Operational research leading to rapid national policy change: tuberculosis-diabetes collaboration in India

In 2011, bi-directional screening for tuberculosis (TB) and diabetes mellitus (DM) was recommended by the World Health Organization (WHO), although how best to implement the activity was not clear. In India, with early engagement of national programme managers and all important stakeholders, a countrywide, multicentre operational research (OR) project was designed in October 2011 and completed in 2012. The results led to a rapid national policy decision to routinely screen all TB patients for DM in September 2012. The process, experience and enablers of implementing this unique and successful collaborative model of operational research are presented.     

Sex,drugs and prisons: HIV prevention strategies for over 190 000 clients in Ukraine

Setting: One hundred and forty non-governmental organisations implementing human immunodeficiency virus (HIV) prevention programmes among clients, including people who inject drugs, prisoners, female sex workers, men who have sex with men and street children in Ukraine, 2010–2011.Objective: Among enrolled clients, to assess factors associated with HIV testing, HIV retesting within a year of initial testing and HIV seroconversion.Design: Retrospective cohort study involving record reviews.Results: Of 192 487 clients, 42 109 (22%) underwent an initial HIV test (22% were positive). Among HIV-negative clients at baseline, 10 858 (27%) were retested within a year: 317 (3%) of these were HIV-positive. HIV testing and retesting rates were lower among prisoners (0.3%) and others (street children and partners of those in risk groups, 6%), and those who did not receive counselling or services such as condom and needle distribution. Individuals who were not counselled were more likely to seroconvert.Conclusions: In this large cohort of high-risk groups from Eastern Europe, HIV testing was low and HIV sero-conversion was high. This is of public health concern, bringing into question the overall quality of counselling and how well it is tailored to the specific needs of various risk groups. Qualitative studies to understand the reasons for non-testing are urgently required for designing client-specific interventions.     

Integrating tuberculosis and HIV services in rural Kenya: uptake and outcomes

Setting: Seventeen rural public health facilities in Western Kenya that introduced three models of integrated care for tuberculosis (TB) and human immunodeficiency virus (HIV) patients.Objective: To assess the uptake and timing of cotrimoxazole preventive therapy (CPT) and antiretroviral treatment (ART) as well as anti-tuberculosis treatment outcomes among HIV-infected TB patients before (March–October 2010) and after (March–October 2012) the introduction of integrated TB-HIV care.Design: A before-and-after cohort study using programme data.Results: Of 501 HIV-infected TB patients, 357 (71%) were initiated on CPT and 178 (39%) on ART in the period before the introduction of integrated TB-HIV care. Following the integration of services, respectively 316 (98%) and 196 (61%) of 323 HIV-infected individuals were initiated on CPT and on ART (P < 0.001). The median time to CPT and ART initiation dropped from 7 to 2 days and from 42 to 34 days during the pre- and post-integration phases, respectively. Overall TB success rates did not vary with integration or with type of model instituted.Conclusion: Integration of TB and HIV services enhanced uptake and reduced delay in instituting CPT and ART in rural health facilities. There is a need to increase impetus in these efforts.     

WHO clinical staging of HIV infection and disease, tuberculosis and eligibility for antiretroviral treatment: relationship to CD4 lymphocyte counts.

SETTING: Thyolo district, Malawi. OBJECTIVES: To determine in HIV-positive individuals aged over 13 years CD4 lymphocyte counts in patients classified as WHO Clinical Stage III and IV and patients with active and previous tuberculosis (TB). DESIGN: Cross-sectional study. METHODS: CD4 lymphocyte counts were determined in all consecutive HIV-positive individuals presenting to the antiretroviral clinic in WHO Stage III and IV. RESULTS: A CD4 lymphocyte count of < or = 350 cells/microl was found in 413 (90%) of 457 individuals in WHO Stage III and IV, 96% of 77 individuals with active TB, 92% of 65 individuals with a history of pulmonary TB (PTB) in the last year, 91% of 89 individuals with a previous history of PTB beyond 1 year, 81% of 32 individuals with a previous history of extra-pulmonary TB, 93% of 107 individuals with active or past TB with another HIV-related disease and 89% of 158 individuals with active or past TB without another HIV-related disease. CONCLUSIONS: In our setting, nine of 10 HIV-positive individuals presenting in WHO Stage III and IV and with active or previous TB have CD4 counts of < or = 350 cells/microl. It would thus be reasonable, in this or similar settings where CD4 counts are unavailable for clinical management, for all such patients to be considered eligible for antiretroviral therapy.     

