Notification of rheumatic fever in South Africa -- evidence for underreporting by health care professionals and administrators.

OBJECTIVE: To determine whether under-reporting of rheumatic fever occurs at hospital, municipal, provincial and national levels of the South African health system. BACKGROUND: Information on the incidence of rheumatic fever (RF) and the prevalence of rheumatic heart disease (RHD) is required for the prevention of valvular heart disease in developing countries. In South Africa, RF was made a notifiable condition in 1989. It has recently been suggested that the reporting of RF cases may be incomplete, possibly because of underreporting by health care professionals and deficient administration of the disease notification system in South Africa. METHOD AND RESULTS: We assessed whether underreporting of RF cases occurs by comparing the numbers of RF cases reported per year at hospital, municipal, provincial and national levels from 1990 to 2004. There was a fall in the number of RF cases reported per year at national and provincial level over the 15 years of observation. A detailed analysis of the number of RF cases reported at hospital, municipal and provincial level for a 5-year period showed that more cases were diagnosed in one hospital (serving a smaller population) than were captured at municipal and provincial level (serving a larger population), suggesting underreporting by health care professionals. There were discrepancies in the number of cases reported at municipal, provincial and national level, suggesting poor administration of the notification system. CONCLUSION: There appears to be underreporting of RF cases by health care professionals, and poor administration of the RF notification system. Health care professionals need to be educated about the statutory requirement to notify all RF cases in South Africa. An effective national disease notification system is required.     

A rare variant of the leptin gene has large effects on blood pressure and carotid intima-medial thickness: a study of 1428 individuals in 248 families

Background: Rare mutations in the leptin (LEP) gene cause severe obesity. Common polymorphisms of LEP have been associated with obesity, but their association with cardiovascular disease has been little studied. We have examined the impact of both common and rare polymorphisms of the LEP gene on blood pressure (BP), subclinical atherosclerosis as measured by carotid intima-medial thickness (CIMT), and body mass index (BMI) in a large family study.

Methods: Five polymorphisms spanning LEP were typed in 1428 individuals from 248 nuclear families. BP, CIMT, BMI, and plasma leptin were measured.

Results: The polymorphisms typed captured all common haplotypes present at LEP. There was strong association between a rare polymorphism in the 3' untranslated region of LEP (C538T) and both pulse pressure (p = 0.0001) and CIMT (p = 0.008). C/T heterozygotes had a 22% lower pulse pressure and a 17% lower CIMT than C/C homozygotes. The polymorphism accounted for 3–5% of the population variation in pulse pressure and CIMT. There was no association between any LEP polymorphism and either BMI or plasma leptin level.

Conclusions: This large family study shows that the rare T allele at the C538T polymorphism of LEP substantially influences pulse pressure and CIMT, but does not appear to exert this effect through actions on plasma leptin level or BMI. This suggests that autocrine or paracrine effects in vascular tissue may be important physiological functions of leptin. This study also provides evidence that rare polymorphisms of particular genes may have substantial effects within the normal range of certain quantitative traits.

     

Characteristics and survival for HIV-associated multicentric Castleman disease in Malawi

Introduction

Clinical reports of multicentric Castleman disease (MCD) from sub-Saharan Africa (SSA) are scarce despite high prevalence of HIV and Kaposi sarcoma-associated herpesvirus (KSHV). Our objective is to describe characteristics and survival for HIV-associated MCD patients in Malawi. To our knowledge, this is the first HIV-associated MCD case series from the region.

Methods

We describe HIV-positive patients with MCD in Lilongwe, and compare them to HIV-associated lymph node Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) patients treated at our centre. All patients were enrolled into a prospective longitudinal cohort study at a national teaching hospital and cancer referral centre serving half of Malawi''s 16 million people. We included adult patients≥18 years of age with HIV-associated MCD (n=6), lymph node KS (n=5) or NHL (n=31) enrolled between 1 June 2013 and 31 January 2015.

Results and discussion

MCD patients had a median age of 42.4 years (range 37.2–51.8). All had diffuse lymphadenopathy and five had hepatosplenomegaly. Concurrent KS was present for one MCD patient, and four had performance status ≥3. MCD patients had lower median haemoglobin (6.4 g/dL, range 3.6–9.3) than KS (11.0 g/dL, range 9.1–12.0, p=0.011) or NHL (11.2 g/dL, range 4.5–15.1, p=0.0007). Median serum albumin was also lower for MCD (2.1 g/dL, range 1.7–3.2) than KS (3.7 g/dL, range 3.2–3.9, p=0.013) or NHL (3.4 g/dL, range 1.8–4.8, p=0.003). All six MCD patients were on antiretroviral therapy (ART) with median CD4 count 208 cells/µL (range 108–1146), and all with HIV RNA <400 copies/mL. Most KS and NHL patients were also on ART, although ART duration was longer for MCD (56.4 months, range 18.2–105.3) than KS (14.2 months, range 6.8–21.9, p=0.039) or NHL (13.8 months, range 0.2–98.8, p=0.017). Survival was poorer for MCD patients than lymph node KS or NHL.

