is impaired in PCOS and to explore the influence of potential moderators of FMD reduction, such as age and BMI. DESIGN: A systematic review and meta-analysis of published observational studies comparing FMD in PCOS with control women. PATIENTS: Twenty-one published studies were included (PCOS, n = 908; controls, n = 566). A subanalysis, using tighter inclusion criteria, involved seven studies (PCOS, n = 402; control, n = 251). MEASUREMENTS: Mean differences in FMD between PCOS and controls were synthesized. The subanalysis was delimited to the inclusion of age and BMI-matched controls. These factors were then explored as moderators using meta-regression. RESULTS: The pooled mean FMD was 3.4% (95% CI=1.9, 4.9) lower in PCOS compared with control women, with substantial heterogeneity between studies. In the subanalysis, the PCOS-mediated reduction in FMD was 4.1% (95% CI=2.7, 5.5). Heterogeneity remained substantial (I(2) =81%). Subsequent meta-regression indicated that the magnitude of FMD difference was not influenced by BMI (P = 0.17) nor age (P = 0.38). CONCLUSIONS: This systematic research synthesis indicates that endothelial function is compromised in PCOS women, even if they are young and nonobese.

Evaluating the Effects of Training to Improve Teaching Skills of Health Sciences Educators in Sudan.

Purpose: This evaluation draws evidence on the outcome of learning and teaching courses that were offered to a number of teaching staff (referred to as trainers) of the Academies of Health Sciences, Midwifery Schools and Centre for Continuous Professional Development in Sudan. Methods: The evaluation was a cross-sectional, institution-based study conducted from October 2017 to January 2018 involving qualitative design. It consisted of direct observations of teaching, focus group discussions with students and semi-structured interviews with managers of teaching institutions. Results: The findings of direct observations revealed that the learning and teaching course has positive effects on the trainers' ability to have clear, well-stated learning objectives; their presentation skills; and their use of different teaching methods. Moreover, the observations showed that trainers who attended the learning and teaching course now encourage the students to ask questions and are providing them with timely feedback about their learning. As students were the main beneficiaries for improved teaching, focus group discussions have shown that students were generally satisfied with trainers' performance regarding the stated learning outcomes, curricula design, use of a range of teaching methods and assessment methods. During in-depth interviews, managers of training institutions expressed satisfaction with the trainers' performance regarding the development of training materials, learners' assessment, supervision, and evaluation of training. Conclusion: Short courses on teaching and learning were a valuable investment for trainers, students, and the overall performance of health sciences training institutions. The evaluation revealed that trainers were able to apply what they have learnt. Moreover, students and managers noticed improvement in the performance of trainers in teaching, course delivery and assessment. It is recommended to expand, cascade and institutionalize the short courses on learning and teaching to all states to improve the capabilities of trainers, which would eventually contribute to the production of competent allied health professions in Sudan.

Piloting a trachomatous trichiasis patient case-searching approach in two localities of Sudan.

BACKGROUND: Approximately 1.9 million people have become blind or visually impaired from trachoma, the leading cause of infectious blindness. Trachoma prevalence surveys conducted in Sudan have shown that thousands of Sudanese suffer from the advanced stages of the disease, trachomatous trichiasis (TT), and warrant sight-saving surgery. Sudan's National Trachoma Control Program (NTCP) provides free TT surgery; however, given that many TT patients live in remote areas with limited access to health services, identifying patients and providing eye care services has proved challenging. For this reason, the Sudan NTCP piloted a systematic TT case-finding approach to identify patients. METHODS: In Gedarif state, 11 villages in Baladyat el Gedarif locality and 21 villages in West Galabat locality were included in a TT case-searching activity from September to November 2018. TT case finders were selected from the villages where the activity took place and were trained by ophthalmic medical assistants to identify possible patients. RESULTS: Of 66 626 villagers examined, 491 were identified as having TT by TT case finders. Of those, 369 were confirmed as true cases by the TT surgeons, a 75.2% (369/491) success rate. CONCLUSIONS: The TT case-finding approach provides an example of an effective method for identifying TT patients and should be expanded to other parts of the country known to be endemic for trachoma.

