Ethnic differences in metabolic syndrome in high-income countries: A systematic review and meta-analysis.

This review aimed to systematically quantify the differences in Metabolic Syndrome (MetS) prevalence across various ethnic groups in high-income countries by sex, and to evaluate the overall prevalence trends from 1996 to 2022. We conducted a systematic literature review using MEDLINE, Web of Science Core Collection, CINAHL, and the Cochrane Library, focusing on studies about MetS prevalence among ethnic groups in high-income countries. We pooled 23 studies that used NCEP-ATP III criteria and included 147,756 healthy participants aged 18 and above. We calculated pooled prevalence estimates and 95% confidence intervals (CI) using both fixed-effect and random-effect intercept logistic regression models. Data were analysed for 3 periods: 1996-2005, 2006-2009, and 2010-2021. The pooled prevalence of MetS in high-income countries, based on the NCEP-ATP III criteria, was 27.4% over the studied period, showing an increase from 24.2% in 1996-2005 to 31.9% in 2010-2021, with men and women having similar rates. When stratified by ethnicity and sex, ethnic minority women experienced the highest prevalence at 31.7%, while ethnic majority women had the lowest at 22.7%. Notably, MetS was more prevalent in ethnic minority women than men. Among ethnic minorities, women had a higher prevalence of MetS than men, and the difference was highest in Asians (about 15 percentage points). Among women, the prevalence of MetS was highest in Asians (41.2%) and lowest in Blacks/Africans (26.7%). Among men, it was highest in indigenous minority groups (34.3%) and lowest among in Blacks/Africans (19.8%). MetS is increasing at an alarming rate in high-income countries, particularly among ethnic minority women. The burden of MetS could be effectively reduced by tailoring interventions according to ethnic variations and risk profiles.

Association between antibiotic use during early life and early-onset colorectal cancer risk overall and according to polygenic risk and FUT2 genotypes.

Early-onset colorectal cancer (EOCRC) has been increasing worldwide. Potential risk factors may have occurred in childhood or adolescence. We investigated the associations between early-life factors and EOCRC risk, with a particular focus on long-term or recurrent antibiotic use (LRAU) and its interaction with genetic factors. Data on the UK Biobank participants recruited between 2006 and 2010 and followed up to February 2022 were used. We used logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) of the associations between LRAU during early life and EOCRC risk overall and by polygenic risk score (constructed by 127 CRC-related genetic variants) and Fucosyltransferase 2 (FUT2), a gut microbiota regulatory gene. We also assessed the associations for early-onset colorectal adenomas, as precursor lesion of CRC, to examine the effect of LRAU during early-life and genetic factors on colorectal carcinogenesis. A total of 113 256 participants were included in the analysis, with 165 EOCRC cases and 719 EOCRA cases. LRAU was nominally associated with increased risk of early-onset CRC (OR = 1.48, 95% CI = 1.01-2.17, P = .046) and adenomas (OR = 1.40, 95% CI = 1.17-1.68, P < .001). When stratified by genetic polymorphisms of FUT2, LRAU appeared to confer a comparatively greater risk for early-onset adenomas among participants with rs281377 TT genotype (OR = 1.10, 95% CI = 0.79-1.52, P = .587, for CC genotype; OR = 1.75, 95% CI = 1.16-2.64, P = .008, for TT genotype; Pinteraction = .089). Our study suggested that LRAU during early life is associated with increased risk of early-onset CRC and adenomas, and the association for adenomas is predominant among individuals with rs281377 TT/CT genotype. Further studies investigating how LRAU contributes together with genetic factors to modify EOCRC risk, particularly concerning the microbiome-related pathway underlying colorectal carcinogenesis, are warranted.

Associations of Body Mass Index at Different Ages With Early-Onset Colorectal Cancer.

