Potential Impact of Intermittent Preventive Treatment (IPT) on Spread of Drug-Resistant Malaria

BACKGROUND: Treatment of asymptomatic individuals, regardless of their malaria infection status, with regularly spaced therapeutic doses of antimalarial drugs has been proposed as a method for reducing malaria morbidity and mortality. This strategy, called intermittent preventive treatment (IPT), is currently employed for pregnant women and is being studied for infants (IPTi) as well. As with any drug-based intervention strategy, it is important to understand how implementation may affect the spread of drug-resistant parasites. This is a difficult issue to address experimentally because of the limited size and duration of IPTi trials as well as the intractability of distinguishing the spread of resistance due to conventional treatment of malaria episodes versus that due to IPTi when the same drug is used in both contexts. METHODS AND FINDINGS: Using a mathematical model, we evaluated the possible impact of treating individuals with antimalarial drugs at regular intervals regardless of their infection status. We translated individual treatment strategies and drug pharmacokinetics into parasite population dynamic effects and show that immunity, treatment rate, drug decay kinetics, and presumptive treatment rate are important factors in the spread of drug-resistant parasites. Our model predicts that partially resistant parasites are more likely to spread in low-transmission areas, but fully resistant parasites are more likely to spread under conditions of high transmission, which is consistent with some epidemiological observations. We were also able to distinguish between spread of resistance due to treatment of symptomatic infections and that due to IPTi. We showed that IPTi could accelerate the spread of resistant parasites, but this effect was only likely to be significant in areas of low or unstable transmission. CONCLUSIONS: The results presented here demonstrate the importance of considering both the half-life of a drug and the existing level of resistance when choosing a drug for IPTi. Drugs to which little or no resistance exists are not advisable for IPT in high-transmission areas, but IPTi is not likely to significantly impact the spread of highly resistant parasites in areas where partial resistance is already established. IPTi is more likely to accelerate the spread of resistance in high-transmission areas than is IPT in adults (i.e., pregnant women)

Comparative gene transfer efficiency of low molecular weight polylysine DNA-condensing peptides

In a previous report (M.S. Wadhwa et al . (1997) Bioconjugate Chem. 8, 81–88), we synthesized a panel of polylysine-containing peptides and determined that a minimal repeating lysine chain of 18 residues followed by a tryptophan and an alkylated cysteine residue (AlkCWK 18 ) resulted in the formation of optimal size (78 nm diameter) plasmid DNA condensates that mediated efficient in vitro gene transfer. Shorter polylysine chains produced larger DNA condensates and mediated much lower gene expression while longer lysine chains were equivalent to AlkCWK 18 . Surprisingly, AlkCWK 18 (molecular weight 2672) was a much better gene transfer agent than commercially available low molecular weight polylysine (molecular weight 1000–4000), despite its similar molecular weight. Possible explanations were that the cysteine or tryptophan residue in AlkCWK 18 contributed to the DNA binding and the formation of small condensates or that the homogeneity of AlkCWK 18 relative to low molecular weight polylysine facilitated optimal condensation. To test these hypotheses, the present study prepared AlkCYK 18 and K 20 and used these to form DNA condensates and conduct in vitro gene transfer. The results established that DNA condensates prepared with either AlkCYK 18 or K 20 possessed identical particle size and mediated in vitro gene transfer efficiencies that were indistinguishable from AlkCWK 18 DNA condensates, eliminating the possibility of contributions from cysteine or tryptophan. However, a detailed chromatographic and electrospray mass spectrometry analysis of low molecular weight polylysine revealed it to possess a much lower than anticipated average chain length of dp 6. Thus, the short chain length of low molecular weight polylysine explains its inability to form small DNA condensates and mediate efficient gene transfer relative to AlkCWK 18 DNA condensates. These experiments further emphasize the need to develop homogenous low molecular weight carrier molecules for nonviral gene delivery.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74767/1/j.1399-3011.1999.00104.x.pd

The promise and potential challenges of intermittent preventive treatment for malaria in infants (IPTi)

Intermittent preventive treatment (IPT) administers a full therapeutic course of an anti-malarial drug at predetermined intervals, regardless of infection or disease status. It is recommended by the World Health Organization (WHO) for protecting pregnant women from the adverse effects of malaria (IPTp) and shows great potential as a strategy for reducing illness from malaria during infancy (IPTi). Administered concurrently with standard immunizations, IPTi is expected to reduce the frequency of clinical disease, but to allow blood-stage infections to occur between treatments, thus allowing parasite-specific immunity to develop. While wide deployment of IPTi is being considered, it is important to assess other potential effects. Transmission conditions, drug choice and administration schedule will likely affect the possibility of post-treatment rebound in child morbidity and mortality and the increased spread of parasite drug resistance and should be considered when implementing IPTi

What can secondary data tell us about household food insecurity in a high-income country context?

