This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards “pre-elimination” (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.

OBJECTIVE -After the demonstration that one-third of male patients with type 2 diabetes have hypogonadotrophic hypogonadism, we have shown that patients with hypogonadotrophic hypogonadism also have markedly elevated C-reactive protein (CRP) concentrations. We have now hypothesized that type 2 diabetic subjects with hypogonadotrophic hypogonadism may have a lower hematocrit because testosterone stimulates, whereas chronic inflammation suppresses, erythropoiesis.RESEARCH DESIGN AND METHODS -Seventy patients with type 2 diabetes at a tertiary referral center were included in this study.RESULTS -The mean hematocrit in patients with hypogonadotrophic hypogonadism (n ϭ 37), defined as calculated free testosterone (cFT) of Ͻ6.5 ng/dl, was 40.6 Ϯ 1.1%, whereas that in eugonadal patients (n ϭ 33) was 43.3 Ϯ 0.7% (P ϭ 0.011). The hematocrit was related to cFT concentration (r ϭ 0.46; P Ͻ 0.0001); it was inversely related to plasma CRP concentration (r ϭ 0.41; P Ͻ 0.0004). Patients with CRP Ͻ3 mg/l had a higher hematocrit (42.7 Ϯ 0.7%) than those with CRP Ͼ3 mg/l (39.9 Ϯ 1.1%; P Ͻ 0.05). The prevalence of normocytic normochromic anemia (hemoglobin Ͻ13 g/dl) was 23% in the entire group, whereas it was 37.8% in the men with hypogonadotrophic hypogonadism and 3% in the eugonadal men (P Ͻ 0.01). Erythropoietin concentration was elevated or high normal in all 11 patients with anemia in whom it was tested.CONCLUSIONS -We conclude that hypogonadotrophic hypogonadism in male type 2 diabetic subjects is associated with a lower hematocrit and a frequent occurrence of mild normocytic normochromic anemia with normal or high erythropoietin concentrations. In these patients, hematocrit is also inversely related to CRP concentration. Thus, low testosterone and chronic inflammatory mechanisms may contribute to mild anemia. Such patients may also have a high risk of atherosclerotic cardiovascular events in view of their markedly elevated CRP concentrations. Diabetes Care 29:2289 -2294, 2006A fter our previous observations that one-third of patients with type 2 diabetes have hypogonadotrophic hypogonadism (1), that type 1 diabetic subjects do not suffer from this condition (2), and that the patients with hypogonadotrophic hypogonadism have markedly elevated plasma C-reactive protein (CRP) concentrations (V.B., R.T., S.D., A. Chandel, A.C., H.G., P.D., unpublished observ a t i o n s ) , a n i n d e x o f s y s t e m i c inflammation, we have now studied whether patients with hypogonadotrophic hypogonadism have lower hemoglobin concentrations. Testosterone is known to exert a stimulatory effect on erythropoiesis in the bone marrow (3). Inflammation, on the other hand, is known to suppress erythropoiesis, partly through its direct action on erythropoiesis and partly through its suppression of erythropoietin secretion (4 -7). Thus, we hypothesized that hematocrit in patients with type 2 diabetes is lower in patients with hypogonadotrophic hypogonadism who also have an elevated CRP concentration, an index of systemic inflammation. RESEARCH DESI...

No abstract

Recent work shows a high prevalence of low testosterone and inappropriately low LH and FSH concentrations in type 2 diabetes. This syndrome of hypogonadotrophic hypogonadism (HH) is associated with obesity, and other features of the metabolic syndrome (obesity and overweight, hypertension and hyperlipidemia) in patients with type 2 diabetes. However, the duration of diabetes or HbA1c were not related to HH. Furthermore, recent data show that HH is also observed frequently in patients with the metabolic syndrome without diabetes but is not associated with type 1 diabetes. Thus, HH appears be related to the two major conditions associated with insulin resistance: type 2 diabetes and the metabolic syndrome. CRP concentrations have been shown to be elevated in patients with HH and are inversely related to plasma testosterone concentrations. This inverse relationship between plasma free testosterone and CRP concentrations in patients with type 2 diabetes suggests that inflammation may play an important role in the pathogenesis of this syndrome. This is of interest since inflammatory mechanisms may have a cardinal role in the pathogenesis of insulin resistance. It is relevant that in the mouse, deletion of the insulin receptor in neurons leads to HH in addition to a state of systemic insulin resistance. It has also been shown that insulin facilitates the secretion of gonadotrophin releasing hormone (GnRH) from neuronal cell cultures. Thus, HH may be the result of insulin resistance at the level of the GnRH secreting neuron. Low testosterone concentrations in type 2 diabetic men have also been related to a significantly lower hematocrit and thus to an increased frequency of mild anemia. Low testosterone concentrations are also related to an increase in total and regional adiposity, and to lower bone density. This review discusses these issues and attempts to make the syndrome relevant as a clinical entity. Clinical trials are required to determine whether testosterone replacement alleviates symptoms related to sexual dysfunction, and features of the metabolic syndrome, insulin resistance and inflammation.