BACKGROUND & AIMS: Incidence of colorectal cancer (CRC) in younger adults is increasing in many countries. Given the established association of body mass index (BMI) with CRC risk and the increasing obesity prevalence among younger generations, we aimed to evaluate the association of BMI at different ages during early adulthood with early-onset CRC. METHODS: Among 6602 patients with CRC and 7950 matched controls who were recruited in 2003-2020 in the Darmkrebs: Chancen der Verhütung durch Screening study, a population-based case-control study from Germany, 747 patients and 621 controls were younger than 55 years and included in this analysis. Self-reported height and weight at ages 20 years and 30 years and at approximately 10 years before diagnosis or interview were recorded in personal interviews. Associations of BMI with early-onset CRC were estimated using multiple logistic regression. RESULTS: Compared with participants with BMI <25 kg/m2, those with BMI ≥30 kg/m2 (obesity) at ages 20 years and 30 years and approximately 10 years before diagnosis or interview had 2.56- (95% confidence interval, 1.20-5.44), 2.06- (confidence interval, 1.25-3.40), and 1.88- (95% confidence interval, 1.30-2.73) fold risk of early-onset CRC. The association of BMI with early-onset CRC risk was particularly pronounced among, and essentially restricted to, the majority of participants with no previous colonoscopy. CONCLUSIONS: Obesity at early adulthood is strongly associated with increased risk of early-onset CRC. German Clinical Trials Register ID: DRKS00011793.

Global distribution, risk factors, and recent trends for cervical cancer: A worldwide country-level analysis.

OBJECTIVES: This study aimed to evaluate the most updated worldwide distribution, risk factors, and temporal trends of cervical cancer for different countries and age groups. METHODS: The Global Cancer Observatory database was retrieved for the age-standardized rates (ASRs, per 100,000 persons) for incidence and mortality of cervical cancer in 2018. The associations with risk factors were examined by multivariable regression analysis, adjusting for human development index (HDI) and gross domestic products (GDP) per capita. Joinpoint regression analysis was used to calculate the 10-year annual average percent change (AAPC) for incidence and mortality. RESULTS: A total of 568,847 new cases (ASR, 13.1) and 311,365 deaths (ASR, 6.9) of cervical cancer were reported globally in 2018. The highest incidence and mortality were observed in Southern Africa (ASRs, 43.1 and 20.0) and countries with low HDI (ASRs, 29.8 and 23.0). Countries with higher incidence and mortality had lower HDI (ß = -8.19, 95% CI -11.32 to -5.06, p < 0.001; ß = -7.66, CI -9.82 to -5.50; p < 0.001) but higher alcohol consumption (ß = 1.89, 95% CI 0.59 to 3.19, p = 0.005; ß = 0.98, CI 0.08 to 1.88; p = 0.033). An increasing trend of incidence was also observed in younger populations, with Cyprus (AAPC, 6.96), Sweden (AAPC, 4.88), and Norway (AAPC, 3.80) showing the most prominent. CONCLUSIONS: The burden of cervical cancer was highest in regions with low and medium HDI and was associated with higher prevalence of alcohol consumption. There was an overall decreasing burden of cervical cancer; however, an increase in incidence and mortality was observed in some populations. More intensive preventive strategies are recommended for these populations.

Association of Body Mass Index With Risk of Early-Onset Colorectal Cancer: Systematic Review and Meta-Analysis.

INTRODUCTION: Incidence of colorectal cancer (CRC) in young adults has been increasing in recent decades in many countries for still widely unclear reasons. Suspected candidates include increasing prevalence of overweight and obesity, but specific evidence on their role for early-onset CRC (EOCRC) is sparse. We conducted a systematic review and meta-analysis to summarize available evidence on the association of body mass index (BMI) with EOCRC. METHODS: We systematically searched PubMed, EMBASE, and Web of Science up to February 2021 for studies that evaluated the association of BMI (before diagnosis but not near diagnosis) with CRC risk and reported specific results for EOCRC. Results from studies with similar BMI groupings were summarized in meta-analyses using random-effects models. RESULTS: Twelve studies were eligible and included. Results of 6 studies were pooled in meta-analyses, which yielded a higher risk of EOCRC for overweight and obesity (BMI ≥25 kg/m2) compared with normal weight (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.19-1.68). An increasing risk with increasing BMI was observed, with much higher risk for obesity (OR 1.88, 95% CI 1.40-2.54) than for overweight (OR 1.32, 95% CI 1.19-1.47). DISCUSSION: Obesity is a strong risk factor for EOCRC, and its increasing prevalence in younger generations is likely to substantially contribute to the increase in EOCRC. Efforts to limit the obesity epidemic in adolescents and younger adults may be crucial for reducing CRC incidence in future generations of adults.