Maintenance zinc therapy after initial penicillamine chelation to treat symptomatic hepatic Wilson’s disease in resource constrained setting

Background

Experience with zinc in treating symptomatic hepatic Wilson’s disease (WD) is limited.

Aim

To study the efficacy of Penicillamine followed by zinc in treating symptomatic hepatic Wilson’s disease.

Methods

We retrospectively analyzed case records of 31 symptomatic hepatic WD patients for whom disease severity scores (Child’s, model for end-stage liver disease (MELD), Nazer’s, and New Wilson Index (NWI) score) and 24-h urinary copper were compared at 3-time points—baseline at presentation, at transition from penicillamine to zinc and at end of follow up.

Results

Thirty-one patients (median age 11 [5–24] years) with symptomatic hepatic WD were studied; ten had associated neuropsychiatric manifestations of WD. Penicillamine was changed to zinc sulfate either due to financial constraints (28 patients) or due to adverse effects of penicillamine (3 patients). At presentation (baseline), six patients belonged to Child’s class A, five to Child’s B, and 17 to Child’s C. Duration of initial penicillamine chelation therapy was 134 (2–320) weeks, and of subsequent zinc therapy was 363 (35–728) weeks. There was a significant improvement in liver function tests and disease severity scores (Child’s, MELD, Nazer’s, and NWI score) at the transition from penicillamine to zinc compared to baseline. This improvement was maintained until the end of study period with 90% survival at 10 (2–20) years. Fifteen of the 17 Child’s C cirrhotic patients showed significant improvement in disease severity scores from baseline until end of follow up.

Conclusions

Penicillamine followed by zinc may be a safe and effective treatment in resource-constrained setting for symptomatic hepatic WD patients in all grades of baseline disease severity. Some patients with decompensated cirrhosis due to WD may be managed with medical treatment, avoiding liver transplantation.

     

Prevalence, correlates, awareness, treatment, and control of hypertension in a middle-aged urban population in Kerala

BACKGROUND: Hypertension is an important cause of cardiovascular morbidity and mortality. METHODS AND RESULTS: We conducted a cross-sectional survey of 314 middle-aged subjects (163 men; age range 40-60 years, mean 49 years) in urban Thiruvananthapuram City. Kerala, to estimate the prevalence of hypertension, examine its correlates, and assess the degree of awareness, treatment, and control of high blood pressure. Blood pressure was measured by a nurse graduate using a mercury column sphygmomanometer and a standardized technique. We used multivariable analyses to examine the sociodemographic and clinical correlates of hypertension. The overall prevalence of hypertension in our sample was 54.5% (men 56.3%, women 52.3%). The factors associated with an increased prevalence of hypertension were higher body-mass index (odds ratio for a value in the top tertile of 2.33, 95% confidence interval: 1.2-4.4), and older age (odds ratio for the age group 55-60 years of 2.65, 95% confidence interval: 1.3-5.6). An occupation involving moderate or greater physical activity was inversely associated with the prevalence of hypertension (odds ratio 0.35, 95% confidence interval 0.13-0.94). Among hypertensives, 39% were aware of the condition, while 29% were treated with blood pressure-lowering medications. Adequate control of elevated blood pressure was achieved in only 30.6% of treated hypertensives. In our community-based sample, over half of all middle-aged individuals were hypertensive, but less than a third were under treatment. Adequate control of hypertension was achieved in less than a third of the treated individuals. CONCLUSIONS: These observations re-emphasize the need for hypertension awareness programs targeting the general public and the increased use of opportunistic blood pressure screening, and underscore the importance of measures to increase the knowledge of current guidelines for the detection and treatment of hypertension among healthcare providers.     