The Galabat-Metema cross-border onchocerciasis focus: The first coordinated interruption of onchocerciasis transmission in Africa.

BACKGROUND: Onchocerciasis transmission across international borders is not uncommon, yet a coordinated cross border stops mass drug administration (MDA) decision has not been documented. METHODS/PRINCIPLE FINDINGS: The Galabat-Metema focus involves neighboring districts on the border between Sudan and Ethiopia. Mass drug administration (MDA) was provided once and subsequently twice per year in this focus, with twice-per-year beginning in Ethiopia's Metema subfocus in 2016 and in the Sudan's Galabat subfocus in 2008. Ov16 ELISA-based serosurveys were conducted in 6072 children under 10 years of age in the Metema subfocus in 2014, and 3931 in the Galabat in 2015. Between 2014 and 2016, a total of 27,583 vector Simulium damnosum flies from Metema and 9,148 flies from Galabat were tested by pool screen PCR for Onchocerca volvulus O-150 DNA. Only 8 children were Ov16 seropositive (all in the Metema subfocus); all were negative by skin snip PCR. The upper limit of the 95% confidence interval (UCL) for Ov16 seropositive was <0.1% for the overall focus and 0.14 positive fly heads per 2000 (UCL = 0.39/2000). However, an entomological 'hotspot' was detected on the Wudi Gemzu river in Metema district. The hotspot was confirmed when 4 more positive fly pools were found on repeat testing in 2017 (1.04 L3/2000 flies (UCL = 2.26/2000). Information exchange between the two countries led to stopping MDA in a coordinated fashion in 2018, with the exception of the hotspot at Wudi Gemzu, where MDA with ivermectin was increased to every three months to hasten interruption of transmission. CONCLUSION: Coordinated stop MDA decisions were made by Sudan and Ethiopia based on data satisfying the World Health Organization's criteria for interruption of onchocerciasis transmission. Definitions of entomological 'hotspots' and buffer zones around the focus are proposed.

The positive influence the Onchocerciasis Elimination Program for the Americas has had on Africa programs.

A recent article "Is onchocerciasis elimination in Africa feasible by 2025: a perspective based on lessons learnt from the African control programmes" in Infectious Diseases of Poverty claimed that undue influence on African programs by concepts developed by the Onchocerciasis Elimination Program of the Americas (OEPA) is detrimental to stopping mass drug administration (MDA) in Africa. This claim is made despite a record year for MDA stoppage in four African countries of > 3.5 million treatments in 2018, far exceeding any past OEPA or African Program for Onchocerciasis Control (APOC) stop MDA success.

Progress toward Elimination of Trachoma as a Public Health Problem in Seven Localities in the Republic of Sudan: Results from Population-Based Surveys.

Trachoma is the leading cause of infectious blindness in the world. After baseline surveys demonstrated that Sudan was endemic for trachoma, the Sudan Federal Ministry of Health (FMOH) Trachoma Control Program conducted trachoma prevention and treatment interventions in endemic localities. The Sudan FMOH conducted population-based trachoma prevalence surveys between September 2016 and April 2017 in seven localities across five states of Sudan to document current trachoma prevalence estimates and measure water, sanitation, and hygiene (WASH) indicators. Children aged 1-9 years were examined for five clinical signs of trachoma, and participants of all ages were examined for trachomatous trichiasis (TT). A household questionnaire was administered to gather demographic and WASH-related information. The prevalence of trachomatous inflammation-follicular (TF) in children aged 1-9 years ranged from 0.4% (95% CI: 0.1-1.1%) to 6.4% (95% CI: 3.3-11.9%). Trachomatous trichiasis in those aged 15 years and older ranged from 0.1% (95% CI: 0.0-0.6%) to a high of 4.4% (95% CI: 2.1-9.1%). Of seven localities surveyed, four localities had achieved the elimination threshold of less than 5% TF in children aged 1-9 years. Six localities still required interventions to achieve less than 0.2% TT in those aged 15 years and older. The presence of latrine ranged from a low of 10.8% (95% CI: 5.2-21.1%) to 88.4% (CI: 81.5-93.0%) and clean face among children ranged between 69.5% (95% CI: 63.5-75.0%) and 87.5% (95% CI: 81.2-91.9%). These results demonstrate that Sudan is within reach of eliminating trachoma as a public health problem.

