National Survey Highlights the Urgent Need for Standardisation of Embryo Transfer Techniques in the UK

Embryo transfer (ET) is one of the vital steps in the in vitro fertilisation (IVF) process, yet there is wide variation in ET technique throughout the UK, without a nationally approved standardised approach. The aim of this study was to gain contemporaneous information regarding the current clinical ET practice in the UK. Method: A 38-question electronic survey was distributed to the 79 UK Human Fertilisation and Embryology Authority (HFEA) registered clinics performing ETs. Results: In total, 59% (47/79) of units responded, 83% (39/47) performing ultrasound-guided transfers, with 42% (20/47) of units using a tenaculum; 22% (10/45) would proceed with transfer regardless of fluid in the endometrial cavity. In 91% (43/47) of units, embryos were deposited in the upper/middle portion of the uterine cavity, but interpretation of this area ranged from 0.5 to >2 cm from the fundus, with 68% (32/47) allowing patients to mobilise immediately after transfer. In 60% (27/45) of clinics, success rates were based on clinical pregnancy rates (CPR). Conclusion: Within the UK there is a wide range of variability in ET techniques, with >70% of discordance in survey-responses between clinics. Whilst there are areas of good practice, some disadvantageous techniques continue to persist. This survey emphasises the importance of developing a standardised, evidence-based approach to improve ET success rates

Malaria morbidity and immunity among residents of villages with different Plasmodium falciparum transmission intensity in North-Eastern Tanzania

BACKGROUND: The relationship between the burden of uncomplicated malaria and transmission intensity is unclear and a better understanding of this relationship is important for the implementation of intervention programmes. METHODS: A 6-month longitudinal study monitoring risk factors for anaemia and febrile malaria episodes was conducted among individuals aged below 20 years, residing in three villages of different altitude in areas of high, moderate and low malaria transmission intensity in North-Eastern Tanzania. RESULTS: The burden of anaemia and malarial fever fell mainly on the youngest children and was highest in the village with high transmission intensity. Although a considerable percentage of individuals in all villages carried intestinal worms, logistic regression models indicated that Plasmodium falciparum was the only significant parasitic determinant of anaemia. Interestingly, children who carried low-density parasitaemia at the start of the study had a lower risk of contracting a febrile malaria episode but a higher risk of anaemia during the study period, than children who were slide negative at this point in time. CONCLUSION: Young children living in the high transmission village carried a very high anaemia burden, which could be attributed to malaria. The overall incidence of febrile malaria was also highest in the high transmission village particularly among those under five years of age. These data suggest that in rolling back malaria, available resources in prevention programmes should primarily be focussed on young children, particularly those residing in areas of high malaria transmission

Defining the geographical range of the plasmodium knowlesi reservoir

Background: The simian malaria parasite, Plasmodium knowlesi, can cause severe and fatal disease in humans yet it is rarely included in routine public health reporting systems for malaria and its geographical range is largely unknown. Because malaria caused by P. knowlesi is a truly neglected tropical disease, there are substantial obstacles to defining the geographical extent and risk of this disease. Information is required on the occurrence of human cases in different locations, on which non-human primates host this parasite and on which vectors are able to transmit it to humans. We undertook a systematic review and ranked the existing evidence, at a subnational spatial scale, to investigate the potential geographical range of the parasite reservoir capable of infecting humans.Methodology/Principal Findings: After reviewing the published literature we identified potential host and vector species and ranked these based on how informative they are for the presence of an infectious parasite reservoir, based on current evidence. We collated spatial data on parasite occurrence and the ranges of the identified host and vector species. The ranked spatial data allowed us to assign an evidence score to 475 subnational areas in 19 countries and we present the results on a map of the Southeast and South Asia region.Conclusions/Significance: We have ranked subnational areas within the potential disease range according to evidence for presence of a disease risk to humans, providing geographical evidence to support decisions on prevention, management and prophylaxis. This work also highlights the unknown risk status of large parts of the region. Within this unknown category, our map identifies which areas have most evidence for the potential to support an infectious reservoir and are therefore a priority for further investigation. Furthermore we identify geographical areas where further investigation of putative host and vector species would be highly informative for the region-wide assessment

Associations between red blood cell variants and malaria among children and adults from three areas of Uganda: a prospective cohort study.