Short-term heart variability and oxidative stress in newly diagnosed essential hypertension

We sought to evaluate oxidative stress parameters like malondialdehyde, total antioxidant status, and time, frequency domain heart rate variability indices in newly diagnosed untreated hypertension. We also sought to study the correlation between heart rate variability and oxidative stress parameters in normotensive and newly diagnosed untreated essential hypertensives. Fourteen normotensive males and 36 newly diagnosed male hypertensives were enrolled for the study. Malondialdehyde, total antioxidant status, and heart rate variability in the frequency and time domain were studied in the hypertensive and normotensive group. Malondialdehyde was significantly higher in the hypertensive group, whereas total antioxidant status was significantly higher in the control group. SDNN, RR triangular index, RMSSD, log(10) low-frequency power, log (10) high-frequency power, log (10) total power, and heart rate variability during deep breathing test was significantly lower in hypertensive patients compared to normotensive controls. SDNN, RMSSD, high-frequency power, and high-frequency power normalized had significant negative correlation with malondialdehyde. Low-frequency power normalized positively correlated with malondialdehyde. Total antioxidant status had a significant negative correlation with blood pressure. The study gives further evidence for a decreased heart rate variability and elevated oxidative stress in hypertension.     

TREX1 D18N mice fail to process erythroblast DNA resulting in inflammation and dysfunctional erythropoiesis

Abstract

Anaemia is commonly observed in chronic inflammatory conditions, including systemic lupus erythematosus (SLE), where ～50% of patients display clinical signs of anaemia. Mutation at the aspartate residue 18 of the three prime repair exonuclease 1 (TREX1) gene causes a monogenic form of cutaneous lupus in humans and the genetically precise TREX1 D18N mice recapitulate a lupus-like disease. TREX1 degrades single- and double-stranded DNA (dsDNA), and the link between failed DNA degradation by nucleases, including nucleoside-diphosphate kinases (NM23H1/H2) and Deoxyribonuclease II (DNase II), and anaemia prompted our studies to investigate whether TREX1 dysfunction contributes to anaemia. Utilizing the TREX1 D18N mice we demonstrate that (1) TREX1 mutant mice develop normocytic normochromic anaemia and (2) TREX1 exonuclease participates in the degradation of DNA originating from erythroblast nuclei during definitive erythropoiesis. Gene expression, hematocrit, hemoglobin, immunohistochemistry (IHC) and flow cytometry were used to quantify dysfunctional erythropoiesis. An altered response to induced anaemia in the TREX1 D18N mice was determined through IHC, flow cytometry, and interferon-stimulated gene (ISG) expression analysis of the liver, spleen and erythroblastic islands (EBIs). IHC, flow cytometry, and ISG expression studies were performed in vitro to determine the role of TREX1 in the degradation of erythroblast DNA within EBIs. The TREX1 D18N mice exhibit altered erythropoiesis including a 20% reduction in hematocrit, 10–20 fold increased erythropoietic gene expression levels in the spleen and phenotypic signs of normocytic normochromic anaemia. Anaemia in TREX1 D18N mice is accompanied by increased erythropoietin (Epo), normal hepcidin levels and the TREX1 D18N mice display an inappropriate response to anaemic challenge. Enhanced ISG expression results from failed processing and subsequent sensing of undegraded erythroblast DNA in EBIs. TREX1 participates in the degradation of erythroblast DNA in the EBI and TREX1 D18N mice exhibit a normocytic normochromic anaemia.     

Providing HIV care for tuberculosis patients in sub-Saharan Africa.

Human immunodeficiency virus (HIV)/acquired immunedeficiency syndrome (AIDS) and tuberculosis (TB) cause an immense burden of disease in sub-Saharan Africa. A large amount of knowledge has been gathered in the last 15 years about the negative impact that HIV has on TB control, both at a programme level and at the level of the individual patient. Equally, interventions that are known to benefit patients have been tested and piloted, and these form important components of international TB-HIV guidelines, a TB-HIV strategic framework and an interim policy on TB-HIV coordination. Unfortunately, in sub-Saharan Africa there is little evidence that these interventions are being implemented on the ground, and one of the reasons for this paralysis is that the operational details are not well developed. This paper takes the three important HIV interventions of HIV testing and counselling, cotrimoxazole preventive treatment and antiretroviral treatment, and discusses some of the practical details of on-the-ground implementation. We hope that this will generate discussion, but above all, the impetus to start delivering services to patients.