Deepika Fernando

Genome-wide and fine-resolution association analysis of malaria in West Africa.

We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 × 10−7 to P = 4 × 10−14, with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.

Primaquine in vivax malaria: an update and review on management issues

Primaquine was officially licensed as an anti-malarial drug by the FDA in 1952. It has remained the only FDA licensed drug capable of clearing the intra-hepatic schizonts and hypnozoites of Plasmodium vivax. This update and review focuses on five major aspects of primaquine use in treatment of vivax malaria, namely: a) evidence of efficacy of primaquine for its current indications; b) potential hazards of its widespread use, c) critical analysis of reported resistance against primaquine containing regimens; d) evidence for combining primaquine with artemisinins in areas of chloroquine resistance; and e) the potential for replacement of primaquine with newer drugs.

Malaria in school-age children in Africa: an increasingly important challenge.

School‐age children have attracted relatively little attention as a group in need of special measures to protect them against malaria. However, increasing success in lowering the level of malaria transmission in many previously highly endemic areas will result in children acquiring immunity to malaria later in life than has been the case in the past. Thus, it can be anticipated that in the coming years there will be an increase in the incidence of both uncomplicated and severe malaria in school‐age children in many previously highly endemic areas. In this review, which focuses primarily on Africa, recent data on the prevalence of malaria parasitaemia and on the incidence of clinical malaria in African school‐age children are presented and evidence that malaria adversely effects school performance is reviewed. Long‐lasting insecticide treated bednets (LLIN) are an effective method of malaria control but several studies have shown that school‐age children use LLINs less frequently than other population groups. Antimalarial drugs are being used in different ways to control malaria in school‐age children including screening and treatment and intermittent preventive treatment. Some studies of chemoprevention in school‐age children have shown reductions in anaemia and improved school performance but this has not been the case in all trials and more research is needed to identify the situations in which chemoprevention is likely to be most effective and, in these situations, which type of intervention should be used. In the longer term, malaria vaccines may have an important role in protecting this important section of the community from malaria. Regardless of the control approach selected, it is important this is incorporated into the overall programme of measures being undertaken to enhance the health of African school‐age children.

Scrub typhus: pathophysiology, clinical manifestations and prognosis

Scrub typhus is a zoonosis caused by the pathogen Orientia tsutsugamushi (O. tsutsugamushi). The disease has significant prevalence in eastern and Southeast Asia. Usually presenting as an acute febrile illness, the diagnosis is often missed because of similarities with other tropical febrile infections. Many unusual manifestations are present, and these are described in this review, together with an outline of current knowledge of pathophysiology. Awareness of these unusual clinical manifestations will help the clinician to arrive at an early diagnosis, resulting in early administration of appropriate antibiotics. Prognostic indicators for severe disease have not yet been clearly established.

Short-term impact of an acute attack of malaria on the cognitive performance of schoolchildren living in a malaria-endemic area of Sri Lanka

A prospective study was conducted from January 1998 to November 1999 in a malaria-endemic area of Sri Lanka to determine the short-term impact of an acute attack of malaria on the cognitive performance of 648 schoolchildren attending grades 1 to 5 (mostly aged 6-11 years) in 4 schools. Three groups were studied comprising children with malaria, children with non-malarial fever, and healthy controls. Cognitive performance in language and mathematics at the time of presentation and 2 weeks later was assessed. At the time of presentation, children with malaria scored significantly less in both mathematics and language than children with non-malarial fever and healthy controls. Two weeks later, the mathematics and language scores of children with malaria improved but the scores were significantly lower than the scores of children with non-malarial fever (P < 0.001) and controls (P < 0.001). Having malaria was a significant predictor of cognitive performance after controlling for other confounding factors. These findings suggest that an acute attack of uncomplicated malaria causes significant short-term impairment of cognitive performance. The impairment persists for more than 2 weeks and appears to be cumulative with repeated attacks of malaria.