BACKGROUND: Multiple red blood cell (RBC) variants appear to offer protection against the most severe forms of Plasmodium falciparum malaria. Associations between these variants and uncomplicated malaria are less clear. METHODS: Data from a longitudinal cohort study conducted in 3 sub-counties in Uganda was used to quantify associations between three red blood cell variants Hb [AA, AS, S (rs334)], alpha thalassaemia 3.7 kb deletion, and glucose-6-phosphate dehydrogenase deficiency A-(G6PD 202A genotype) and malaria incidence, parasite prevalence, parasite density (a measure of anti-parasite immunity) and body temperature adjusted for parasite density (a measure of anti-disease immunity). All analyses were adjusted for age, average household entomological inoculation rate, and study site. Results for all variants were compared to those for wild type genotypes. RESULTS: In children, HbAS was associated, compared to wild type, with a lower incidence of malaria (IRR = 0.78, 95% CI 0.66-0.92, p = 0.003), lower parasite density upon infection (PR = 0.66, 95% CI 0.51-0.85, p = 0.001), and lower body temperature for any given parasite density (- 0.13 ℃, 95% CI - 0.21, - 0.05, p = 0.002). In children, HbSS was associated with a lower incidence of malaria (IRR = 0.17, 95% CI 0.04-0.71, p = 0.02) and lower parasite density upon infection (PR = 0.31, 95% CI 0.18-0.54, p < 0.001). α-/αα thalassaemia, was associated with higher parasite prevalence in both children and adults (RR = 1.23, 95% CI 1.06-1.43, p = 0.008 and RR = 1.52, 95% CI 1.04-2.23, p = 0.03, respectively). G6PD deficiency was associated with lower body temperature for any given parasite density only among male hemizygote children (- 0.19 ℃, 95% CI - 0.31, - 0.06, p = 0.003). CONCLUSION: RBC variants were associated with non-severe malaria outcomes. Elucidation of the mechanisms by which they confer protection will improve understanding of genetic protection against malaria

Plasmodium vivax transmission in Africa

Malaria in sub-Saharan Africa has historically been almost exclusively attributed to Plasmodium falciparum (Pf). Current diagnostic and surveillance systems in much of sub-Saharan Africa are not designed to identify or report non-Pf human malaria infections accurately, resulting in a dearth of routine epidemiological data about their significance. The high prevalence of Duffy negativity provided a rationale for excluding the possibility of Plasmodium vivax (Pv) transmission. However, review of varied evidence sources including traveller infections, community prevalence surveys, local clinical case reports, entomological and serological studies contradicts this viewpoint. Here, these data reports are weighted in a unified framework to reflect the strength of evidence of indigenous Pv transmission in terms of diagnostic specificity, size of individual reports and corroboration between evidence sources. Direct evidence was reported from 21 of the 47 malaria-endemic countries studied, while 42 countries were attributed with infections of visiting travellers. Overall, moderate to conclusive evidence of transmission was available from 18 countries, distributed across all parts of the continent. Approximately 86.6 million Duffy positive hosts were at risk of infection in Africa in 2015. Analysis of the mechanisms sustaining Pv transmission across this continent of low frequency of susceptible hosts found that reports of Pv prevalence were consistent with transmission being potentially limited to Duffy positive populations. Finally, reports of apparent Duffy-independent transmission are discussed. While Pv is evidently not a major malaria parasite across most of sub-Saharan Africa, the evidence presented here highlights its widespread low-level endemicity. An increased awareness of Pv as a potential malaria parasite, coupled with policy shifts towards species-specific diagnostics and reporting, will allow a robust assessment of the public health significance of Pv, as well as the other neglected non-Pf parasites, which are currently invisible to most public health authorities in Africa, but which can cause severe clinical illness and require specific control intervention

Using serological measures to monitor changes in malaria transmission in Vanuatu

BACKGROUND: With renewed interest in malaria elimination, island environments present unique opportunities to achieve this goal. However, as transmission decreases, monitoring and evaluation programmes need increasingly sensitive tools to assess Plasmodium falciparum and Plasmodium vivax exposure. In 2009, to assess the role of serological markers in evaluating malaria transmission, a cross-sectional seroprevalence study was carried out in Tanna and Aneityum, two of the southernmost islands of the Vanuatu archipelago, areas where malaria transmission has been variably reduced over the past few decades. METHODS: Malaria transmission was assessed using serological markers for exposure to P. falciparum and P. vivax. Filter blood spot papers were collected from 1,249 people from Tanna, and 517 people from Aneityum to assess the prevalence of antibodies to two P. falciparum antigens (MSP-119 and AMA-1) and two P. vivax antigens (MSP-119 and AMA-1). Age-specific prevalence was modelled using a simple catalytic conversion model based on maximum likelihood to generate a community seroconversion rate (SCR). RESULTS: Overall seropositivity in Tanna was 9.4%, 12.4% and 16.6% to P. falciparum MSP-119, AMA-1 and Schizont Extract respectively and 12.6% and 15.0% to P. vivax MSP-119 and AMA-1 respectively. Serological results distinguished between areas of differential dominance of either P. vivax or P. falciparum and analysis of age-stratified results showed a step in seroprevalence occurring approximately 30 years ago on both islands, indicative of a change in transmission intensity at this time. Results from Aneityum suggest that several children may have been exposed to malaria since the 2002 P. vivax epidemic. CONCLUSION: Seroepidemiology can provide key information on malaria transmission for control programmes, when parasite rates are low. As Vanuatu moves closer to malaria elimination, monitoring changes in transmission intensity and identification of residual malaria foci is paramount in order to concentrate intervention efforts