Comorbidities, Rather Than Older Age, Are Strongly Associated With Higher Utilization of Healthcare in Colorectal Cancer Survivors.

BACKGROUND: Colorectal cancer (CRC) survivors generally have a higher healthcare utilization (HCU) than the general population due to cancer burden. However, it is unclear which factors are associated with this increased uptake. Our study aimed to (1) compare CRC-related and non-CRC visits to general practitioners (GPs) and medical specialists (MSs) by comorbidities, and (2) assess whether HCU differs by demographic, clinical, and psychological factors. METHODS: We used data from a German population-based cohort of 1,718 survivors of stage I-III CRC diagnosed in 2003 through 2010 who provided information on HCU at 5-year follow-up. Multivariable linear regression was used to calculate least-square means of CRC-related and non-CRC HCU according to the Charlson comorbidity index and comorbidity cluster, adjusting for relevant demographic, clinical, and psychological characteristics. RESULTS: A higher comorbidity level was associated with more CRC-related MS visits and non-CRC GP visits. In addition to being strongly associated with non-CRC GP visits, comorbidity clusters were associated with CRC-related GP and MS visits, but their association varied by specific cardiometabolic comorbidities. HCU was less dependent on prognostic factors for CRC, such as age and tumor stage, but was strongly associated with disease recurrence, depression, and emotional functioning. CONCLUSIONS: Comorbidities, rather than age or tumor stage, were related to HCU, suggesting that CRC survivors use healthcare mainly for reasons other than cancer 5 years postdiagnosis. Improved communication between primary and tertiary healthcare providers could enhance the medical care of cancer survivors with complex health needs and thereby also reduce healthcare costs.

Uptake Rates of Novel Therapies and Survival Among Privately Insured Versus Publicly Insured Patients With Colorectal Cancer in Germany.

BACKGROUND: In the era of personalized medicine, cancer care is subject to major changes and innovations. It is unclear, however, to what extent implementation of such innovations and their impact on patient outcomes differ by health insurance type. This study compared provision of treatment and survival outcomes among patients with colorectal cancer (CRC) who had statutory health insurance (SHI) versus private health insurance (PHI) in Germany. METHODS: We analyzed patterns of CRC treatment (surgery, chemotherapy/radiotherapy, and targeted therapy) and survival in a large cohort of patients who were diagnosed with CRC in 2003 through 2014 and were observed for an average of 6 years. Associations of type of health insurance with treatment administration and with overall, CRC-specific, and recurrence-free survival were investigated using multivariable logistic and Cox proportional hazards models, respectively. RESULTS: Of 3,977 patients with CRC, 427 (11%) had PHI. Although type of health insurance was not associated with treatment administration in patients with stage I-III disease, those with stage IV disease with PHI more often received targeted therapy (65% vs 40%; odds ratio, 2.43; 95% CI, 1.20-4.91), with differences decreasing over time because of catch-up of uptake rates in patients with SHI. Median overall survival was longer in patients with PHI than in those with SHI (137.0 vs 114.9 months; P=.010), but survival advantages were explained to a large extent by differences in sociodemographic factors. In patients with stage IV disease, survival advantages of PHI were nonsignificant and were restricted to the early years after diagnosis. CONCLUSIONS: We observed major differences in uptake of targeted therapy between patients with PHI and those with SHI but no differences in patient survival after adjusting for relevant sociodemographic, clinical, and tumor characteristics. Further studies are needed on factors associated with the uptake of therapeutic innovations and their impact on patient survival by health insurance type.

