[Show abstract][Hide abstract] ABSTRACT: Background: The World Allergy Organization estimates that 40 % of the world's population is affected by allergic dis‑ eases. The International Study of Asthma and Allergies in Childhood has completed Phase III and it has now become clear that these diseases have increased in developing countries, especially Africa, where prevalence rates were for‑ merly low. Despite an increase in studies in Africa, few sub‑Saharan West African countries are represented; the focus has remained on urban populations and little attention has been paid to rural sub‑Saharan Africa. Methods: We performed an allergy survey in a birth cohort of children aged less than 15 years in rural Senegal and implemented an ISAAC questionnaire. We carried out a complete blood count and serological analyses for IgE levels against common allergens and mosquito saliva. Results: The prevalence rates of asthma, rhinoconjunctivitis (RC) and atopic dermatitis (AD) were 12.8, 12.5 and 12.2 % respectively. Specific IgE (sIgE) levels against mosquito spp. salivary gland antigens were significantly associ‑ ated with AD; sIgE levels against selected true grasses (Poaceae) were significantly associated with RC. sIgE levels against house dust mite spp. were not associated with asthma, but were significantly correlated with mosquito IgE levels. Such cross‑reactivity may blur the association between HDM sIgE and asthma. Consumption of seafood, storing whey cream, using plant fibre bedding and presence of carpet were significantly associated with increased risk of RC. The association of seafood may be the result of histamine intoxication from molluscs prepared by putrefaction. Cat presence and dog contact were associated with increased risk of asthma. Cow contact was associated with increased risk of AD. Conclusions: Our allergy study in rural West Africa revealed lower prevalence rates than the majority of African urban settings. Although several associated known risk factors were identified, there were associations specific to the region. The identification of probable artefactual dietary phenomena is a challenge for robust diagnosis of allergic disease. The association AD with mosquito saliva, a common allergen in rural settings, warrants specific attention. Further studies in rural Africa are needed to address the aetiology of allergy in a non‑urban environment.
Allergy Asthma and Clinical Immunology 08/2015; 11:24. DOI:10.1186/s13223-015-0090-0
[Show abstract][Hide abstract] ABSTRACT: Background: Over 2.5 billion people are exposed to the risk of contracting dengue fever (DF). Early diagnosis of DF helps to diminish its burden on public health. Real-time reverse transcription polymerase amplification assays (RT-PCR) are the standard method for molecular detection of the dengue virus (DENV). Real-time RT-PCR analysis is not suitable for on-site screening since mobile devices are large, expensive, and complex. In this study, two RT-recombinase polymerase amplification (RT-RPA) assays were developed to detect DENV1-4.
Using two quantitative RNA molecular standards, the analytical sensitivity of a RT-RPA targeting the 3´non-translated region of DENV1-4 was found to range from 14 (DENV4) to 241 (DENV1-3) RNA molecules detected. The assay was specific and did not cross detect other Flaviviruses. The RT-RPA assay was tested in a mobile laboratory combining magnetic-bead based total nucleic acid extraction and a portable detection device in Kedougou (Senegal) and in Bangkok (Thailand). In Kedougou, the RT-RPA was operated at an ambient temperature of 38°C with auxiliary electricity tapped from a motor vehicle and yielded a clinical sensitivity and specificity of 98% (n=31) and 100% (n=23), respectively. While in the field trial in Bangkok, the clinical sensitivity and specificity were 72% (n=90) and 100%(n=41), respectively.
During the first 5 days of infection, the developed DENV1-4 RT-RPA assays constitute a suitable accurate and rapid assay for DENV diagnosis. Moreover, the use of a portable fluorescence-reading device broadens its application potential to the point-of-care for outbreak investigations.
