Household Costs of Leprosy Reactions (ENL) in Rural India

Background

Erythema nodosum leprosum (ENL) is a common immune-mediated complication of lepromatous (LL) and borderline lepromatous (BL) leprosy. Most patients experience chronic or multiple acute ENL over many years during an economically active period of their lives. Understanding the economic burden of ENL is essential to provide effective patient support, yet this area has not been investigated.

Methods

Ninety-one patients with LL or BL leprosy attending a leprosy hospital in Purulia district of West Bengal, India, were interviewed using a structured questionnaire. Cases (n = 53) were identified as those who had one or more episodes of ENL within the last 3 years. Controls (n = 38) had LL or BL leprosy but no history of ENL. Data were collected on household income, direct and indirect costs, and coping strategies.

Findings

The total household cost was Rs 1543 per month or 27.9% (IQR 13.2-52.6) of monthly household income for cases, and Rs 237 per month or 4.9% (IQR 1.7-13.4) of monthly household income for controls. Indirect costs accounted for 65% of total household costs for cases. Direct costs accounted for the remaining 35% of household costs, and resulted almost entirely from treatment-seeking in the private sector. Total household costs exceeded 40% of household income for 37.7% of cases (n = 20) and 2.6% of controls (n = 1) [1 USD = 59 INR].

Interpretation

Households affected by ENL face significant economic burden and are at risk of being pushed further into poverty. Health policy should acknowledge the importance of private sector provision and the significant contribution to total household costs of lost productivity (indirect cost). Further work is needed to explore this area and identify solutions.     

Comparing plasma and faecal measures of steroid hormones in Adelie penguins Pygoscelis adeliae

Physiological measurements of both stress and sex hormones are often used to estimate the consequences of natural or human-induced change in ecological studies of various animals. Different methods of hormone measurement exist, potentially explaining variation in results across studies; methods should be cross-validated to ensure that they correlate. We directly compared faecal and plasma hormone measurements for the first time in a wild free-living species, the Adelie penguin (Pygoscelis adeliae). Blood and faecal samples were simultaneously collected from individual penguins for comparison and assayed for testosterone and corticosterone (or their metabolites). Sex differences and variability within each measure, and correlation of values across measures were compared. For both hormones, plasma samples showed greater variation than faecal samples. Males had higher mean corticosterone concentrations than females, but the difference was only statistically significant in faecal samples. Plasma testosterone, but not faecal testosterone, was significantly higher in males than females. Correlation between sample types was poor overall, and weaker in females than in males, perhaps because measures from plasma represent hormones that are both free and bound to globulins, whereas measures from faeces represent only the free portion. Faecal samples also represent a cumulative measure of hormones over time, as opposed to a plasma ‘snapshot’ concentration. Our data indicate that faecal sampling appears more suitable for assessing baseline hormone concentrations, whilst plasma sampling may best define immediate responses to environmental events. Consequently, future studies should ensure that they select the most appropriate matrix and method of hormone measurement to answer their research questions.     

How can malaria rapid diagnostic tests achieve their potential? A qualitative study of a trial at health facilities in Ghana

Malaria is still a major public health problem in Brazil, with approximately 306 000 registered cases in 2009, but it is estimated that in the early 1940s, around six million cases of malaria occurred each year. As a result of the fight against the disease, the number of malaria cases decreased over the years and the smallest numbers of cases to-date were recorded in the 1960s. From the mid-1960s onwards, Brazil underwent a rapid and disorganized settlement process in the Amazon and this migratory movement led to a progressive increase in the number of reported cases. Although the main mosquito vector (Anopheles darlingi) is present in about 80% of the country, currently the incidence of malaria in Brazil is almost exclusively (99,8% of the cases) restricted to the region of the Amazon Basin, where a number of combined factors favors disease transmission and impair the use of standard control procedures. Plasmodium vivax accounts for 83,7% of registered cases, while Plasmodium falciparum is responsible for 16,3% and Plasmodium malariae is seldom observed. Although vivax malaria is thought to cause little mortality, compared to falciparum malaria, it accounts for much of the morbidity and for huge burdens on the prosperity of endemic communities. However, in the last few years a pattern of unusual clinical complications with fatal cases associated with P. vivax have been reported in Brazil and this is a matter of concern for Brazilian malariologists. In addition, the emergence of P. vivax strains resistant to chloroquine in some reports needs to be further investigated. In contrast, asymptomatic infection by P. falciparum and P. vivax has been detected in epidemiological studies in the states of Rondonia and Amazonas, indicating probably a pattern of clinical immunity in both autochthonous and migrant populations. Seropidemiological studies investigating the type of immune responses elicited in naturally-exposed populations to several malaria vaccine candidates in Brazilian populations have also been providing important information on whether immune responses specific to these antigens are generated in natural infections and their immunogenic potential as vaccine candidates. The present difficulties in reducing economic and social risk factors that determine the incidence of malaria in the Amazon Region render impracticable its elimination in the region. As a result, a malaria-integrated control effort - as a joint action on the part of the government and the population - directed towards the elimination or reduction of the risks of death or illness, is the direction adopted by the Brazilian government in the fight against the disease.     

