Glucocorticoids, 11beta-hydroxysteroid dehydrogenase, and fetal programming

Epidemiological studies in many distinct human populations have associated low weight or thinness at birth with a substantially increased risk of cardiovascular and metabolic disorders, including hypertension and insulin resistance/type 2 diabetes, in adult life. The concept of fetal "programming" has been advanced to explain this phenomenon. Prenatal glucocorticoid therapy reduces birthweight, and steroids are known to exert long-term organizational effects during specific "windows" of development. Therefore, we hypothesized that fetal overexposure to endogenous glucocorticoids might underpin the link between early life events and later disease. In rats, birthweight is reduced following prenatal exposure to the synthetic glucocorticoid dexamethasone, which readily crosses the placenta, or to carbenoxolone, which inhibits 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), the physiological feto-placental "barrier" to endogenous glucocorticoids. Although the offspring regain the weight deficit by weaning, as adults they exhibit permanent hypertension, hyperglycemia, and increased hypothalamic-pituitary-adrenal axis activity. Moreover, physiological variations in placental 11beta-HSD2 activity near term correlate directly with fetal weight. In humans, 11beta-HSD2 gene mutations produce a low birthweight, and some studies show reduced placental 11beta-HSD2 activity in association with intrauterine growth retardation. Moreover, low birthweight babies have higher plasma cortisol levels throughout adult life, indicating that hypothalamic-pituitary-adrenal axis programming also occurs in humans. The molecular mechanisms of glucocorticoid programming are beginning to be unraveled and involve permanent and tissue-specific changes in the expression of key genes, notably of the glucocorticoid receptor itself. Thus, glucocorticoid programming may explain, in part, the association between fetal events and subsequent disorders in adult life.     

Preventing recurrent tuberculosis in high HIV-prevalent areas in sub-Saharan Africa: what are the options for tuberculosis control programmes?

Several studies conducted in sub-Saharan Africa have pointed to an increased risk of recurrent TB in patients who are HIV-seropositive. Routine case notification data from the Malawi Tuberculosis Programme, which has improved its registration practices in the last two years, shows that recurrent TB (smear-positive and smear-negative TB) constitutes 9% of total notifications. The objectives of reducing rates of recurrent TB are 1) to complement other interventions to decrease TB incidence rates and transmission of disease, 2) to reduce TB-specific morbidity and mortality and 3) to restore confidence amongst health care staff and patients about the effectiveness of the current TB control strategy. Four possible options for reducing recurrent TB are discussed, and for each option this includes the evidence for effectiveness, current practice and operational considerations. The options are 1) using rifampicin and isoniazid (RH) in the continuation phase of treatment, 2) extending the duration of the continuation phase, 3) providing post-treatment isoniazid prophylaxis to HIV-positive patients who have completed treatment and 4) treating HIV-positive TB patients with highly active antiretroviral therapy (HAART). The last three options all require that TB patients know their HIV serostatus. The authors suggest that this issue of recurrent TB should be considered as one of the important areas for debate and action when considering the dual TB/HIV epidemic.     

Maximizing HIV partner notification opportunities for index patients and their sexual partners in Malawi

Introduction

HIV testing and counselling (HTC) is important to effect positive sexual behaviour change and is an entry point to treatment, care, and psychosocial support. One of the most practical initiatives to increase HTC is to encourage sexual partners of HIV-infected persons to test for HIV. However, partner notification strategies must be feasible in the healthcare setting and acceptable to the population.

Methods

We conducted a qualitative study during the pilot phase of an HIV partner notification trial to complement its assessment of feasibility and acceptability of methods of partner notification. We performed in-depth interviews with 16 consecutive HIV-positive index participants who consented and their 12 identifiable sexual partners. We also conducted two focus group discussions with healthcare workers to supplement the patient perspectives.In the main study, newly diagnosed HIV cases (index cases) were randomized to one of three methods of partner notification: passive, contract, and provider referral. Clients in the passive referral group were responsible for notifying their sexual partners themselves. Individuals in the contract referral group were given seven days to notify their partners, after which a healthcare provider contacted partners who had not reported for counselling and testing. In the provider group, a healthcare provider notified partners directly.