PLoS ONE 06/2015; 10(6):e0129682. DOI:10.1371/journal.pone.0129682. · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Malaria transmission intensity is highly heterogeneous even at a very small scale. Implementing targeted intervention in malaria transmission hotspots offers the potential to reduce the burden of disease both locally and in adjacent areas. Transmission of malaria parasites from man to mosquito requires the production of gametocyte stage parasites. Cluster analysis of a 19-year long cohort study for gametocyte carriage revealed spatially defined game-tocyte hotspots that occurred during the time when chloroquine was the drug used for clinical case treatment. In addition to known risk factors for gametocyte carriage, notably young age (<15 years old) and associated with a clinical episode, blood groups B and O increased risk compared to groups A and AB. A hotspot of clinical P. falciparum clinical episodes that overlapped the gametocyte hotspots was also identified. Gametocyte positivity was found to be increased in individuals who had been treated with chloroquine, as opposed to other drug treatment regimens, for a clinical P. falciparum episode up to 30 days previously. It seems likely the hotspots were generated by a vicious circle of ineffective treatment of clinical cases and concomitant gametocyte production in a sub-population characterized by an increased prevalence of all the identified risk factors. While rapid access to treatment with an effective anti-malarial can reduce the duration of gametocyte carriage and onward parasite transmission, localised hotspots represent a challenge to malaria control and eventual eradication.
PLoS ONE 04/2015; 10(4):e0123102. DOI:10.1371/journal.pone.0123102 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Malaria remains a major worldwide public health problem with ~207 million cases and ~627,000 deaths per year, mainly affecting children under five years of age in Africa. Recent efforts at elaborating a genetic architecture of malaria have focused on severe malaria, leading to the identification of two new genes and confirmation of previously known variants in HBB, ABO and G6PD, by exploring the whole human genome in genome-wide association (GWA) studies. Molecular pathways controlling phenotypes representing effectiveness of host immunity, notably parasitemia and IgG levels, are of particular interest given the current lack of an efficacious vaccine and the need for new treatment options.
We propose a global causal framework of malaria phenotypes implicating progression from the initial infection with Plasmodium spp. to the development of the infection through liver and blood-stage multiplication cycles (parasitemia as a quantitative trait), to clinical malaria attack, and finally to severe malaria. Genetic polymorphism may control any of these stages, such that preceding stages act as mediators of subsequent stages. A biomarker of humoral immunity, IgG levels, can also be integrated into the framework, potentially mediating the impact of polymorphism by limiting parasitemia levels. Current knowledge of the genetic basis of parasitemia levels and IgG levels is reviewed through key examples including the hemoglobinopathies, showing that the protective effect of HBB variants on malaria clinical phenotypes may partially be mediated through parasitemia and cytophilic IgG levels. Another example is the IgG receptor FcγRIIa, encoded by FCGR2A, such that H131 homozygotes displayed higher IgG2 levels and were protective against high parasitemia and onset of malaria symptoms as shown in a causal diagram.
We thus underline the value of parasitemia and IgG levels as phenotypes in the understanding of the human genetic architecture of malaria, and the need for applying GWA approaches to these phenotypes.
[Show abstract][Hide abstract] ABSTRACT: Background
Deciphering the genetic architecture of complex traits is still a major challenge for human genetics. In most cases, genome-wide association studies have only partially explained the heritability of traits and diseases. Epistasis, one potentially important cause of this missing heritability, is difficult to explore at the genome-wide level. Here, we develop and assess a tool based on interactive odds ratios (IOR), Fast Odds Ratio-based sCan for Epistasis (FORCE), as a novel approach for exhaustive genome-wide epistasis search. IOR is the ratio between the multiplicative term of the odds ratio (OR) of having each variant over the OR of having both of them. By definition, an IOR that significantly deviates from 1 suggests the occurrence of an interaction (epistasis). As the IOR is fast to calculate, we used the IOR to rank and select pairs of interacting polymorphisms for P value estimation, which is more time consuming.
FORCE displayed power and accuracy similar to existing parametric and non-parametric methods, and is fast enough to complete a filter-free genome-wide epistasis search in a few days on a standard computer. Analysis of psoriasis data uncovered novel epistatic interactions in the HLA region, corroborating the known major and complex role of the HLA region in psoriasis susceptibility.
Our systematic study revealed the ability of FORCE to uncover novel interactions, highlighted the importance of exhaustiveness, as well as its specificity for certain types of interactions that were not detected by existing approaches. We therefore believe that FORCE is a valuable new tool for decoding the genetic basis of complex diseases.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-015-0174-3) contains supplementary material, which is available to authorized users.
