A molecular and epidemiological study of Vibrio cholerae isolates from cholera outbreaks in southern Ghana

Cholera remains a major global public health threat and continuous emergence of new Vibrio cholerae strains is of major concern. We conducted a molecular epidemiological study to detect virulence markers and antimicrobial resistance patterns of V. cholerae isolates obtained from the 2012-2015 cholera outbreaks in Ghana. Archived clinical isolates obtained from the 2012, 2014 and 2015 cholera outbreaks in Ghana were revived by culture and subjected to microscopy, biochemical identification, serotyping, antibiotic susceptibility testing, molecular detection of distinct virulence factors and Multi-Locus Variable-Number of Tandem-Repeat Analysis (MLVA). Of 277 isolates analysed, 168 (60.6%) were confirmed to be V. cholerae and 109 (39.4%) isolates constituted other bacteria (Escherichia coli, Aeromonas sobria, Pseudomonas aeruginosa, Enterobacter cloacae and Enterococci faecalis). Serotyping the V. cholerae isolates identified 151 (89.9%) as Ogawa, 3 (1.8%) as Inaba and 14 (8.3%) as non-O1/O139 serogroup. The O1 serogroup isolates (154/168, 91.7%) carried the cholera toxin ctxB gene as detected by PCR. Additional virulence genes detected include zot, tcpA, ace, rtxC, toxR, rtxA, tcpP, hlyA and tagA. The most common and rare virulence factors detected among the isolates were rtxC (165 isolates) and tcpP (50 isolates) respectively. All isolates from 2014 and 2015 were multidrug resistant against the selected antibiotics. MLVA differentiated the isolates into 2 large unique clones A and B, with each predominating in a particular year. Spatial analysis showed clustering of most isolates at Ablekuma sub-district. Identification of several virulence genes among the two different genotypes of V. cholerae isolates and resistance to first- and second-line antibiotics, calls for scaleup of preventive strategies to reduce transmission, and strengthening of public health laboratories for rapid antimicrobial susceptibility testing to guide accurate treatment. Our findings support the current WHO licensed cholera vaccines which include both O1 Inaba and Ogawa serotypes

Self-reported use of anti-malarial drugs and health facility management of malaria in Ghana

<p>Abstract</p> <p>Objective</p> <p>To assess the appropriateness of self-reported use of anti-malarial drugs prior to health facility attendance, and the management of malaria in two health facilities in Ghana.</p> <p>Method</p> <p>A structured questionnaire was used to collect data from 500 respondents who were diagnosed clinically and/or parasitologically for malaria at Agogo Presbyterian Hospital and Suntreso Polyclinic, both in the Ashanti Region of Ghana. Collected information included previous use of anti-malarial drugs prior to attending the health facilities, types of drugs used, how the drugs were used, and the sources of the drugs. In addition, the anti-malarial therapy given and outcomes at the two health facilities were assessed.</p> <p>Results</p> <p>Of the 500 patients interviewed, 17% had severe malaria, 8% had moderate to severe malaria and 75% had uncomplicated malaria. Forty three percent of the respondents had taken anti-malarial drugs within two weeks prior to hospital attendance. The most commonly used anti-malarials were chloroquine (76%), sulphadoxine-pyrimethamine (9%), herbal preparations (9%) and amodiaquine (6%). The sources of these medicines were licensed chemical sellers (50%), pharmacies (21%), neighbouring clinics (9%) or "other" sources (20%) including left-over medicines at home. One hundred and sixty three (77%) of the 213 patients who had used anti-malarial drugs prior to attending the health facilities, used the drugs inappropriately. At the health facilities, the anti-malarials were prescribed and used according to the national standard treatment guidelines with good outcomes.</p> <p>Conclusion</p> <p>Prevalence of inappropriate use of anti-malarials in the community in Ghana is high. There is need for enhanced public health education on home-based management of malaria and training for workers in medicine supply outlets to ensure effective use of anti-malaria drugs in the country.</p

imPlatelet classifier: image-converted RNA biomarker profiles enable blood-based cancer diagnostics

Liquid biopsies offer a minimally invasive sample collection, outperforming traditional biopsies employed for cancer evaluation. The widely used material is blood, which is the source of tumor-educated platelets. Here, we developed the imPlatelet classifier, which converts RNA-sequenced platelet data into images in which each pixel corresponds to the expression level of a certain gene. Biological knowledge from the Kyoto Encyclopedia of Genes and Genomes was also implemented to improve accuracy. Images obtained from samples can then be compared against standard images for specific cancers to determine a diagnosis. We tested imPlatelet on a cohort of 401 non-small cell lung cancer patients, 62 sarcoma patients, and 28 ovarian cancer patients. imPlatelet provided excellent discrimination between lung cancer cases and healthy controls, with accuracy equal to 1 in the independent dataset. When discriminating between noncancer cases and sarcoma or ovarian cancer patients, accuracy equaled 0.91 or 0.95, respectively, in the independent datasets. According to our knowledge, this is the first study implementing an image-based deep-learning approach combined with biological knowledge to classify human samples. The performance of imPlatelet considerably exceeds previously published methods and our own alternative attempts of sample discrimination. We show that the deep-learning image-based classifier accurately identifies cancer, even when a limited number of samples are available.publishedVersio

