Risk factors for drug resistant tuberculosis in Leicestershire - poor adherence to treatment remains an important cause of resistance

In the light of rising numbers of tuberculosis (TB) cases in the United Kingdom, the problem of anti-tubercular drug resistance remains a significant concern. Drug resistant TB cases are more difficult and costly to treat, and require appropriate treatment and control mechanisms. This matched case control study aimed to investigate risk factors for resistance in Leicestershire, using data for laboratory isolates of Mycobacterium tuberculosis identified from 1993 to 1998. Each case, defined as culture positive laboratory isolates resistant to at least one first-line drug, was matched to four fully sensitive controls on age, sex and ethnic group. Twenty-three cases and 81 controls were included in the analysis. Drug resistance in Leicestershire was found to be associated with poor adherence to treatment (OR 4(.)8, 95% CI 1(.)6-14(.)4, P=0(.)005) and with previous TB (OR 3(.)7, 95% CI 1(.)2-11(.)8, P=0(.)022). These findings emphasize the need to provide support to patients taking treatment in order to maximize adherence

Idiopathic AIDS enteropathy and treatment of gastrointestinal opportunistic pathogens.

Diarrhea in patients with acquired immune deficiency syndrome (AIDS) has proven to be both a diagnostic and treatment challenge since the discovery of the human immunodeficiency virus (HIV) virus more than 30 years ago. Among the main etiologies of diarrhea in this group of patients are infectious agents that span the array of viruses, bacteria, protozoa, parasites, and fungal organisms. In many instances, highly active antiretroviral therapy remains the cornerstone of therapy for both AIDS and AIDS-related diarrhea, but other targeted therapies have been developed as new pathogens are identified; however, some infections remain treatment challenges. Once identifiable infections as well as other causes of diarrhea are investigated and excluded, a unique entity known as AIDS enteropathy can be diagnosed. Known as an idiopathic, pathogen-negative diarrhea, this disease has been investigated extensively. Atypical viral pathogens, including HIV itself, as well as inflammatory and immunologic responses are potential leading causes of it. Although AIDS enteropathy can pose a diagnostic challenge so too does the treatment of it. Highly active antiretroviral therapy, nutritional supplementation, electrolyte replacements, targeted therapy for infection if indicated, and medications for symptom control all are key elements in the treatment regimen. Importantly, a multidisciplinary approach among the gastroenterologist, infectious disease physician, HIV specialists, oncology, and surgery is necessary for many patients

Regional and temporal changes in AIDS in Europe before HAART

In a prospective observational study 4485 patients from 46 clinical centres in 17 European countries were followed between April 1994 and November 1996. Information on AIDS-defining events (ADEs) were collected together with basic demographic data, treatment history and laboratory results. The centres were divided into four geographical regions (north, central, south-west and south-east) so that it was possible to identify any existing regional differences in ADEs. The regional differences that we observed included a higher risk of all forms of Mycobacterium tuberculosis infections (Tb) and wasting disease in the south-west and an increased risk of infections with the Mycobacterium avium complex (MAC) in the north. In Cox multivariable analyses, where north was used as the reference group, we observed hazard ratios of 6.87, 7.77, 2.29 and 0.16 (P < 0.05 in all cases) for pulmonary Tb, extrapulmonary Tb, wasting disease and MAC respectively in the south-west. Pneumocystis carinii pneumonia (PCP) was less commonly diagnosed in the central region (RH = 0.51, 95% CI 0.32-0.79, P = 0.003) and most common in the south-east (RH = 1.04, 95% CI 0.71-1.51, P = 0.85). Comparisons with a similar 'AIDS in Europe' study that concentrated on the early phase of the epidemic reveal that most of the regional differences that were observed in the 1980s still persist in the mid-1990s

The looming tide of nontuberculous mycobacterial infections in Portugal and Brazil

Nontuberculous mycobacteria (NTM) are widely disseminated in the environment and an emerging cause of infectious diseases worldwide. Their remarkable natural resistance to disinfectants and antibiotics and an ability to survive under low-nutrient conditions allows NTM to colonize and persist in man-made environments such as household and hospital water distribution systems. This overlap between human and NTM environments afforded new opportunities for human exposure, and for expression of their often neglected and underestimated pathogenic potential. Some risk factors predisposing to NTM disease have been identified and are mainly associated with immune fragilities of the human host. However, infections in apparently immunocompetent persons are also increasingly reported. The purpose of this review is to bring attention to this emerging health problem in Portugal and Brazil and to emphasize the urgent need for increased surveillance and more comprehensive epidemiological data in both countries, where such information is scarce and seriously thwarts the adoption of proper preventive strategies and therapeutic options.We acknowledge the support of FEDER through COMPETE and of National Funds through FCT - Fundacao para a Ciencia e a Tecnologia grants FCOMP-01-0124-FEDER-028359 [PTDC/BIA-MIC/2779/2012] and UID/NEU/04539/2013.info:eu-repo/semantics/publishedVersio

