Non-communicable diseases: harnessing the current opportunities.

Non-communicable diseases (NCDs) are receiving growing attention, which brings a unique opportunity to utilise solutions available to address them. These diseases are largely preventable; proven, cost-effective interventions are available; and when NCDs emerge, means exist to treat them, prevent complications, and to improve quality of life. Yet, there is a lack in progress in responding effectively to NCDs, and the current discussion and research focus predominantly on challenges rather than the opportunities, which this paper outlines.

Intake of total dietary sugar and fibre is associated with insulin resistance among Danish 8-10- and 14-16-year-old girls but not boys. European Youth Heart Studies I and II.

OBJECTIVE: To examine the dietary intake of total sugar, added sugar, non-added sugar and starch as well as dietary fibre and glycaemic index (GI) and their respective associations with insulin resistance. DESIGN: Mixed linear models were used to study both cross-sectional and prospective associations between carbohydrate components and insulin resistance separately in girls and boys. Diet was assessed by a single 24 h recall interview and insulin resistance was calculated using the homoestasis model assessment (HOMA). SETTING: The Danish part of the European Youth Heart Studies (EYHS) I and II. SUBJECTS: Girls and boys at 8-10 and 14-16 years from EYHS I (n 651) and 8-10-year-olds from baseline followed up 6 years later in EYHS II (n 233). RESULTS: Among girls, a difference in dietary total sugar of 43 g/MJ was associated with a 1 sd difference of HOMA and a difference in dietary fibre of -8 g/MJ was associated with a 1 sd difference of HOMA, independent of age, maturity and other confounders (both P = 0.03). No baseline associations were found among boys and no prospective associations were found in either sex. CONCLUSIONS: Dietary intake of total sugar may play an adverse role and fibre may play a beneficial role in concurrent insulin resistance among girls but not boys. Sex differences may be due to differences in maturity, physical activity, food patterns and selective reporting behaviours.

Intermittent preventive treatment of malaria in pregnancy: the effect of new delivery approaches on access and compliance rates in Uganda.

OBJECTIVE: To assess whether traditional birth attendants, drug-shop vendors, community reproductive health workers and adolescent peer mobilizers can administer intermittent preventive treatment (IPT) with sulfadoxine-pyremethamine to pregnant women, and reach those most at risk of malaria and increase access and compliance to it. METHODS: The study was designed to assess new approaches of delivering IPT through these groups and compare it with IPT at health units. The primary outcome measures were: the proportion of adolescents and primigravidae accessed; gestational age at recruitment and the proportion of women who completed two doses of sulfadoxine-pyremethamine. RESULTS: Two thousand seven hundred and eighty-five pregnant women (78% of those in the study area) participated. With new approaches, 92.4% of the women received IPT during the second trimester as recommended by the policy, vs. 76.1% at health units, P < 0.0001. Of the women who received two doses of sulfadoxine-pyremethamine, 39.9% were at health units (control) vs. 67.5% through new approaches (P < 0.0001). Women using the new approaches also accessed IPT early: the mean gestational age when receiving the first dose of sulfadoxine-pyremethamine was 21.0 weeks vs. 23.1 weeks at health units (P < 0.0001). However, the health units were used by a higher proportion of primigravidae (23.6% vs. 20.0%, P < 0.04), and this was also the case for adolescents (28.4% vs. 25.0%, P < 0.03). This intervention was acceptable with 89.1% of the women at the new approaches intending to use IPT in future. CONCLUSIONS: The new approaches increased access to and compliance with IPT. We recommend a review of the policy to allow the provision of IPT through the new approaches.

Atovaquone/proguanil resistance in Africa: a case report.

The Atovaquone/proguanil combination has quickly been established as an effective chemoprophylaxis for travellers to areas with chloroquineresistant Plasmodium falciparum malaria. We describe the molecular cause of the first reported case of primary Atovaquone/proguanil resistance observed in our department in a Plasmodium falciparum infected traveller returning from West Africa, and link our findings to other reports of resistance.

Chloroguanide metabolism in relation to the efficacy in malaria prophylaxis and the S-mephenytoin oxidation in Tanzanians.