Changes in health-related outcomes among colorectal cancer patients undergoing inpatient rehabilitation therapy: a systematic review of observational and interventional studies.

BACKGROUND: Colorectal cancer (CRC) and its treatment can lead to several physical and psychosocial impairments. Cancer rehabilitation aims to reduce morbidity and improve quality of life. The objective of this review was to summarize and evaluate evidence on changes in health-related outcomes among CRC patients undergoing inpatient rehabilitation therapy and on the effectiveness of such treatment. MATERIAL AND METHODS: We conducted a systematic literature search including the electronic databases Pubmed and Web of Science to find observational and interventional studies, which investigated changes in health-related outcomes among CRC patients undergoing multidisciplinary inpatient rehabilitation programs or treatment effects. Study findings were synthesized narratively. RESULTS: Eleven studies were eligible and included in this review. Eight patient cohort studies addressed outcomes such as physical and functional status, fecal incontinence, anxiety and depression, and quality of life. Positive changes during rehabilitation therapy were observed for physical health (functional and physical status, fecal incontinence), and several dimensions of quality of life. Study findings concerning anxiety and depression were not conclusive. Studies that additionally conducted long-term follow-ups indicated that the improved health status after rehabilitative treatment waned over time. One RCT reported no effect of inpatient rehabilitation on distress and two randomized trials reported effects of exercise intensity on oxidative stress and immune response. Sample sizes were low (<100 included CRC patients) in eight studies and only the RCT included a comparison group (non-rehabilitants). CONCLUSION: The scientific evidence level was very limited. Due to the lack of a comparison group in most studies, we were only able to evaluate changes during/after inpatient rehabilitation therapy but not the effectiveness of treatment. However, study findings suggest that physical health and functional independence improve during inpatient rehabilitation, but improvements wane over time. Further large representative studies, in particular RCTs with long-term follow-up, are essential to evaluate the effectiveness of inpatient rehabilitation and identify determinants of treatment success.

Ivermectin treatment in humans for reducing malaria transmission.

BACKGROUND: Malaria is transmitted through the bite of Plasmodium-infected adult female Anopheles mosquitoes. Ivermectin, an anti-parasitic drug, acts by killing mosquitoes that are exposed to the drug while feeding on the blood of people (known as blood feeds) who have ingested the drug. This effect on mosquitoes has been demonstrated by individual randomized trials. This effect has generated interest in using ivermectin as a tool for malaria control. OBJECTIVES: To assess the effect of community administration of ivermectin on malaria transmission. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group (CIDG) Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation index - expanded, the World Health Organization (WHO) International Clinical Trials Registry Platform, ClinicalTrials.gov, and the National Institutes of Health (NIH) RePORTER database to 14 January 2021. We checked the reference lists of included studies for other potentially relevant studies, and contacted researchers working in the field for unpublished and ongoing trials. SELECTION CRITERIA: We included cluster-randomized controlled trials (cRCTs) that compared ivermectin, as single or multiple doses, with a control treatment or placebo given to populations living in malaria-endemic areas, in the context of mass drug administration. Primary outcomes were prevalence of malaria parasite infection and incidence of clinical malaria in the community. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data on the number of events and the number of participants in each trial arm at the time of assessment. For rate data, we noted the total time at risk in each trial arm. To assess risk of bias, we used Cochrane's RoB 2 tool for cRCTs. We documented the method of data analysis, any adjustments for clustering or other covariates, and recorded the estimate of the intra-cluster correlation (ICC) coefficient. We re-analysed the trial data provided by the trial authors to adjust for cluster effects. We used a Poisson mixed-effect model with small sample size correction, and a cluster-level analysis using the linear weighted model to adequately adjust for clustering.  MAIN RESULTS: We included one cRCT and identified six ongoing trials.  The included cRCT examined the incidence of malaria in eight villages in Burkina Faso, randomized to two arms. Both trial arms received a single dose of ivermectin 150 µg/kg to 200 µg/kg, together with a dose of albendazole. The villages in the intervention arm received an additional five doses of ivermectin, once every three weeks. Children were enrolled into an active cohort, in which they were repeatedly screened for malaria infection.  The primary outcome was the cumulative incidence of uncomplicated malaria in a cohort of children aged five years and younger, over the 18-week study. We judged the study to be at high risk of bias, as the analysis did not account for clustering or correlation between participants in the same village. The study did not demonstrate an effect of Ivermectin on the cumulative incidence of uncomplicated malaria in the cohort of children over the 18-week study (risk ratio 0.86, 95% confidence interval (CI) 0.62 to 1.17; P = 0.2607; very low-certainty evidence). AUTHORS' CONCLUSIONS: We are uncertain whether community administration of ivermectin has an effect on malaria transmission, based on one trial published to date.