Conclusions

HIV-associated MCD occurs in Malawi, is diagnosed late and is associated with high mortality. Improvements in awareness, diagnostic facilities, treatment and supportive care are needed to address this likely under-recognized public health problem in SSA.     

Pharmacokinetics and Pharmacodynamics of Clofazimine in a Mouse Model of Tuberculosis

The antileprosy drug clofazimine has shown potential for shortening tuberculosis treatment; however, the current dosing of the drug is not evidence based, and the optimal dosing is unknown. Our objective was to conduct a preclinical evaluation of the pharmacokinetics and pharmacodynamics of clofazimine in the mouse model of tuberculosis, with the goal of providing useful information on dosing for future studies. Pharmacokinetic parameters were evaluated in infected and uninfected BALB/c mice. Pharmacodynamic parameters were evaluated in Mycobacterium tuberculosis-infected mice that were treated for 12 weeks with one of six different clofazimine dosing regimens, i.e., doses of 6.25, 12.5, and 25 mg/kg of body weight/day and 3 regimens with loading doses. Clofazimine progressively accumulated in the lungs, livers, and spleens of the mice, reaching levels of greater than 50 μg/g in all tissues by 4 weeks of administration, while serum drug levels remained low at 1 to 2 μg/ml. Elimination of clofazimine was extremely slow, and the half-life was dependent on the duration of drug administration. Clofazimine exhibited dose-dependent tissue and serum concentrations. At any dose, clofazimine did not have bactericidal activity during the first 2 weeks of administration but subsequently demonstrated potent, dose-independent bactericidal activity. The antituberculosis activity of clofazimine was dependent on neither the dose administered nor the drug concentrations in the tissues, suggesting that much lower doses could be effectively used for tuberculosis treatment.     

Metformin and heart failure–related outcomes in patients with or without diabetes: a systematic review of randomized controlled trials

Heart Failure Reviews - Metformin is considered a safe anti-hyperglycemic drug for patients with type 2 diabetes (T2D); however, information on its impact on heart failure–related outcomes...     

Pancreatic β-cell dysfunction in type 2 diabetes: Implications of inflammation and oxidative stress

Insulin resistance and pancreatic β-cell dysfunction are major pathological mechanisms implicated in the development and progression of type 2 diabetes(T2D). Beyond the detrimental effects of insulin resistance, inflammation and oxidative stress have emerged as critical features of T2D that define β-cell dysfunction. Predominant markers of inflammation such as C-reactive protein, tumor necrosis factor alpha, and interleukin-1β are consistently associated with β-cell failure in preclinical models...     

A hybrid form of cardiac resynchronisation therapy in patients with failing systemic right ventricles

INTRODUCTION: Late systemic right ventricular (RV) dysfunction after atrial redirection surgery is common. Patients may require cardiac transplantation in early adulthood. METHODS: We undertook cardiac resynchronisation (CRT)/defibrillator therapy in two patients as a bridge to transplantation. RESULTS: Two males (aged 24, 110 kg and 26 years, 106 kg); having undergone a Mustard procedure for dextro-transposition of the great arteries at 7 and 6 months of age respectively, presented with impaired systemic RV function and New York Heart Association III symptoms. Both patients had dual chamber pacemakers in-situ for sinus bradycardia. Upgrade to CRT was performed by conserving the existing endocardial leads and placement of epicardial electrodes. One demonstrated sustained improvement over a 24 month follow-up period. CONCLUSION: A hybrid CRT strategy is feasible in patients with failing systemic RVs and pre-existent endocardial dual chamber pacemakers. Appropriate patient selection criteria and optimum lead placement, however, still needs further evaluation in this population.     

Utilization of implantable defibrillators in Africa

Sub-Saharan Africa is dominated by diseases of poverty. HIV/AIDS affects 28.5 out of a total of 600 million in the region. South Africa is the only country in sub-Saharan Africa in which implantable cardiovertor defibrillators (ICDs) are implanted (0.8/million in 2001). Only 3 of the 35 new ICDs were implanted in state-funded public hospitals. The pacemaker implantation rate for South Africa was 41/million in 2001. Approximately 20% of the population consume 56% of the health care expenditure, mainly funded by Medical Insurance. A tax-funded state health care system serves the rest of the population, but is concentrated on improving sanitation and primary health care. Diversion of funds from academic tertiary hospitals has reduced specialised services, particularly cardiology and cardiac surgery, and has resulted in an exodus of skilled personnel to the private sector. In the rest of sub-Saharan Africa, tertiary health care is mainly privately funded. Cardiology and cardiac surgery is not widely available. Many countries are crippled by debt and chronic local conflicts.Only one state hospital (Groote Schuur, Cape Town) provides an electrophysiology (EP) service including catheter ablation and ICD implantation, and training in EP, by two electrophysiologists. EP services are available privately in 3 centres. No EP service exists in the rest of sub-Saharan Africa.