[Show abstract][Hide abstract] ABSTRACT: SUMMARY Models describing dengue epidemics are parametrized on disease incidence data and therefore high-quality data are essential. For Thailand, two different sources of long-term dengue data are available, the hard copy data from 1980 to 2005, where hospital admission cases were notified, and the electronic files, from 2003 to the present, where clinically classified forms of disease, i.e. dengue fever, dengue haemorrhagic fever, and dengue shock syndrome, are notified using separate files. The official dengue notification data, provided by the Bureau of Epidemiology, Ministry of Public Health in Thailand, were cross-checked with dengue data used in recent publications, where an inexact continuous time-series was observed to be consistently used since 2003, affecting considerably the model dynamics and its correct application. In this paper, numerical analysis and simulation techniques giving insights on predictability are performed to show the effects of model parametrization by using different datasets.
Epidemiology and Infection 11/2014; 142(11):2447-59. DOI:10.1017/S0950268813003348 · 2.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An expert conference on Dengue in Africa was held in Accra, Ghana, in February 2013 to consider key questions regarding the possible expansion of dengue in Africa. Four key action points were highlighted to advance our understanding of the epidemiology of dengue in Africa. First, dengue diagnostic tools must be made more widely available in the healthcare setting in Africa. Second, representative data need to be collected across Africa to uncover the true burden of dengue. Third, established networks should collaborate to produce these types of data. Fourth, policy needs to be informed so the necessary steps can be taken to provide dengue vector control and health services.
[Show abstract][Hide abstract] ABSTRACT: Dengue is a major international public health concern and the number of outbreaks has escalated greatly. Human migration, international trade and travel are constantly introducing new vectors and pathogens into novel geographic areas. Of particular interest is the extent to which dengue virus (DENV) infections are subclinical or inapparent. Not only may such infections contribute to the global spread of DENV by human migration, but also seroprevalence rates in naïve populations may be initially high despite minimal numbers of detectable clinical cases. As the probability of severe disease is increased in secondary infections, populations may thus be primed, with serious public health consequences following introduction of a new serotype. In addition, pre-existing immunity from inapparent infections may affect vaccine uptake and the ratio of clinically apparent to inapparent infection could affect the interpretation of vaccine trials. We performed a literature search for inapparent DENV infections and provide an analytical review of their frequency and associated risk factors. Inapparent rates were highly variable, but “inapparent” was the major outcome of infection in all prospective studies. Differences in the epidemiological context and type of surveillance account for much of the variability in inapparent infection rates. However, one particular epidemiological pattern was shared by four longitudinal cohort studies: the rate of inapparent DENV infections was positively correlated with the incidence of disease the previous year, strongly supporting an important role for short-term heterotypic immunity in determining the outcome of infection. Primary and secondary infections were equally likely to be inapparent. Knowledge of the extent to which viruses from inapparent infections are transmissible to mosquitoes is urgently needed. Inapparent infections need to be considered for their impact on disease severity, transmission dynamics, and vaccine efficacy and uptake.
Frontiers in Immunology 06/2014; 5:280. DOI:10.3389/fimmu.2014.00280
[Show abstract][Hide abstract] ABSTRACT: Additional file 1: Supplementary methods. Format: DOCX Size: 3.4MB
Additional file 2: Sources from which the datapoints in the maps were identified. Format: DOCX Size: 30KB
[Show abstract][Hide abstract] ABSTRACT: Additional file 4:
Map series 2: Africa. (A) Bar charts represent population surveys which examined the frequencies of selected G6PD variants in representative population samples. These population groups had not undergone prior G6PDd phenotype screening. The variants which were tested for in each location are listed above the x-axis. Sample size is stated under each plot. Survey locations are mapped to closest approximation at the point of origin of the plots; exact survey locations are shown in Panel B. (Panel A is reproduced from Figure 8 in the main manuscript).
Format: TIF Size: 4MB
[Show abstract][Hide abstract] ABSTRACT: Additional file 5:
Map series 2: Asia. Bar charts represent population surveys which examined the frequencies of selected G6PD variants in representative population samples. These population groups had not undergone prior G6PDd phenotype screening. The variants which were tested for in each location are listed above the x-axis. Survey locations are indicated by nearby black stars. Sample size is stated under each plot.
Format: TIF Size: 1.1MB
[Show abstract][Hide abstract] ABSTRACT: Additional file 3:
Map series 2: Americas. Bar charts represent population surveys which examined the frequencies of selected G6PD variants in representative population samples. These population groups had not undergone prior G6PDd phenotype screening. The variants which were tested for in each location are listed above the x-axis. Survey locations are indicated by nearby black stars. Sample size is stated under each plot.
Format: TIF Size: 691KB