"Why me, why now?" Using clinical immunology and epidemiology to explain who gets nontuberculous mycobacterial infection

BACKGROUND: The prevalence of nontuberculous mycobacterial (NTM) disease is rising. An understanding of known risk factors for disease sheds light on the immunological and physical barriers to infection, and how and why they may be overcome. This review focuses on human NTM infection, supported by experimental and in vitro data of relevance to the practising clinician who seeks to understand why their patient has NTM infection and how to further investigate. DISCUSSION: First, the underlying immune response to NTM disease is examined. Important insights regarding NTM disease susceptibility come from nature's own knockouts, the primary immune deficiency disorders. We summarise the current knowledge surrounding interferon-gamma (IFNγ)-interleukin-12 (IL-12) axis abnormalities, followed by a review of phagocytic defects, T cell lymphopenia and rarer genetic conditions known to predispose to NTM disease. We discuss how these define key immune pathways involved in the host response to NTM. Iatrogenic immunosuppression is also important, and we evaluate the impact of novel biological therapies, as well as bone marrow transplant and chemotherapy for solid organ malignancy, on the epidemiology and presentation of NTM disease, and discuss the host defence dynamics thus revealed. NTM infection and disease in the context of other chronic illnesses including HIV and malnutrition is reviewed. The role of physical barriers to infection is explored. We describe how their compromise through different mechanisms including cystic fibrosis, bronchiectasis and smoking-related lung disease can result in pulmonary NTM colonisation or infection. We also summarise further associations with host factors including body habitus and age. We use the presented data to develop an over-arching model that describes human host defences against NTM infection, where they may fail, and how this framework can be applied to investigation in routine clinical practice

Mycobacterium avium resists exposure to the acidic conditions of the stomach

Organisms of the Mycobacterium avium complex are common pathogens in immunosuppressed patients such as individuals with AIDS. There is evidence that in AIDS patients, the main route for M. avium infection is the gastrointestinal tract. The stomach is a formidable barrier to pathogens and the ability to resist exposure to pH lower than 3 has been shown to be a virulence determinant of enteric pathogens. Incubation of three clinical isolates of M. avium under acidic pH revealed resistance of M. avium grown both to the exponential and stationary phase at pH 2.2 for 2 h. Inhibition of protein synthesis had no effect on the acid tolerance. When the duration of the incubation at pH 2.2 was extended to 24 h, bacteria grown to the stationary phase had a significantly greater tolerance to acid than exponential phase bacteria. M. avium incubated with acid in the presence of water was significantly more resistant to pH 2.2 than M. avium in the presence of buffer. Pre-adaptation in water prior to exposure to acidic conditions was also associated with increased resistance to pH 2.2. Isoosmolarity of Hank's balanced salt solution appears to be responsible for the impaired resistance to acid between 2 and 24 h of incubation. These findings indicate that M. avium is naturally tolerant to pH<3 and that pre-adaptation under conditions similar to the conditions where M. avium is found in the environment results in increased acid resistanc

Detection of Tropheryma whippelii DNA in a patient with AIDS

A case of an AIDS patient infected with the Whipple's disease bacterium, Tropheryma whippelii, is reported. A DNA fragment with sequence specificity for the 16S rRNA gene of the bacterium was detected by PCR in a duodenal biopsy specimen from a 55-year-old male patient with AIDS and diarrhea. The biopsy specimen contained periodic acid-Schiff stain-positive macrophages which did not, however, resemble the sickleform-particle-containing cells characteristic of Whipple's disease. This observation raises two possibilities: either the patient had a coincidence of AIDS and Whipple's disease or Tropheryma whippelii acted as an opportunistic pathogen in this immunodeficient patient. The latter explanation is of interest in light of the ongoing discussion of immunologic abnormalities as predisposing factors for Whipple's disease

Analysis of Research on the Effects of Improved Water, Sanitation, and Hygiene on the Health of People Living with HIV and AIDS and Programmatic Implications

This paper reviews the existing scientific and programmatic evidence, raises WASH issues in the HIV and AIDS context that need further study to build the evidence base, assesses current WASH guidance through a review of national HIV/AIDS guidelines from five African countries, and identifies programmatic implications that home-based care programs and the WASH sectors must consider