Prevalence of trachoma within refugee camps serving South Sudanese refugees in White Nile State, Sudan: Results from population-based surveys.

BACKGROUND: The world is witnessing mass displacement of populations which could impact global efforts to eliminate neglected tropical diseases such as trachoma. On the African continent, South Sudan has experienced high levels of population displacement. Population based baseline trachoma surveys were conducted among refugee camps in two Sudanese localities hosting South Sudanese refugee populations to determine whether the SAFE strategy was warranted. METHODOLOGY/PRINCIPAL FINDINGS: Cross-sectional, multi-stage, cluster-random surveys were conducted within refugee camps in each of two Sudanese localities, Al Salam and Al Jabalain. For survey sampling, multiple camps within each locality were combined to form the sampling frame for that locality. Household water, sanitation and hygiene indicators were assessed, and trachoma signs were graded by trained and certified graders. The prevalence of trachomatous inflammation-follicular (TF) in children aged one to nine years was 15.7% (95%CI: 12.1-20.2) in Al Salam and 10.6% (95%CI: 7.9-14.0) in Al Jabalain. The prevalence of trachomatous trichiasis (TT) in those 15 years above was 2.9% (95%CI: 1.8-4.8) in Al Salam and 5.0% (95%CI: 3.8-6.6) in Al Jabalain. The presence of water and sanitation was high in both survey units. CONCLUSION/ SIGNIFICANCE: Sudan has made progress in reducing the prevalence of trachoma within the country; however, the presence of over one million refugees from a neighboring trachoma hyper-endemic country could impact this progress. These surveys were the first step in addressing this important issue. The results demonstrate that at least three years of mass drug administration with azithromycin and tetracycline is needed in addition to the provision of TT surgical services. Additionally, it highlights that non-endemic or formerly endemic localities may have to adopt new strategies to provide services for refugee populations originating from hyper-endemic regions to ensure elimination of trachoma as a public health problem for all populations.

Operational Performance of the Onchocerca volvulus "OEPA" Ov16 ELISA Serological Assay in Mapping, Guiding Decisions to Stop Mass Drug Administration, and Posttreatment Surveillance Surveys.

Onchocerciasis is a neglected tropical disease targeted for elimination. The World Health Organization (WHO) has developed guidelines for the verification of onchocerciasis elimination that include entomological and epidemiological criteria. The latter require demonstrating with statistical confidence that the infection prevalence in children is less than 0.1%, necessitating an assay with a high degree of specificity. We present an analysis of the performance of the Onchocerciasis Elimination Program for the Americas (OEPA) version of the Ov16 enzyme-linked immunosorbant assay (ELISA) when used under operational conditions. In Africa and Latin America, the assay demonstrated 99.98% specificity in 69,888 children in 20 foci where transmission was believed to be interrupted. The assay produced a prevalence estimate equal to that of skin snip microscopy when applied in putatively hypo-endemic zones of Ethiopia. The OEPA Ov16 ELISA demonstrated the specificity required to be effectively deployed to verify transmission elimination under the WHO guidelines, while exhibiting a sensitivity equivalent to skin snip microscopy to identify hypo-endemic areas.

Stool antigen detection versus 13C-urea breath test for non-invasive diagnosis of pediatric Helicobacter pylori infection in a limited resource setting.