Results

Although most index participants and partners expressed a preference for passive notification, they also highlighted benefits for provider-assisted notification and the universal right for all HIV-exposed persons to know their HIV exposure and benefit from HIV testing and access antiretroviral treatment. Several participants mentioned couples counselling as a way to diffuse tension and get accurate information. All mentioned benefits to HIV testing, including the opportunity to change behaviour.

Conclusions

Provider-assisted partner notification is not preferred, but it is acceptable and may complement the passive method of notification. Couples counselling should also be encouraged.     

Poor attendance at a child TB contact clinic in Malawi.

SETTING: Child tuberculosis (TB) contact clinic, Queen Elizabeth Central Hospital, Blantyre, Malawi. DESIGN: Patients registered with smear-positive pulmonary TB (PTB) were encouraged to bring childhood household contacts to the clinic for assessment and management. Data of TB cases registered over the same period were collected from the Blantyre District TB Office. RESULTS: Attendance at the contact clinic was very poor, representing only 7.7% of all adults registered with smear-positive PTB over 17 months, and was significantly lower for potential male source cases than females (OR 0.36, 95% CI 0.23-0.55, P < 0.001). DISCUSSION: Improved uptake and implementation of child contact management in Malawi is a challenge.     

Prevalence and correlates of depression among HIV-infected and -affected older people in rural South Africa

Background

Little is known about depression in older people in sub-Saharan Africa, the associated impact of HIV, and the influence on health perceptions.

Objectives

Examine the prevalence and correlates of depression; explore the relationship between depression and health perceptions in HIV-infected and -affected older people.

Methods

In 2010, 422 HIV-infected and -affected participants aged 50+ were recruited into a cross-sectional study. Nurse professionals interviewed participants and a diagnosis of depressive episode was derived from the Composite International Diagnostic Interview (Depression module) using the International Classification of Diseases diagnostic criteria and categorised as major (MDE) or brief (BDE).

Results

Overall, 42.4% (n=179) had a depressive episode (MDE: 22.7%, n=96; BDE: 19.7%, n=83). Prevalence of MDE was significantly higher in HIV-affected (30.1%, 95% CI 24.0–36.2%) than HIV-infected (14.8%, 95% CI 9.9–19.7%) participants; BDE was higher in HIV-infected (24.6%, 95% CI 18.7–30.6%) than in HIV-affected (15.1%, 95% CI 10.3–19.8%) participants. Being female (aOR 3.04, 95% CI 1.73–5.36), receiving a government grant (aOR 0.34, 95% CI 0.15–0.75), urban residency (aOR 1.86, 95% CI 1.16–2.96) and adult care-giving (aOR 2.37, 95% CI 1.37–4.12) were significantly associated with any depressive episode. Participants with a depressive episode were 2–3 times more likely to report poor health perceptions.

Limitations

Study limitations include the cross-sectional design, limited sample size and possible selection biases.

Conclusions

Prevalence of depressive episodes was high. Major depressive episodes were higher in HIV-affected than HIV-infected participants. Psycho-social support similar to that of HIV treatment programmes around HIV-affected older people may be useful in reducing their vulnerability to depression.     

Predicting Partner HIV Testing and Counseling Following a Partner Notification Intervention

Provider-assisted methods of partner notification increase testing and counseling among sexual partners of patients diagnosed with HIV, however they are resource-intensive. The sexual partners of individuals enrolled in a clinical trial comparing different methods of HIV partner notification were analyzed to identify who was unlikely to seek testing on their own. Unconditional logistic regression was used to identify partnership characteristics, which were assigned a score based on their coefficient in the final model, and a risk score was calculated for each participant. The risk score included male partner sex, relationship duration 6-24 months, and index education > primary. A risk score of ≥ 2 had a sensitivity of 68% and specificity of 78% in identifying partners unlikely to seek testing on their own. A risk score to target partner notification can reduce the resources required to locate all partners in the community while increasing the testing yield compared to patient-referral.