Interplay between Abscisic Acid and Gibberellins, as Related to Ethylene and Sugars, in Regulating Maturation of Non-Climacteric Fruit.

In this review, we address the interaction between abscisic acid (ABA) and gibberellins (GAs) in regulating non-climacteric fruit development and maturation at the molecular level. We review the interplay of both plant growth regulators in regulating these processes in several fruit of economic importance such as grape berries, strawberry, and citrus, and show how understanding this interaction has resulted in useful agronomic management techniques. We then relate the interplay of both hormones with ethylene and other endogenous factors, such as sugar signaling. We finally review the growing knowledge related to abscisic acid, gibberellins, and the genus Citrus. We illustrate why this woody genus can be considered as an emerging model plant for understanding hormonal circuits in regulating different processes, as most of the finest work on this matter in recent years has been performed by using different Citrus species.

Blood markers of oxidative stress are strongly associated with poorer prognosis in colorectal cancer patients.

Oxidative stress has been implicated in the initiation of several cancers, including colorectal cancer (CRC). Whether it also plays a role in CRC prognosis is unclear. We assessed the associations of two oxidative stress biomarkers (Diacron's reactive oxygen metabolites [d-ROMs] and total thiol level [TTL]) with CRC prognosis. CRC patients who were diagnosed in 2003 to 2012 and recruited into a population-based study in Germany (n = 3361) were followed for up to 6 years. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations of d-ROMs and TTL (measured from blood samples collected shortly after CRC diagnosis) with overall survival (OS) and disease-specific survival (DSS) were estimated using multivariable Cox regression. Particularly pronounced associations of higher d-ROMs with lower survival were observed in stage IV patients, with patients in the highest (vs lowest) tertile having much lower OS (HR = 1.52, 95% CI = 1.14-2.04) and DSS (HR = 1.61, 95% CI = 1.20-2.17). For TTL, strong inverse associations of TTL with mortality were observed within all stages. In patients of all stages, those in the highest (vs lowest) quintile had substantially higher OS (HR = 0.48, 95% CI = 0.38-0.62) and DSS (HR = 0.52, 95% CI = 0.39-0.69). The addition of these biomarkers to models that included age, sex, tumor stage and subsite significantly improved the prediction of CRC prognosis. The observed strong associations of higher d-ROMs and lower TTL levels with poorer prognosis even in stage IV patients suggest that oxidative stress contributes significantly to premature mortality in CRC patients and demonstrate a large potential of these biomarkers in enhancing the prediction of CRC prognosis beyond tumor stage.

Magnitude of the Age-Advancement Effect of Comorbidities in Colorectal Cancer Prognosis.