INTRODUCTION: The prevalence of childhood infection with Helicobacter pylori is high, especially in developing countries. Non-invasive methods for detection of infection in children should be inexpensive, easy to perform, well tolerated and have a high diagnostic accuracy. We aimed to compare the reliability, specificity and sensitivity of the H. pylori stool antigen (HpSA) test with the 13C-urea breath test (13C-UBT) for the diagnosis of H. pylori infection in a limited resource setting. MATERIAL AND METHODS: The stool samples of 60 symptomatic and dyspeptic children with a mean age of 7.2 ±3.7 years (2-15 years) were evaluated using the rapid One step HpSA test by lateral flow immunoassay. The 13C-UBT was used as the gold standard method for the diagnosis of H. pylori infection. RESULTS: The HpSA test detected H. pylori antigen in 34 out of 38 positive patients with 4 false-negatives (sensitivity 89.5%, 95% confidence interval (CI): 75.2-97.1%), while 21 patients had true-negative results and one false-positive (specificity 95.5%, 95% CI: 77.2-99.9%), with a strong measure of agreement between the HpSA test and the 13C-UBT (κ = 0.83, 95% CI: 68-97%, p < 0.001). It had a positive predictive value of 97.1% (95% CI: 85.1-99.9%), a negative predictive value of 84% (95% CI: 63.9-95.5%) and an accuracy of 91.7%. CONCLUSIONS: The rapid lateral flow HpSA test is a reliable method for the primary diagnosis of H. pylori infections in children, though not as accurate as the 13C-UBT. It is more affordable, simpler to perform and more tolerable, representing a viable alternative, especially in developing countries.

The Forgotten YY2 in Reported YY1 Expression Levels in Human Cancers.

The transcription factor Yin Yang 1 (YY1) has been reported to be overexpressed in the majority of human cancers and that overexpression has prognostic significance. YY1 regulates several properties associated with cancer cells, including cell survival, cell proliferation, endothelial-mesenchymal transition, metastases, and resistance to both chemotherapeutics and immunotherapeutics. Although the majority of published reports focus on YY1 levels, little has been reported on the expression and activity of YY1 family member Yin Yang 2 (YY2). YY1 and YY2 share more than 50% homologies in DNA and amino acid sequences and share the same C-terminal zinc finger domains involved in DNA binding. This survey of the reported literature revealed that the antibodies used in published immunohistochemistry analyses were not uniquely specific for YY1. Most were likely cross-reactive with YY2. Furthermore, data from the Human Protein Atlas regarding YY1 and YY2 expression in various cancers were generated using antibodies that did not discriminate between YY1 and YY2. This review analyzed the commercially available antibodies listed against YY1 and YY2 and determined their cross-reactivities. A summary is of the published studies on the expression levels of YY1 in human cancers and their potential cross-reactivities with YY2 is also provided. Well-documented monospecific antibodies to both YY1 and YY2 have to be developed and used when examining the expression levels of YY1 and YY2 in human cancers to elucidate the accurate relationship between them and clinical significance of each.

Activation of Natural Killer Cells by Probiotics.

During the last decade, probiotics have been established to be important mediators of host immunity. Their effects on both innate and adaptive immunity have been documented in the literature. Although several reports have correlated different strains of bacteria as probiotics, their effects on immunity vary. Clearly, there is a complex interplay between various constituents of probiotics and the immune response in humans. The role of probiotics on natural killer (NK) cells in the gut has been the subject of a few reports. In this review, we summarize the reported findings on the role of probiotics in the activation of gut-associated NK cells and the response of NK cells to stimuli elicited by probiotics and their microenvironment. The effects of probiotics on the activation of NK cells and their secretion of immune factors (e.g., interferon-γ, tumor necrosis factor-α, interleukin-2, etc.) are discussed in regard to their clinical significance in various diseases. Current investigations are being pursued, in particular, on the role of probiotics-activated NK cells in promoting the adaptive immune response against pathogens.

Exercise training reduces the frequency of menopausal hot flushes by improving thermoregulatory control.

