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Background: The importance of remote infection with M.tuberculosis as a cause of tuberculosis disease (TB) is unclear, with limited evidence of impact on TB rates beyond 10 years. Our objective was to assess rates of tuberculosis over 30 years by M.tuberculosis infection status at baseline in Karonga District, Northern Malawi. Materials and methods: Population-based surveys of tuberculin skin testing (TST) from the 1980s were linked with follow-up and TB surveillance in Karonga district. We compared rates of microbiologically-confirmed TB by baseline TST induration <5mm (no evidence of M.tuberculosis infection) and those with baseline TST >17mm (evidence of M.tuberculosis infection), using hazard ratios by time since baseline and attributable risk percent. The attributable risk percent was calculated to estimate the proportion of TB in those infected that can be attributed to that prior infection. We analysed whole genome sequences of M.tuberculosis strains to identify recent transmission. Results: Over 412,959 person-years, 208 incident TB episodes were recorded. Compared to the small induration group, rates of TB were much higher in the first two years in the large induration group, and remained higher to 20 years: age, sex and area-adjusted hazard ratios (HR) 2–9 years post-TST 4.27 (95%CI 2.56–7.11); 10–19 years after TST 2.15 (1.10–4.21); ≥20 years post-TST 1.88 (0.76–4.65). The attributable risk percent of remote infection was 76.6% (60.9–85.9) 2–9 years post-TST, and 53.5% (9.1–76.2) 10–19 years post-TST. Individuals with large TST indurations had higher rates of unique-strain TB (HR adjusted for age, sex and area = HR 6.56 (95% CI 1.96–22.99)), suggesting disease following remote infection, but not of linked-strain TB (recent transmission). Conclusions: M.tuberculosis infection can increase the risk of TB far beyond 10 years, accounting for a substantial proportion of TB occurring among those remotely infected. [ABSTRACT FROM AUTHOR]

Katherine has plans that nicely combine already existing features of the journal with a variety of new initiatives that will extend the journal into new scholarly directions. After 2 years, Anthony moved on to serve as Editor of I Marriage and Family Review i and is doing very creative work for this journal as well. As my 4-year term ends, I have reflected on principles that I have learned from editing JFTR and how those principles apply across different professions and disciplines. [Extracted from the article]

Now that the global eradication of wild poliovirus is almost within sight, planning for the post-certification era is becoming a priority issue. It is agreed that a stockpile of appropriate polio vaccines will need to be established, and a surveillance and response capacity will need to be maintained, in order to protect the world against any possible future outbreaks attributable either to the persistence of wild poliovirus or vaccine-derived polioviruses (VDPVs) or to the unintentional or intentional release of poliovirus from a laboratory or vaccine store. Although it has been suggested that the stockpile should consist of monovalent oral poliovirus vaccine (mOPV), many questions remain concerning its nature, financing, management, and use - in particular, because of uncertainties over future national vaccination policies, and over the availability of different vaccines, after the certification of wild poliovirus eradication. There are further uncertainties concerning the possible role and efficacy of inactivated poliovirus vaccine (IPV) used either routinely or in outbreak control in low-hygiene settings, the potential for rapid geographical spread of polioviruses should an outbreak occur after certification, and the risks inherent in introducing additional oral polio vaccine (OPV) viruses into populations in which the vaccine coverage and prevalence of immunity have declined, and which may thus favour the spread of VDPVs. Given these important gaps in knowledge, no country should discontinue polio vaccination until a coordinated policy for the post-certification era has been developed and the recommended measures have been put in place.

OBJECTIVE: To estimate the impact of cotrimoxazole prophylaxis on the survival of human immunodeficiency virus (HIV)-positive tuberculosis (TB) patients. METHODS: A cohort study with a historical comparison group was conducted. End-of-treatment outcomes and 18-month survival were compared between TB patients registered in 1999 and patients registered in 2000 in Karonga District, Malawi. Case ascertainment, treatment and outpatient follow-up were identical in the two years except that in 2000 cotrimoxazole prophylaxis was offered to HIV-positive patients in addition to routine care. The prophylaxis was provided from the time a patient was identified as HIV-positive until 12 months after registration. Analyses were carried out on an intention-to-treat basis for all TB patients, and also separately by HIV status, TB type and certainty of diagnosis. FINDINGS: 355 and 362 TB patients were registered in 1999 and 2000, respectively; 70% were HIV-positive. The overall case fatality rate fell from 37% to 29%, i.e. for every 12.5 TB patients treated, one death was averted. Case fatality rates were unchanged between the two years in HIV-negative patients, but fell in HIV-positive patients from 43% to 24%. The improved survival became apparent after the first 2 months and was maintained beyond the end of treatment. The improvement was most marked in patients with smear-positive TB and others with confirmed TB diagnoses. CONCLUSION: Survival of HIV-positive TB patients improved dramatically with the addition of cotrimoxazole prophylaxis to the treatment regimen. The improvement can be attributed to cotrimoxazole because other factors were unchanged and the survival of HIV-negative patients was not improved. Cotrimoxazole prophylaxis should therefore be added to the routine care of HIV-positive TB patients.