In the absence of routinely collected household food insecurity data, this study investigated what could be determined about the nature and prevalence of household food insecurity in Scotland from secondary data. Secondary analysis of the Living Costs and Food Survey (2007–2012) was conducted to calculate weekly food expenditure and its ratio to equivalised income for households below average income (HBAI) and above average income (non-HBAI). Diet Quality Index (DQI) scores were calculated for this survey and the Scottish Health Survey (SHeS, 2008 and 2012). Secondary data provided a partial picture of food insecurity prevalence in Scotland, and a limited picture of differences in diet quality. In 2012, HBAI spent significantly less in absolute terms per week on food and non-alcoholic drinks (£53.85) compared to non-HBAI (£86.73), but proportionately more of their income (29% and 15% respectively). Poorer households were less likely to achieve recommended fruit and vegetable intakes than were more affluent households. The mean DQI score (SHeS data) of HBAI fell between 2008 and 2012, and was significantly lower than the mean score for non-HBAI in 2012. Secondary data are insufficient to generate the robust and comprehensive picture needed to monitor the incidence and prevalence of food insecurity in Scotland.</p

Developmental allometry and paediatric malaria

WHO estimates that 80% of mortality due to malaria occurs among infants and young children. Though it has long been established that malaria disproportionately affects children under age five, our understanding of the underlying biological mechanisms for this distribution remains incomplete. Many studies use age as an indicator of exposure, but age may affect malaria burden independently of previous exposure. Not only does the severity of malaria infection change with age, but the clinical manifestation of disease does as well: younger children are more likely to suffer severe anaemia, while older children are more likely to develop cerebral malaria. Intensity of transmission and acquired immunity are important determinants of this age variation, but age differences remain consistent over varying transmission levels. Thus, age differences in clinical presentation may involve inherent age-related factors as well as still-undiscovered facets of acquired immunity, perhaps including the rates at which relevant aspects of immunity are acquired. The concept of "allometry" - the relative growth of a part in relation to that of an entire organism or to a standard - has not previously been applied in the context of malaria infection. However, because malaria affects a number of organs and cells, including the liver, red blood cells, white blood cells, and spleen, which may intrinsically develop at rates partly independent of each other and of a child's overall size, developmental allometry may influence the course and consequences of malaria infection. Here, scattered items of evidence have been collected from a variety of disciplines, aiming to suggest possible research paths for investigating exposure-independent age differences affecting clinical outcomes of malaria infection

Access to forensic science. [Case study]

This case study discusses an after-school programme for secondary-school pupils from "low attainment/progression" schools, which aimed to facilitate wider access to university - particularly in STEM subjects. The course focused specifically on toxicology, with classes based in RGU's chemistry-, microbiology-, molecular biology- and computing laboratories

Grass-Eating Behaviour in the Domestic Dog, "Canis familiaris"

There is a paucity of information on grass eating in the domestic dog, "Canis familiaris". Various explanations have been proposed for grass-eating behaviour including grass as an emetic, laxative, or as self-medication of gastrointestinal distress. In addition, grass-related commercial products are marketed as digestive aids for dogs. However, there is no known explanation for grass-eating behaviour as there have been no controlled experiments that investigate it. Several aspects and theories of grass eating were explored in a series of five studies for the current thesis. Grass-eating behaviour was common among dogs observed in their home environment and dogs observed throughout the controlled studies: 95 of the 99 dogs that were observed ate grass. There were 2,769 observed grass-eating events during 1,444 minutes (24.1 hours) of time spent eating grass. It was found that grass eating is an innate behaviour that can be influenced in 5- to 7-week-old puppies by their mother’s grass eating habits. Two self-medication theories were investigated and dogs in the current project did not eat grass to self-medicate a naturally harboured nematode burden or to moderate a mild gastrointestinal disturbance. The high frequency of grass eating compared with the very low incidence of vomiting also did not support the theory that dogs eat grass as an emetic. However, the prevalence of grass-eating behaviour in wolves, puppies, and adult dogs suggests a possible biological purpose. Grass may be seen as a food source as dogs were less likely to eat grass when satiated. Similarly, dogs spent more time eating grass the longer it had been since their daily meal. Further research could investigate the chemical composition of grass and the putative laxative effects of grass or its various components

Empowering International Students to Succeed : an Innovative and Beneficial Initiative for Health Professions

International students report higher sociocultural and academic stress when settling into a new university compared with their local counterparts. Three disciplines in the health professions collaborated to create a transition program addressing international student health and well-being in Australia. Commencing students and senior student mentors participated in a four-session program of activities to reflect on their current study/work practices and learn self-management strategies. They developed plans for coping with cultural, language, academic, and social barriers, and assisted in improving physical and mental health and well-being. Of the 26 participants who attended sessions, 15 participated in in-depth interviews. Facilitating adjustment, establishing relationships, gaining new skills and knowledge, and transforming beliefs and behavior were the four themes identified that captured and explicated the impact of the initiative. Although limited by the number of student participants, the program demonstrated a positive impact in creating a supportive learning environment for international students.</p