OBJECTIVE: Postmenopausal hot flushes occur due to a reduction in estrogen production causing thermoregulatory and vascular dysfunction. Exercise training enhances thermoregulatory control of sweating, skin and brain blood flow. We aimed to determine if improving thermoregulatory control and vascular function with exercise training alleviated hot flushes. METHODS: Twenty-one symptomatic women completed a 7-day hot flush questionnaire and underwent brachial artery flow-mediated dilation and a cardiorespiratory fitness test. Sweat rate and skin blood flow temperature thresholds and sensitivities, and middle cerebral artery velocity (MCAv) were measured during passive heating. Women performed 16 weeks of supervised exercise training or control, and measurements were repeated. RESULTS: There was a greater improvement in cardiorespiratory fitness (4.45 mL/kg/min [95% CI: 1.87, 8.16]; P = 0.04) and reduced hot flush frequency (48 hot flushes/wk [39, 56]; P < 0.001) after exercise compared with control. Exercise reduced basal core temperature (0.14°C [0.01, 0.27]; P = 0.03) and increased basal MCAv (2.8 cm/s [1.0, 5.2]; P = 0.04) compared with control. Sweat rate and skin blood flow thresholds occurred approximately 0.19°C and 0.17°C earlier, alongside improved sweating sensitivity with exercise. MCAv decreased during heating (P < 0.005), but was maintained 4.5 cm/s (3.6, 5.5; P < 0.005) higher during heating after exercise compared with control (0.6 cm/s [-0.4, 1.4]). CONCLUSIONS: Exercise training that improves cardiorespiratory fitness reduces self-reported hot flushes. Improvements are likely mediated through greater thermoregulatory control in response to increases in core temperature and enhanced vascular function in the cutaneous and cerebral circulations.

Seasonal Variation in Biting Rates of Simulium damnosum sensu lato, Vector of Onchocerca volvulus, in Two Sudanese Foci.

BACKGROUND: The abundance of onchocerciasis vectors affects the epidemiology of disease in Sudan, therefore, studies of vector dynamics are crucial for onchocerciasis control/elimination programs. This study aims to compare the relative abundance, monthly biting-rates (MBR) and hourly-based distribution of onchocerciasis vectors in Abu-Hamed and Galabat foci. These seasonally-based factors can be used to structure vector control efforts to reduce fly-biting rates as a component of onchocerciasis elimination programs. METHODS: A cross-sectional study was conducted in four endemic villages in Abu-Hamed and Galabat foci during two non-consecutive years (2007-2008 and 2009-2010). Both adults and aquatic stages of the potential onchocerciasis vector Simulium damnosum sensu lato were collected following standard procedures during wet and dry seasons. Adult flies were collected using human landing capture for 5 days/month. The data was recorded on handheld data collection sheets to calculate the relative abundance, MBR, and hourly-based distribution associated with climatic factors. The data analysis was carried out using ANOVA and Spearman rank correlation tests. RESULTS: Data on vector surveillance revealed higher relative abundance of S. damnosum s.l. in Abu- Hamed (39,934 flies) than Galabat (8,202 flies). In Abu-Hamed, vector populations increased in January-April then declined in June-July until they disappeared in August-October. Highest black fly density and MBR were found in March 2007 (N = 9,444, MBR = 58,552.8 bites/person/month), and March 2010 (N = 2,603, MBR = 16,138.6 bites/person/month) while none of flies were collected in August-October (MBR = 0 bites/person/month). In Galabat, vectors increased in September-December, then decreased in February-June. The highest vector density and MBR were recorded in September 2007 (N = 1,138, MBR = 6,828 bites/person/month) and September 2010 (N = 1,163, MBR = 6,978 bites/person/month), whereas, none appeared in collection from April to June. There was a significant difference in mean monthly density of S. damnosum s.l. across the two foci in 2007-2008 (df = 3, F = 3.91, P = 0.011). Minimum temperature showed significant correlation with adult flies counts in four areas sampled; the adult counts were increased in Nady village (rs = 0.799) and were decreased in Kalasecal (rs = -0.676), Gumaiza (rs = -0.585), and Hilat Khateir (rs = -0.496). Maximum temperature showed positive correlation with black fly counts only in Galabat focus. Precipitation was significantly correlated with adult flies counts in Nady village, Abu-Hamed, but no significance was found in the rest of the sampled villages in both foci. Hourly-based distribution of black flies showed a unimodal pattern in Abu-Hamed with one peak (10:00-18:00), while a bimodal pattern with two peaks (07:00-10:00) and (14:00-18:00) was exhibited in Galabat. CONCLUSION: Transmission of onchocerciasis in both foci showed marked differences in seasonality, which may be attributed to ecology, microclimate and proximity of breeding sites to collection sites. The seasonal shifts between the two foci might be related to variations in climate zones. This information on black fly vector seasonality, ecology, distribution and biting activity has obvious implications in monitoring transmission levels to guide the national and regional onchocerciasis elimination programs in Sudan.