Development of a host-genotype-independent counterselectable marker and a high-frequency conjugative delivery system and their use in genetic analysis of Enterococcus faecalis

Enterococcus faecalis is a gram-positive commensal bacterium of the gastrointestinal tract. E. faecalis is also an opportunistic pathogen that frequently exhibits resistance to available antibiotics. Despite the clinical significance of the enterococci, genetic analysis has been restricted by limitations inherent in the available genetic tools. To facilitate genetic manipulation of E. faecalis, we developed a conjugative delivery system for high-frequency introduction of cloned DNA into target strains of E. faecalis and a host-genotype-independent counterselectable marker for use in markerless genetic exchange. We used these tools to construct a collection of E. faecalis mutant strains carrying defined mutations in several genes, including ccfA, eep, gelE, sprE, and an alternative sigma factor (sigH). Furthermore, we combined these mutations in various permutations to create double mutants, triple mutants, and a quadruple mutant of E. faecalis that enabled tests of epistasis to be conducted on the pheromone biosynthesis pathway. Analysis of cCF10 pheromone production by the mutants revealed that both the ccfA2 and delta eep10 mutations are epistatic to mutations in gelE/sprE. To our knowledge, this represents the first example of epistasis analysis applied to a chromosomally encoded biosynthetic pathway in enterococci. Thus, the advanced tools for genetic manipulation of E. faecalis reported here enable efficient and sophisticated genetic analysis of these important pathogens.     

Carrier rates of the ancestral Indian W24X mutation in GJB2 in the general Gypsy population and individual subisolates

Mutations in the GJB2 gene are the most common cause of autosomal recessive nonsyndromic hearing loss and occur in approximately 20% of all cases of prelingual deafness. Previous studies of Roma/Gypsies in Slovakia, the Czech Republic, and Spain have shown that W24X, the most common GJB2 mutation in India, is also the prevalent molecular defect in the Gypsy population. The reported W24X frequencies vary broadly from 23% to 93% of Gypsy mutant alleles, likely reflecting local founder effects, drift, and differential admixture in the subisolates of this genetically structured population. Our goal was to provide more representative data on W24X carrier rates in European Gypsies, which can inform individual diagnostic investigations and public health initiatives across countries. Mutation testing in 603 control subjects of Gypsy ethnicity, representing 8 traditional subisolates in southeastern Europe and 4 additional European regions revealed that W24X is spread across subisolates, as expected for an ancestral founder mutation. While variation between subisolates does exist, the average carrier rates, overall and in the major linguistic/migrational categories of Balkan Gypsies, Vlax Roma, and west European Gypsies, are consistently in the 4%-5% range. The results place W24X among the three most common founder mutations in the Gypsies, and classify them as one of the high-risk populations for prelingual deafness. Higher demands on language acquisition in this bilingual population, together with poorer quality of health care compared to autochthonous Europeans, make the consequences of congenital deafness even more damaging than is usually the case. Neonatal screening for W24X among Gypsies would be a justified and cost-effective public health intervention.     

Oligonucleotide microarray identification of Bacillus anthracis strains using support vector machines

The capability of a custom microarray to discriminate between closely related DNA samples is demonstrated using a set of Bacillus anthracis strains. The microarray was developed as a universal fingerprint device consisting of 390 genome-independent 9mer probes. The genomes of B. anthracis strains are monomorphic and therefore, typically difficult to distinguish using conventional molecular biology tools or microarray data clustering techniques. Using support vector machines (SVMs) as a supervised learning technique, we show that a low-density fingerprint microarray contains enough information to discriminate between B. anthracis strains with 90% sensitivity using a reference library constructed from six replicate arrays and three replicates for new isolates.