Pharmacological management of tetanus: an evidence-based review

Tetanus is becoming rarer in both industrialized and developing nations due to an effective vaccination program. In 2010, the World Health Organization estimated there was a 93% reduction in newborns dying from tetanus worldwide, compared to the situation in the late 1980s. Due to its rarity, many diagnostic delays occur as physicians may not consider the diagnosis until the manifestations become overt. Without timely diagnosis and proper treatment, severe tetanus is fatal (mortality is also influenced by the comorbidities of the patient). The principles of treating tetanus are: reducing muscle spasms, rigidity and autonomic instability (with ventilatory support when necessary); neutralization of tetanus toxin with human antitetanus immunoglobulin or equine antitetanus sera; wound debridement; and administration of antibiotics to eradicate locally proliferating bacteria at the wound site. It is difficult to conduct trials on different treatment modalities in tetanus due to both logistical and ethical reasons. However, it is imperative that physicians are aware of the best evidence-based treatment strategies currently available to improve the outcome of patients. This review concentrates on analyzing the current evidence on the pharmacological management of tetanus.

Characterization of imported malaria, the largest threat to sustained malaria elimination from Sri Lanka

Sri Lanka has reached zero indigenous malaria cases in November 2012, two years before its targeted deadline for elimination. Currently, the biggest threat to the elimination efforts are the risk of resurgence of malaria due to imported cases. This paper describes two clusters of imported malaria infections reported in 2013 and 2014, one among a group of Pakistani asylum-seekers resident in Sri Lanka, and the other amongst local fishermen who returned from Sierra Leone. The two clusters studied reveal the potential impact of imported malaria on the risk of reintroducing the disease, as importation is the only source of malaria in the country at present. In the event of a case occurring, detection is a major challenge both amongst individuals returning from malaria endemic countries and the local population, as malaria is fast becoming a “forgotten” disease amongst health care providers. In spite of a very good coverage of diagnostic services (microscopy and rapid diagnostic tests) throughout the country, malaria is being repeatedly overlooked by health care providers even when individuals present with fever and a recent history of travel to a malaria endemic country. Given the high receptivity to malaria in previously endemic areas of the country due to the prevalence of the vector mosquito, such cases pose a significant threat for the reintroduction of malaria to Sri Lanka. The challenges faced by the Anti Malaria Campaign and measures taken to prevent the resurgence of malaria are discussed here.

Toxocara seropositivity in Sri Lankan children with asthma

Background:  Toxocariasis occurs in humans due to infection with Toxocara canis or T. cati, the nematode parasites of dogs and cats, respectively. The relationship between toxocariasis and asthma is complex, with some studies demonstrating that children with asthma were more likely to be Toxocara seropositive as compared to non‐asthmatic children, and other studies indicating no such significant relationship. The aim of the present study was to investigate Toxocara seropositivity and its association with asthma in a selected group of Sri Lankan children.

Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

AbstractBackgroundMany studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels.MethodsSera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP)4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels.ResultsMalaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)4 epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2.ConclusionAlthough the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of combining data from sites with heterogeneous malaria transmission levels across Africa and Asia with which to explore genetic effects on anti-malarial immunity.

e-Learning in medical education: Guide supplement 32.6--Practical application.

The use of computing and the internet in education is known as Electronic Learning or, more typically, e-learning, and is fast becoming an important component of healthcare education (Ellaway & Masters 2008). E-learning has several advantages over the traditional methods of medical instruction and assessment; e-learning makes learning more interactive, offers immediate and student-specific feedback, allows for individually tailored instruction, enables objective testing and makes learning more entertaining. e-Learning is best delivered through a Virtual Learning Environment (VLE). A VLE is a computer-based software system designed to support teaching and learning in an educational setting, i.e. school and university (Popat et al. 2007; Weller 2007). A VLE provides a wide collection of tools such as those for interactive learning, assessment, communication, uploading of content, return of students’ work, peer assessment, administration of student groups, collecting and organizing student grades, questionnaires, tracking tools, etc. Originally created for distance education, VLEs are now used most often to supplement face-to-face teaching. VLEs allow instructors/teachers and learners/students to interact in an online community, without being present in the same physical location or time frame. The core of a VLE is a Learning Management System (LMS), which is a collective term used to describe a set of well configured, regularly monitored and centrally managed software tools designed to handle user learning interventions. The Faculty of Medicine, University of Colombo is the oldest and largest medical faculty school in Sri Lanka. Ten years ago the Faculty switched over from a traditional teacher/disciplinebased curriculum to an integrated module-based curriculum.