The First Confirmed Elimination of an Onchocerciasis Focus in Africa: Abu Hamed, Sudan.

Mass treatment with ivermectin for onchocerciasis was stopped in 2012 in Abu Hamed, an isolated focus on the River Nile in northern Sudan. A 3-year posttreatment surveillance (PTS) ensued, at the end of which an evaluation was conducted in 2015 following the current World Health Organization guidelines for verification of onchocerciasis elimination. Vector black flies were collected from sentinel breeding sites and finger-prick bloodspots were collected from children ≤ 10 years of age resident in 35 communities within the focus. Polymerase chain reaction (PCR) screening of 19,191 flies from four sites for the O-150 parasite-specific marker found no flies carrying Onchocerca volvulus larvae (0%, 95% upper confidence limit [UCL] = 0.16), and serological testing of 5,266 children identified only one Ov16 seropositive child (0.019%, 95% UCL = 0.074); whose skin snips were negative when tested by O-150 PCR assay. These results indicate that for the first time in Africa, onchocerciasis elimination has been verified after a successful PTS in Abu Hamed.

Novel association between sperm deformity index and oxidative stress-induced DNA damage in infertile male patients.

AIM: To investigate the impact of abnormal sperm morphology using the sperm deformity index (SDI) on reactive oxygen species (ROS) production and its correlation with sperm DNA damage. METHODS: Semen samples were collected from men undergoing infertility screening (n = 7) and healthy donors (n = 6). Mature spermatozoa were isolated and incubated with 5 mmol/L beta-nicotinamide adenine dinucleotide phosphate (NADPH) for up to 24 h to induce ROS. Sperm morphology was evaluated using strict Tygerberg's criteria and the SDI. ROS levels and DNA damage were assessed using chemiluminescence and terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling (TUNEL) assays, respectively. RESULTS: SDI values (median [interquartiles]) were higher in patients than donors (2 [1.8, 2.1] vs. 1.53 [1.52, 1.58], P = 0.008). Aliquots treated with NADPH showed higher ROS levels (1.22 [0.30, 1.87] vs. 0.39 [0.10, 0.57], P = 0.03) and higher incidence of DNA damage than those not treated (10 [4.69, 24.85] vs. 3.85 [2.58, 5.10], P = 0.008). Higher DNA damage was also seen following 24 h of incubation in patients compared to donors. SDI correlated with the percentage increase in sperm DNA damage following incubation for 24 h in samples treated with NADPH (r = 0.7, P = 0.008) and controls (r = 0.58, P = 0.04). CONCLUSION: SDI may be a useful tool in identifying potential infertile males with abnormal prevalence of oxidative stress (OS)-induced DNA damage. NADPH plays a role in ROS-mediated sperm DNA damage, which appears to be more evident in infertile patients with semen samples containing a high incidence of morphologically abnormal spermatozoa.

Sperm chromosomal abnormalities are linked to sperm morphologic deformities.

OBJECTIVE: To describe the association between specific sperm morphologic abnormalities and sperm chromosomal abnormalities on multicolor interphase fluorescence in situ hybridization (FISH). DESIGN: Case report. Reproductive medicine unit in a tertiary referral center. PATIENT(S): Three infertile men with severe oligoasthenospermia and total teratozoospermia who were referred for IVF treatment. MAIN OUTCOME MEASURE(S): Incidence of spermatozoal chromosomal aneuploidy for chromosome 18 and the sex chromosomes by using FISH. RESULT(S): Morphologic assessment of sperm revealed a high incidence of double heads, multinucleated sperm heads, and multiple tails. Hormone profiles and karyotyping of peripheral lymphocytes were normal in the three men. The proportion of sperm with disomy, trisomy and tetrasomy for chromosome 18, and the sex chromosomes in each patient was 100%, 76%, and 82.5%, respectively. CONCLUSION(S): Specific morphologic abnormalities of sperm may be associated with higher incidence of chromosomal abnormalities. Resolving infertility by offering patients in vitro fertilization/intracytoplasmic sperm injection must be approached with caution because of the significant risk for embryonic aneuploidy and chromosomal abnormalities in any subsequent offspring.