BACKGROUND: Comorbidities and old age independently compromise prognosis of patients with colorectal cancer (CRC). The impact of comorbidities could thus be considered as conveying worse prognosis already at younger ages, but evidence is lacking on how much worsening of prognosis with age is advanced to younger ages in comorbid versus noncomorbid patients. We aimed to quantify, for the first time, the impact of comorbidities on CRC prognosis in "age advancement" of worse prognosis. METHODS: A total of 4,602 patients aged ≥30 years who were diagnosed with CRC in 2003 through 2014 were recruited into a population-based study in the Rhine-Neckar region of Germany and observed over a median period of 5.1 years. Overall comorbidity was quantified using the Charlson comorbidity index (CCI). Hazard ratios and age advancement periods (AAPs) for comorbidities were calculated from multivariable Cox proportional hazards models for relevant survival outcomes. RESULTS: Hazard ratios for CCI scores 1, 2, and ≥3 compared with CCI 0 were 1.25, 1.53, and 2.30 (P<.001) for overall survival and 1.20, 1.48, and 2.03 (P<.001) for disease-free survival, respectively. Corresponding AAP estimates for CCI scores 1, 2, and ≥3 were 5.0 (95% CI, 1.9-8.1), 9.7 (95% CI, 6.1-13.3), and 18.9 years (95% CI, 14.4-23.3) for overall survival and 5.5 (95% CI, 1.5-9.5), 11.7 (95% CI, 7.0-16.4), and 21.0 years (95% CI, 15.1-26.9) for disease-free survival. Particularly pronounced effects of comorbidity on CRC prognosis were observed in patients with stage I-III CRC. CONCLUSIONS: Comorbidities advance the commonly observed deterioration of prognosis with age by many years, meaning that at substantially younger ages, comorbid patients with CRC experience survival rates comparable to those of older patients without comorbidity. This first derivation of AAPs may enhance the empirical basis for treatment decisions in patients with comorbidities and highlight the need to incorporate comorbidities into prognostic nomograms for CRC.

Decreasing Use of Chemotherapy in Older Patients With Stage III Colon Cancer Irrespective of Comorbidities.

BACKGROUND: Chemotherapy underuse in elderly patients (aged ≥75 years) with colon cancer has been reported in previous studies. However, these studies were mostly registry-based and limited in their potential to consider underlying reasons of such undertreatment. This study aimed to evaluate patient and hospital determinants of chemotherapeutic treatment in patients with stage III colon cancer, with a particular focus on age and underlying reasons for nontreatment of elderly patients. METHODS: A total of 629 patients with stage III colon cancer who were diagnosed in 2003 through 2012 and recruited into a population-based study in the Rhine-Neckar region of Germany were included. Information on sociodemographic and lifestyle factors, comorbidities, and treatment was collected from patient interviews and physicians. Patient (with an emphasis on age) and hospital factors were evaluated for their associations with administration of adjuvant chemotherapy overall and of oxaliplatin specifically using multivariable logistic regression. RESULTS: Administration of chemotherapy decreased from 94% in patients aged 30 to 64 years to 51% in those aged ≥75 years. A very strong decline in chemotherapy use with age persisted even after comprehensive adjustment for multiple patient factors-including comorbidities-and hospital factors and was also seen among patients without any major comorbidities. Between 2005 and 2008, and 2009 and 2012, chemotherapy administration in patients aged ≥75 years decreased from 60% to 41%. Among chemotherapy recipients, old age was also strongly associated with higher odds of nonadministration of oxaliplatin. The 2 most commonly reported reasons for chemotherapy nonreceipt among the study population were patient refusal (30%) and old age (24%). CONCLUSIONS: Age was the strongest predictor of chemotherapy underuse, irrespective of comorbidities and even in patients without comorbidities. Such underuse due just to older age in otherwise healthy patients deserves increased attention in clinical practice to ensure that elderly patients also get the best possible care. Patients' refusal as the most frequent reason for chemotherapy nonreceipt also warrants further investigation to exclude misinformation as underlying cause.

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.

How Can Onchocerciasis Elimination in Africa Be Accelerated? Modeling the Impact of Increased Ivermectin Treatment Frequency and Complementary Vector Control.