Leprosy is a chronic infection of the skin and peripheral nerves caused by Mycobacterium leprae. Despite recent improvements in disease control, leprosy remains an important cause of infectious disability globally. Large-scale genetic association studies in Chinese, Vietnamese and Indian populations have identified over 30 susceptibility loci for leprosy. There is a significant burden of leprosy in Africa, however it is uncertain whether the findings of published genetic association studies are generalizable to African populations. To address this, we conducted a genome-wide association study (GWAS) of leprosy in Malawian (327 cases, 436 controls) and Malian (247 cases, 368 controls) individuals. In that analysis, we replicated four risk loci previously reported in China, Vietnam and India; MHC Class I and II, LACC1 and SLC29A3. We further identified a novel leprosy susceptibility locus at 10q24 (rs2015583; combined p = 8.81 × 10−9; OR = 0.51 [95% CI 0.40 − 0.64]). Using publicly-available data we characterise regulatory activity at this locus, identifying ACTR1A as a candidate mediator of leprosy risk. This locus shows evidence of recent positive selection and demonstrates pleiotropy with established risk loci for inflammatory bowel disease and childhood-onset asthma. A shared genetic architecture for leprosy and inflammatory bowel disease has been previously described. We expand on this, strengthening the hypothesis that selection pressure driven by leprosy has shaped the evolution of autoimmune and atopic disease in modern populations. More broadly, our data highlights the importance of defining the genetic architecture of disease across genetically diverse populations, and that disease insights derived from GWAS in one population may not translate to all affected populations. Author summary: Leprosy remains a leading cause of infectious disability globally. Human genetic variation is a major determinant of susceptibility to infection, including leprosy. Large-scale genetic association studies have been pivotal in advancing our understanding of leprosy biology. These studies have been performed in Chinese, Vietnamese and Indian populations, and it remains unclear whether these insights are informative of leprosy susceptibility in African populations. To address this, we performed a genome-wide association study of leprosy susceptibility in Malawi and Mali. In doing so we replicate known leprosy susceptibility loci at MHC class I and II, LACC1 and SLC29A3. Furthermore, we identify a novel leprosy susceptibility locus, which has been under recent selection pressure, which demonstrates pleiotropy with inflammatory bowel disease and atopic disease. We identify expression of ACTR1A in CD4+ T cells as candidate effector of leprosy risk at this locus. These data deepen our understanding of leprosy biology and further implicate this ancient pathogen in the evolution of immune-mediated diseases in modern populations. [ABSTRACT FROM AUTHOR]

The study attempts to evaluate the association, if any, between CISH polymorphisms and the susceptibility to infectious diseases. The results indicate that variants of CISH are associated with susceptibility to infectious disease and the overall risk of an infectious disease rose by nearly 18% in those carrying the variant CISH alleles.

The world's poorest children are likely to be malnourished when receiving their childhood vaccines. It is uncertain whether this affects vaccine efficacy and whether the coadministration of nutrient supplements with vaccines has beneficial of detrimental effects. More recently, a detrimental interaction between vitamin A (VA) supplementation (VAS) and the killed diphtheria-tetanus-pertussis vaccine given in early childhood has been suggested. This report provides a critical review of the published interactions between nutritional status and/or supplementation and vaccine responses in children. Due to an absence of evidence for most nutrients, this analysis focused on protein-energy, vitamins A and D, and iron and zinc. AII vaccines were considered. Both observational studies and clinical trials that led to peer-reviewed publications in English or French were included. These criteria led to a pool of 58 studies for protein-energy malnutrition, 43 for VA, 4 for vitamin D, 10 for iron, and 22 for zinc. Our analysis indicates that malnutrition has surprisingly little or no effect on vaccine responses. Evidence for definitive adjunctive effects of micronutrient supplementation at the time of vaccination is also weak. Overall, the paucity, poor quality, and heterogeneity of data make it difficult to draw firm conclusions. The use of simple endpoints that may not correlate strongly with disease protection adds uncertainty. A detailed examination of the immunological mechanisms involved in potential interactions, employing modern methodologies, is therefore required. This would also help us understand the proposed, but still unproven, negative interactions between VAS and vaccine safety, a resolution of which is urgently required. J. Nutr. 139: 2154S-2218S, 2009. doi: 10.3945/jn.109.105312

Tuberculosis patients with identical strains of Mycobacterium tuberculosis are described as clustered. Cluster size may depend on patient or strain characteristics. In a 7-year population-based study of tuberculosis in Karonga [...]

We conducted the first molecular study of tuberculosis (TB) to estimate the role of household contact and transmission from HIV-positive putative source contacts (PSCs) in a high HIV-prevalence area. TB [...]

A trial was conducted to assess whether the addition of standardized Burch colposuspension to abdominal sacrocolpopexy for the treatment of pelvic organ prolapse decreases postoperative stress urinary incontinence in women without preoperative symptoms of stress incontinence. It was found that in women without stress incontinence undergoing abdominal sacrocolpopexy for prolapse, Burch colposuspension significantly reduced postoperative symptoms of stress incontinence without increasing the lower urinary tract symptoms.

Environmental heterogeneity is considered to lead to specialization in plants and thereby contribute to the diversity of the tropical flora. The idea is examined on the basis of data on the habitat specificity of 35 western Amazonian species from the genera Protium, Crepidospermum, and Tetragastris in the monophyletic tribe Protieae mapped on a molecular-based phylogeny.

In a 7-year population-based study in Malawi, we showed that Beijing genotype tuberculosis (TB) increased as a proportion of TB cases. All the Beijing genotype strains were fully drug sensitive. [...]