Marked variation in MSP-119 antibody responses to malaria in western Kenyan highlands

<p>Abstract</p> <p>Background</p> <p>Assessment of malaria endemicity at different altitudes and transmission intensities, in the era of dwindling vector densities in the highlands, will provide valuable information for malaria control and surveillance. Measurement of serum anti-malarial antibodies is a useful marker of malaria exposure that indicates long-term transmission potential. We studied the serologic evidence of malaria endemicity at two highland sites along a transmission intensity cline. An improved understanding of the micro-geographic variation in malaria exposure in the highland ecosystems will be relevant in planning effective malaria control.</p> <p>Methods</p> <p>Total IgG levels to <it>Plasmodium falciparum </it>MSP-1₁₉were measured in an age-stratified cohort (< 5, 5-14 and ≥ 15 years) in 795 participants from an uphill and valley bottom residents during low and high malaria transmission seasons. Antibody prevalence and level was compared between different localities. Regression analysis was performed to examine the association between antibody prevalence and parasite prevalence. Age-specific MSP-1₁₉seroprevalence data was fitted to a simple reversible catalytic model to investigate the relationship between parasite exposure and age.</p> <p>Results</p> <p>Higher MSP-1₁₉seroprevalence and density were observed in the valley residents than in the uphill dwellers. Adults (> 15 years) recorded high and stable immune response in spite of changing seasons. Lower responses were observed in children (≤ 15 years), which, fluctuated with changing seasons particularly in the valley residents. In the uphill population, annual seroconversion rate (SCR) was 8.3% and reversion rate was 3.0%, with seroprevalence reaching a plateau of 73.3% by age of 20. Contrary, in the valley bottom population, the annual SCR was 35.8% and the annual seroreversion rate was 3.5%, and seroprevalence in the population had reached 91.2% by age 10.</p> <p>Conclusion</p> <p>The study reveals the micro-geographic variation in malaria endemicity in the highland eco-system; this validates the usefulness of sero-epidemiological tools in assessing malaria endemicity in the era of decreasing sensitivity of conventional tools.</p

Identification of malaria transmission and epidemic hotspots in the western Kenya highlands: its application to malaria epidemic prediction

<p>Abstract</p> <p>Background</p> <p>Malaria in the western Kenya highlands is characterized by unstable and high transmission variability which results in epidemics during periods of suitable climatic conditions. The sensitivity of a site to malaria epidemics depends on the level of immunity of the human population. This study examined how terrain in the highlands affects exposure and sensitivity of a site to malaria.</p> <p>Methods</p> <p>The study was conducted in five sites in the western Kenya highlands, two U-shaped valleys (Iguhu, Emutete), two V-shaped valleys (Marani, Fort-Ternan) and one plateau (Shikondi) for 16 months among 6-15 years old children. Exposure to malaria was tested using circum-sporozoite protein (CSP) and merozoite surface protein (MSP) immunochromatographic antibody tests; malaria infections were tested by microscopic examination of thick and thin smears, the children's homes were georeferenced using a global positioning system. Paired t-test was used to compare the mean prevalence rates of the sites, K-function was use to determine if the clustering of malaria infections was significant.</p> <p>Results and Discussion</p> <p>The mean antibody prevalence was 22.6% in Iguhu, 24% in Emutete, 11.5% in Shikondi, 8.3% in Fort-Ternan and 9.3% in Marani. The mean malaria infection prevalence was 23.3% in Iguhu, 21.9% in Emutete, 4.7% in Shikondi, 2.9% in Fort-Ternan and 2.4% in Marani. There was a significant difference in the antibodies and malaria infection prevalence between the two valley systems, and between the two valley systems and the plateau (P < 0.05). There was no significant difference in the antibodies and malaria infection prevalence in the two U-shaped valleys (Iguhu and Emutete) and in the V-shaped valleys (Marani and Fort Ternan) (P > 0.05). There was 8.5- fold and a 2-fold greater parasite and antibody prevalence respectively, in the U-shaped compared to the V-shaped valleys. The plateau antibody and parasite prevalence was similar to that of the V-shaped valleys. There was clustering of malaria antibodies and infections around flat areas in the U-shaped valleys, the infections were randomly distributed in the V-shaped valleys and less clustered at the plateau.</p> <p>Conclusion</p> <p>This study showed that the V-shaped ecosystems have very low malaria prevalence and few individuals with an immune response to two major malaria antigens and they can be considered as epidemic hotspots. These populations are at higher risk of severe forms of malaria during hyper-transmission seasons. The plateau ecosystem has a similar infection and immune response to the V-shaped ecosystems. The U-shaped ecosystems are transmission hotspots.</p