Background: Great strides have been made toward onchocerciasis elimination by mass drug administration (MDA) of ivermectin. Focusing on MDA-eligible areas, we investigated where the elimination goal can be achieved by 2025 by continuation of current practice (annual MDA with ivermectin) and where intensification or additional vector control is required. We did not consider areas hypoendemic for onchocerciasis with loiasis coendemicity where MDA is contraindicated. Methods: We used 2 previously published mathematical models, ONCHOSIM and EPIONCHO, to simulate future trends in microfilarial prevalence for 80 different settings (defined by precontrol endemicity and past MDA frequency and coverage) under different future treatment scenarios (annual, biannual, or quarterly MDA with different treatment coverage through 2025, with or without vector control strategies), assessing for each strategy whether it eventually leads to elimination. Results: Areas with 40%-50% precontrol microfilarial prevalence and ≥10 years of annual MDA may achieve elimination with a further 7 years of annual MDA, if not achieved already, according to both models. For most areas with 70%-80% precontrol prevalence, ONCHOSIM predicts that either annual or biannual MDA is sufficient to achieve elimination by 2025, whereas EPIONCHO predicts that elimination will not be achieved even with complementary vector control. Conclusions: Whether elimination will be reached by 2025 depends on precontrol endemicity, control history, and strategies chosen from now until 2025. Biannual or quarterly MDA will accelerate progress toward elimination but cannot guarantee it by 2025 in high-endemicity areas. Long-term concomitant MDA and vector control for high-endemicity areas might be useful.

Risk Scores for Predicting Advanced Colorectal Neoplasia in the Average-risk Population: A Systematic Review and Meta-analysis.

OBJECTIVES: A systematic review and meta-analysis was performed to summarize the available evidence on risk scores for predicting advanced colorectal neoplasia (advanced adenomas and cancer) in average-risk and asymptomatic populations undergoing screening colonoscopy. METHODS: PubMed, EMBASE, and Web of Science databases were searched up to 28 March 2018. Studies that developed or validated a risk score to predict the risk of advanced colorectal neoplasia were included. Two reviewers independently extracted study characteristics including diagnostic performance indicators and assessed risk of bias and applicability in the included studies. Meta-analyses were conducted to determine the overall discrimination of risk scores evaluated by more than 1 study. RESULTS: A total of 22 studies including 17 original risk scores were identified. Risk scores included a median number of 5 risk factors. Factors most commonly included were age, sex, family history in first-degree relatives, body mass index and smoking. The area under the receiver operating characteristic curve of risk scores ranged from 0.62 to 0.77 in the individual studies and from 0.61 to 0.70 in the meta-analyses. CONCLUSIONS: Although the majority of available risk scores had relatively weak discriminatory power, they may be of some use for risk stratification in CRC screening. Rather than developing more risk scores based on environmental risk factors, future research should focus on exploring possibilities of enhancing predictive power by combining risk factor data with novel laboratory matters, such as polygenetic risk scores.

In vitro antiprotozoan activity and mechanisms of action of selected Ghanaian medicinal plants against Trypanosoma, Leishmania, and Plasmodium parasites.

Trypanosomiasis, leishmaniasis, and malaria are protozoan infections of public health importance with thousands of new cases recorded annually. Control of these infection(s) with existing chemotherapy is limited by drug toxicity, lengthy parenteral treatment, affordability, and/or the emergence of resistant strains. Medicinal plants on the other hand are used in the treatment of various infectious diseases although their chemical properties are not fully evaluated. In this study, we screened 112 crude extracts from 72 selected Ghanaian medicinal plants for anti-Trypanosoma, anti-Leishmania, and anti-Plasmodium activities in vitro and investigated their mechanisms of action. Twenty-three extracts from 20 plants showed significant antiprotozoan activity against at least 1 of 3 protozoan parasites screened with IC50 values less than 20 µg/ml. Eleven extracts showed high anti-Trypanosoma activity with Bidens pilosa whole plant and Morinda lucida leaf extracts recording the highest activities. Their IC50 (selectivity index [SI]) values were 5.51 µg/ml (35.00) and 5.96 µg/ml (13.09), respectively. Nine extracts had high anti-Leishmania activity with Annona senegalensis and Cassia alata leaf extracts as the most active. Their IC50 (SI) values were 10.8 µg/ml (1.50) and 10.1 µg/ml (0.37), respectively. Six extracts had high anti-Plasmodium activity with the leaf and stem-bark extracts of Terminalia ivorensis recording the highest activity. Their IC50 (SI) values were 7.26 µg/ml (129.36) and 17.45 µg/ml (17.17), respectively. Only M. lucida at 25 µg/ml induced significant apoptosis-like cell death in Trypanosoma parasites. Anti-Leishmania active extracts induced varying morphological changes in Leishmania parasites such as multiple nuclei and/or kinetoplast, incomplete flagella division, or nuclear fragmentation. Active extracts may be potential sources for developing new chemotherapy against these infections.