Inequities in maternal and child health outcomes and interventions in Ghana

<p>Abstract</p> <p>Background</p> <p>With the date for achieving the targets of the Millennium Development Goals (MDGs) approaching fast, there is a heightened concern about equity, as inequities hamper progress towards the MDGs. Equity-focused approaches have the potential to accelerate the progress towards achieving the health-related MDGs faster than the current pace in a more cost-effective and sustainable manner. Ghana's rate of progress towards MDGs 4 and 5 related to reducing child and maternal mortality respectively is less than what is required to achieve the targets. The objective of this paper is to examine the equity dimension of child and maternal health outcomes and interventions using Ghana as a case study.</p> <p>Methods</p> <p>Data from Ghana Demographic and Health Survey 2008 report is analyzed for inequities in selected maternal and child health outcomes and interventions using population-weighted, regression-based measures: slope index of inequality and relative index of inequality.</p> <p>Results</p> <p>No statistically significant inequities are observed in infant and under-five mortality, perinatal mortality, wasting and acute respiratory infection in children. However, stunting, underweight in under-five children, anaemia in children and women, childhood diarrhoea and underweight in women (BMI < 18.5) show inequities that are to the disadvantage of the poorest. The rates significantly decrease among the wealthiest quintile as compared to the poorest. In contrast, overweight (BMI 25-29.9) and obesity (BMI ≥ 30) among women reveals a different trend - there are inequities in favour of the poorest. In other words, in Ghana overweight and obesity increase significantly among women in the wealthiest quintile compared to the poorest. With respect to interventions: treatment of diarrhoea in children, receiving all basic vaccines among children and sleeping under ITN (children and pregnant women) have no wealth-related gradient. Skilled care at birth, deliveries in a health facility (both public and private), caesarean section, use of modern contraceptives and intermittent preventive treatment for malaria during pregnancy all indicate gradients that are in favour of the wealthiest. The poorest use less of these interventions. Not unexpectedly, there is more use of home delivery among women of the poorest quintile.</p> <p>Conclusion</p> <p>Significant Inequities are observed in many of the selected child and maternal health outcomes and interventions. Failure to address these inequities vigorously is likely to lead to non-achievement of the MDG targets related to improving child and maternal health (MDGs 4 and 5). The government should therefore give due attention to tackling inequities in health outcomes and use of interventions by implementing equity-enhancing measure both within and outside the health sector in line with the principles of Primary Health Care and the recommendations of the WHO Commission on Social Determinants of Health.</p

Assessment of severe malaria in a multicenter, phase III, RTS, S/AS01 malaria candidate vaccine trial: case definition, standardization of data collection and patient care

BACKGROUND\ud \ud An effective malaria vaccine, deployed in conjunction with other malaria interventions, is likely to substantially reduce the malaria burden. Efficacy against severe malaria will be a key driver for decisions on implementation. An initial study of an RTS, S vaccine candidate showed promising efficacy against severe malaria in children in Mozambique. Further evidence of its protective efficacy will be gained in a pivotal, multi-centre, phase III study. This paper describes the case definitions of severe malaria used in this study and the programme for standardized assessment of severe malaria according to the case definition.\ud \ud METHODS\ud \ud Case definitions of severe malaria were developed from a literature review and a consensus meeting of expert consultants and the RTS, S Clinical Trial Partnership Committee, in collaboration with the World Health Organization and the Malaria Clinical Trials Alliance. The same groups, with input from an Independent Data Monitoring Committee, developed and implemented a programme for standardized data collection.The case definitions developed reflect the typical presentations of severe malaria in African hospitals. Markers of disease severity were chosen on the basis of their association with poor outcome, occurrence in a significant proportion of cases and on an ability to standardize their measurement across research centres. For the primary case definition, one or more clinical and/or laboratory markers of disease severity have to be present, four major co-morbidities (pneumonia, meningitis, bacteraemia or gastroenteritis with severe dehydration) are excluded, and a Plasmodium falciparum parasite density threshold is introduced, in order to maximize the specificity of the case definition. Secondary case definitions allow inclusion of co-morbidities and/or allow for the presence of parasitaemia at any density. The programmatic implementation of standardized case assessment included a clinical algorithm for evaluating seriously sick children, improvements to care delivery and a robust training and evaluation programme for clinicians.\ud \ud CONCLUSIONS\ud \ud The case definition developed for the pivotal phase III RTS, S vaccine study is consistent with WHO recommendations, is locally applicable and appropriately balances sensitivity and specificity in the diagnosis of severe malaria. Processes set up to standardize severe malaria data collection will allow robust assessment of the efficacy of the RTS, S vaccine against severe malaria, strengthen local capacity and benefit patient care for subjects in the trial.\ud \ud TRIAL REGISTRATION\ud \ud Clinicaltrials.gov NCT00866619