Clinical malaria case definition and malaria attributable fraction in the highlands of western Kenya

BACKGROUND: In African highland areas where endemicity of malaria varies greatly according to altitude and topography, parasitaemia accompanied by fever may not be sufficient to define an episode of clinical malaria in endemic areas. To evaluate the effectiveness of malaria interventions, age-specific case definitions of clinical malaria needs to be determined. Cases of clinical malaria through active case surveillance were quantified in a highland area in Kenya and defined clinical malaria for different age groups. METHODS: A cohort of over 1,800 participants from all age groups was selected randomly from over 350 houses in 10 villages stratified by topography and followed for two-and-a-half years. Participants were visited every two weeks and screened for clinical malaria, defined as an individual with malaria-related symptoms (fever [axillary temperature ≥ 37.5°C], chills, severe malaise, headache or vomiting) at the time of examination or 1–2 days prior to the examination in the presence of a Plasmodium falciparum positive blood smear. Individuals in the same cohort were screened for asymptomatic malaria infection during the low and high malaria transmission seasons. Parasite densities and temperature were used to define clinical malaria by age in the population. The proportion of fevers attributable to malaria was calculated using logistic regression models. RESULTS: Incidence of clinical malaria was highest in valley bottom population (5.0% cases per 1,000 population per year) compared to mid-hill (2.2% cases per 1,000 population per year) and up-hill (1.1% cases per 1,000 population per year) populations. The optimum cut-off parasite densities through the determination of the sensitivity and specificity showed that in children less than five years of age, 500 parasites per μl of blood could be used to define the malaria attributable fever cases for this age group. In children between the ages of 5–14, a parasite density of 1,000 parasites per μl of blood could be used to define the malaria attributable fever cases. For individuals older than 14 years, the cut-off parasite density was 3,000 parasites per μl of blood. CONCLUSION: Clinical malaria case definitions are affected by age and endemicity, which needs to be taken into consideration during evaluation of interventions

Baseline spatial distribution of malaria prior to an elimination programme in Vanuatu

BACKGROUND: The Ministry of Health in the Republic of Vanuatu has implemented a malaria elimination programme in Tafea Province, the most southern and eastern limit of malaria transmission in the South West Pacific. Tafea Province is comprised of five islands with malaria elimination achieved on one of these islands (Aneityum) in 1998. The current study aimed to establish the baseline distribution of malaria on the most malarious of the province's islands, Tanna Island, to guide the implementation of elimination activities. METHODS: A parasitological survey was conducted in Tafea Province in 2008. On Tanna Island there were 4,716 participants from 220 villages, geo-referenced using a global position system. Spatial autocorrelation in observed prevalence values was assessed using a semivariogram. Backwards step-wise regression analysis was conducted to determine the inclusion of environmental and climatic variables into a prediction model. The Bayesian geostatistical logistic regression model was used to predict malaria risk, and associated uncertainty across the island. RESULTS: Overall, prevalence on Tanna was 1.0% for Plasmodium falciparum (accounting for 32% of infections) and 2.2% for Plasmodium vivax (accounting for 68% of infections). Regression analysis showed significant association with elevation and distance to coastline for P. vivax and P. falciparum, but no significant association with NDVI or TIR. Colinearity was observed between elevation and distance to coastline with the later variable included in the final Bayesian geostatistical model for P. vivax and the former included in the final model for P. falciparum. Model validation statistics revealed that the final Bayesian geostatistical model had good predictive ability. CONCLUSION: Malaria in Tanna Island, Vanuatu, has a focal and predominantly coastal distribution. As Vanuatu refines its elimination strategy, malaria risk maps represent an invaluable resource in the strategic planning of all levels of malaria interventions for the island