S-Mephenytoin and chloroguanide (proguanil) oxidation was studied in 216 tanzanians. The mephenytoin S/R ratio in urine ranged from <0.1 to 1.16. The distribution was skewed to the right, without evidence of a bimodal distribution. Ten subjects (4.6%, 2.2% to 8.3%, 95% CI) with an S/R mephenytoin ratio >0.9, were arbitrarily defined as poor metabolizers of mephenytoin. The chloroguanide/cycloguanil ratio ranged from 0.82 to 249. There was a significant correlation between the mephenytoin S/R ratio and the chloroguanide/cycloguanil ratios (rs = 0.73; p<0.00001). This indicates that cytochrome P4502C19 or CYP2C19 is a major enzyme that catalyzes the bioactivation of chloroguanide to cycloguanil. Chloroguanide is a pro-drug, and hence a low CYP2C19 activity may lead to prophylactic failure caused by inadequate formation of cycloguanil. Fifty-eight women who previously took either 200 mg chloroguanide daily (n = 26) or 200 mg chloroguanide daily plus 300 mg chloroquine weekly (n = 32) in a malaria chemoprophylaxis study showed that there was significant correlation between the number of earlier breakthrough parasitemia episodes and the chloroguanide/cycloguanil ratio (rs = 0.30; p = 0.02). The breakthrough rate did not correlate with the S/R mephenytoin ratio. However, other factors, such as exposure to mosquitoes and sensitivity of the plasmodium to cycloguanil, are probably more important.

Oral candidiasis and hairy leukoplakia correlate with HIV infection in Tanzania.

We report a detailed study on oral lesions and their association with the WHO revised provisional case definition of AIDS as well as serologic signs of HIV infection among 186 patients in Dar Es Salaam, Tanzania. The patient material consisted of 39 hospitalized suspected AIDS patients, 44 medical nonsuspected patients, 53 dental outpatients, and 50 patients with sexually transmitted diseases. The male:female ratio was 2.1:1 on average. Oral examination was done without knowledge of the HIV status of the patients. Among 39 suspected AIDS patients 97% had WHO AIDS criteria and 90% were seropositive for HIV. Among the 147 patients not suspected of having AIDS 18 (12%) had AIDS criteria and 15% had serologic evidence of HIV infection. The presence of WHO AIDS criteria correlated significantly with the presence of HIV antibodies, but not with HIV antigen. Oral lesions were found in 54% of those with AIDS criteria and 52% of HIV-infected patients, as compared to 3% and 6% of the patients without AIDS criteria and HIV infection, respectively (p less than 0.01). Among patients with AIDS atrophic candidiasis occurred in 21%, pseudomembranous candidiasis in 23%, hairy leukoplakia in 36%, herpetic stomatitis in 2%, Kaposi's sarcoma in 4%, and nonspecific ulcer in 4%. The presence of oral lesions had a high predictive value for presence of AIDS criteria as well as for presence of HIV infection in this hospital setting. All patients should have a thorough oral examination and the presence of the aforementioned oral lesions should lead to testing for HIV infection.

HIV-induced immunodeficiency. Relatively preserved phytohemagglutinin as opposed to decreased pokeweed mitogen responses may be due to possibly preserved responses via CD2/phytohemagglutinin pathway.

We studied the proliferative response of PBL to the mitogens PHA and PWM and Candida albicans Ag in 301 HIV seropositive homosexual men, of whom 55 had AIDS. The responses to PHA were reduced only in the clinically ill HIV seropositive subjects. In contrast, the responses to PWM were profoundly reduced in most HIV seropositive subjects including the asymptomatic group. Further analysis of 16 HIV seropositive subjects showed that the proliferative responses were reduced in both CD4 and CD8 T cell subsets. A total of 15 HIV seropositive individuals with low responses to PWM, of whom seven had AIDS and eight controls were chosen for the following studies. Expression of T3, Ti, delta receptors, and CD2 was investigated and showed an increased percentage of CD2 receptors positive cells in HIV seropositive subjects without AIDS. The proliferative responses of PBL to stimulation with PHA, PWM, antibodies to CD3, or antibodies to CD2 were investigated and showed significant correlation in controls, whereas in contrast, only the responses to PHA and CD2ab correlated in patients with AIDS. The proliferative responses to CD2ab and CD3ab in controls were larger than the responses to both PHA and PWM. In patients, these responses were less suppressed than the responses to PWM indicating that stimulation with mitogens is more complex than a simple stimulation of Ti/T3 and CD2 receptors. Further investigations were done on resting T cells, i.e., lymphocytes depleted of macrophages and pre-activated cells. Addition of PHA to these cells resulted in preactivation with expression of IL-2R (CD25) but not in proliferation. In contrast, addition of PHA plus SRBC, which bind to the CD2 receptors caused IL-2R expression, IL-2 production, and proliferation. Addition of PWM + SRBC did not result in proliferation. A comparison of the responses to PHA + SRBC of resting T cells from 26 HIV seropositive individuals, of whom seven had AIDS and 12 seronegative controls, showed that these responses were normal or only slightly decreased in the 19 seropositive men without AIDS whereas it was decreased in AIDS patients. Nevertheless, all AIDS patients showed clear-cut responses in this assay. Thus, the discrepancy between responses to PHA and PWM may be explained by an at least partially preserved function of the PHA/CD2-dependent pathway. We suggest that the defect induced by the HIV infection primarily concerns T3/Ti-induced responses.