Global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017

Background Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980–2017 and forecast these estimates to 2030 for 195 countries and territories. Methods We determined a modelling strategy for each country on the basis of the availability and quality of data. For countries and territories with data from population-based seroprevalence surveys or antenatal care clinics, we estimated prevalence and incidence using an open-source version of the Estimation and Projection Package—a natural history model originally developed by the UNAIDS Reference Group on Estimates, Modelling, and Projections. For countries with cause-specific vital registration data, we corrected data for garbage coding (ie, deaths coded to an intermediate, immediate, or poorly defined cause) and HIV misclassification. We developed a process of cohort incidence bias adjustment to use information on survival and deaths recorded in vital registration to back-calculate HIV incidence. For countries without any representative data on HIV, we produced incidence estimates by pulling information from observed bias in the geographical region. We used a re-coded version of the Spectrum model (a cohort component model that uses rates of disease progression and HIV mortality on and off ART) to produce age-sex-specific incidence, prevalence, and mortality, and treatment coverage results for all countries, and forecast these measures to 2030 using Spectrum with inputs that were extended on the basis of past trends in treatment scale-up and new infections. Findings Global HIV mortality peaked in 2006 with 1·95 million deaths (95% uncertainty interval 1·87–2·04) and has since decreased to 0·95 million deaths (0·91–1·01) in 2017. New cases of HIV globally peaked in 1999 (3·16 million, 2·79–3·67) and since then have gradually decreased to 1·94 million (1·63–2·29) in 2017. These trends, along with ART scale-up, have globally resulted in increased prevalence, with 36·8 million (34·8–39·2) people living with HIV in 2017. Prevalence of HIV was highest in southern sub-Saharan Africa in 2017, and countries in the region had ART coverage ranging from 65·7% in Lesotho to 85·7% in eSwatini. Our forecasts showed that 54 countries will meet the UNAIDS target of 81% ART coverage by 2020 and 12 countries are on track to meet 90% ART coverage by 2030. Forecasted results estimate that few countries will meet the UNAIDS 2020 and 2030 mortality and incidence targets. Interpretation Despite progress in reducing HIV-related mortality over the past decade, slow decreases in incidence, combined with the current context of stagnated funding for related interventions, mean that many countries are not on track to reach the 2020 and 2030 global targets for reduction in incidence and mortality. With a growing population of people living with HIV, it will continue to be a major threat to public health for years to come. The pace of progress needs to be hastened by continuing to expand access to ART and increasing investments in proven HIV prevention initiatives that can be scaled up to have population-level impact

Perceptions and utilization of the anti-malarials artemether-lumefantrine and dihydroartemisinin-piperaquine in young children in the Chikhwawa District of Malawi: a mixed methods study

Background Adherence to anti-malarial dosing schedules is essential to ensure effective treatment. Measuring adherence is challenging due to recall issues and the participants’ awareness of the desired behaviour influencing their actions or responses. This study used qualitative methods, which allow for rapport building, to explore issues around anti-malarial utilization in young children, and used the results to guide the development of a context specific questionnaire on perceptions and adherence to artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ). Methods Qualitative data collection included 12 focus group discussions which explored community perceptions of anti-malarials and experiences of administering medications to children. Critical incidence interviews were conducted with 22 caregivers to explore experiences of administering the dispersible or original formulation of AL to young children during recent febrile episodes. A structured questionnaire was used to gather data on experience of recent treatment and adherence to anti-malarials during follow-up visits with 218 caregivers whose child was recently treated with either dispersible AL or DHA-PPQ. Discussion/Conclusion Caregivers experience great difficulty in administering medication to children. While the sweet taste of dispersible AL may have reduced conflict between the child and caregiver, sub-optimal dosing due to medication loss remained a problem and overall adherence was greater among those receiving DHA-PPQ, which requires fewer doses. Some caregivers were found to deliberately alter the dosing schedule according to whether they perceived the medication to be too weak or strong. They also developed theories for poor treatment outcomes, such as attributing this to lack of compatibility between the medication and the child. Health education messages should be strengthened to ensure a combination of clear pictorial and verbal instructions are used during dispensing, and consequences of under and over-dosing are explained alongside appropriate responses to possible adverse events. Further optimizing of anti-malarial adherence among children requires the development of anti-malarials with pharmacological properties that allow user-friendly administration and simplified dosing schedules