Twelve-month longitudinal parasitological assessment of lymphatic filariasis-positive individuals: impact of a biannual treatment with ivermectin and albendazole.

OBJECTIVE: Mass drug administration (MDA) for the control of lymphatic filariasis (LF), in Ghana, started in the year 2000. While this had great success in many implementation units, there remain areas with persistent transmission, after more than 10 years of treatment. A closer examination of the parasite populations could help understand the reasons for persistent infections and formulate appropriate strategies to control LF in these areas of persistent transmission. MATERIALS AND METHODS: In a longitudinal study, we assessed the prevalence of microfilaraemia (mf) in two communities with 12 years of MDA in Ghana. In baseline surveys 6 months after the National MDA in 2014, 370 consenting individuals were tested for antigenaemia using immunochromatographic test (ICT) cards and had their mf count determined through night blood surveys. 48 ICT positives, of whom, 17 were positive for mf, were treated with 400 µg/kg ivermectin + 400 mg albendazole and subsequently followed for parasitological assessment at 3-month intervals for 1 year. This overlapped with the National MDA in 2015. RESULTS: There was a 68% parasite clearance 3 months after treatment. The pre-treatment mf count differed significantly from the post-treatment mf counts at 3 months (P = 0.0023), 6 months (P = 0.0051), 9 months (P = 0.0113) and 12 months (P = 0.0008). CONCLUSION: In these settings with persistent LF transmission, twice-yearly treatment may help accelerate LF elimination. Further large-scale evaluations are required to ascertain these findings.

Evaluation of piperonyl butoxide in enhancing the efficacy of pyrethroid insecticides against resistant Anopheles gambiae s.l. in Ghana.

BACKGROUND: Malaria vector control methods involving the use of pyrethroids remain the strategies being used against malaria vectors in Ghana. These methods include the use of long-lasting insecticidal nets and indoor residual spraying in many areas in Ghana. However, there is evidence that pyrethroid resistance is widespread in many areas in Ghana. Synergists have been shown to be useful in inhibiting the enzymes that are responsible for the development of resistance and hence enhance the insecticide susceptibility of Anopheles gambiae sensu lato (s.l.) in many areas. The present study investigated the effect of piperonyl butoxide (PBO) on the susceptibility status of An. gambiae s.l. across some sentinel sites in Ghana. METHODS: Three to five day old An. gambiae s.l. reared from larvae were used in WHO susceptibility tube assays. Batches of 20-25 female adult An. gambiae s.l. were exposed simultaneously to the insecticide alone and to the PBO + insecticide. The knock down rate after 60 min and mortality at 24 h were recorded. RESULTS: Deltamethrin and permethrin resistance of An. gambiae s.l. was observed in all the sites in 2015 and 2016. The mortality after 24 h post exposure for deltamethrin ranged from 16.3% in Weija to 82.3% in Kade, whereas that for permethrin ranged from 3.8% in Gomoa Obuasi to 91.3% in Prestea. A significant increase in susceptibility to deltamethrin and less to permethrin was observed during both 2015 and 2016 years in most of the sites when An. gambiae s.l. mosquitoes were pre-exposed to PBO. CONCLUSION: Findings from this study showed that the use of PBO significantly enhanced the susceptibility of An. gambiae s.l. mosquitoes in most of the sentinel sites. It is recommended that vector control strategies incorporating PBO as a synergist can be effective in killing mosquitoes in the presence of deltamethrin and permethrin resistance.