Vitamin D deficiency in Malawian adults with pulmonary tuberculosis: risk factors and treatment outcomes.

SETTING: Vitamin D deficiency is common in African adults with tuberculosis (TB), and may be exacerbated by the metabolic effects of anti-tuberculosis drugs and antiretroviral therapy (ART). It is unclear whether vitamin D deficiency influences response to anti-tuberculosis treatment. OBJECTIVES: To describe risk factors for baseline vitamin D deficiency in Malawian adults with pulmonary TB, assess the relationship between serum 25-hydroxy vitamin D (25[OH]D) concentration and treatment response, and evaluate whether the administration of anti-tuberculosis drugs and ART is deleterious to vitamin D status during treatment. DESIGN: A prospective longitudinal cohort study. RESULTS: The median baseline 25(OH)D concentration of the 169 patients (58% human immunodeficiency virus [HIV] infected) recruited was 57 nmol/l; 47 (28%) had vitamin D deficiency (<50 nmol/l). Baseline 25(OH)D concentrations were lower during the cold season (P < 0.001), with food insecurity (P = 0.034) or in patients who consumed alcohol (P = 0.019). No relationship between vitamin D status and anti-tuberculosis treatment response was found. 25(OH)D concentrations increased during anti-tuberculosis treatment, irrespective of HIV status or use of ART. CONCLUSIONS: Vitamin D deficiency is common among TB patients in Malawi, but this does not influence treatment response. Adverse metabolic effects of drug treatment may be compensated by the positive impact of clinical recovery preventing exacerbation of vitamin D deficiency during anti-tuberculosis treatment.

Markers to differentiate between Kaposi's sarcoma and tuberculous pleural effusions in HIV-positive patients.

BACKGROUND: Kaposi's sarcoma (KS) and tuberculosis (TB) commonly cause pleural effusions in high human immunodeficiency virus (HIV) burden resource-limited countries. Differentiating between them is challenging, as pleural biopsy and TB culture are rarely available. OBJECTIVES: To identify markers to differentiate between TB effusions and KS effusions in HIV-positive patients, and to compare liquid culture and Xpert MTB/RIF in pleural fluid. METHODS: Fifty HIV-positive patients with pleural effusions recruited in Malawi underwent pleural ultrasound and aspiration. Fluid visual inspection, cell count, bacterial culture, glucose/protein, solid and liquid TB culture and Xpert were performed. RESULTS: The mean age of the patients was 32 years; 30/50 (60%) were male and 29 (58%) had cutaneous/oral KS. Thirteen (26%) pleural fluid samples were liquid culture-positive for TB, while 9/13 (69%) were Xpert-positive. Three (10.3%) KS patients had culture-positive TB effusions; 17 (58.6%) had KS effusions. The relative risk of TB in KS patients increased with limited KS, loculated fluid and low glucose. Eleven (52.3%) non-KS patients had culture-positive TB effusions associated with male sex, straw-coloured fluid and fibrin stranding on ultrasound. CONCLUSIONS: KS patients were most likely to have KS effusion, but TB should be considered. Most non-KS patients had TB, supporting the use of World Health Organization guidelines. Xpert identified two thirds of liquid culture-positive results.

Validation of the haemoglobin colour scale for screening blood donors in Malawi.

BACKGROUND: In 2009 Malawi introduced a new protocol to screen potential blood donors for anaemia, using the WHO Haemoglobin Colour Scale (HCS) for initial screening. Published studies of the accuracy of the HCS to screen potential blood donors show varying levels of accuracy and opinion varies whether this is an appropriate screening test. The aim of the study was to assess the validity of the HCS, as a screening test, by comparison to HemoCue in potential blood donors in Malawi. STUDY DESIGN AND METHODS: This was a blinded prospective study in potential blood donors aged over 18 years, at Malawi Blood Transfusion Service in Blantyre, Malawi. Capillary blood samples were analysed using the HCS and HemoCue, independent of each other. The sensitivity and specificity of correctly identifying ineligible blood donors (Hb ≤ 12 g/dL) were calculated. RESULTS: From 242 participants 234 (96.7%) were correctly allocated and 8 (3.3%), were wrongly allocated on the basis of the Haemoglobin Colour Scale (HCS) compared to HemoCue, all were subjects that were wrongly accepted as donors when their haemoglobin results were ≤ 12.0 g/dL. This gave a sensitivity of 100% and specificity of 96.7% to detect donor eligibilty. The negative predictive value of the HCS was 100% but the positive predictive value to identify ineligible donors on the basis of anaemia was only 20%. CONCLUSIONS: Initial screening with the HCS correctly predicts eligibility for blood donation in the majority of potential blood donors at considerable cost saving compared with use of HemoCue as the first line anaemia screening test, however, by this method a small number of anaemic patients were allowed to donate blood.

High prevalence in Malawi of sight-threatening retinopathy and visual impairment caused by diabetes: identification of population-specific targets for intervention.

AIMS: To report the prevalence of all grades of diabetic retinopathy and associations with demographic, clinical and biochemical variables in people with diabetes in Southern Malawi. METHODS: We report baseline data from a 24-month prospective cohort study. Subjects were systematically sampled from two hospital-based, primary care diabetes clinics. Visual acuity, glycaemic control, systolic blood pressure, HIV status, urine albumin-creatinine ratio, and haemoglobin and serum lipid levels were assessed. Retinopathy was graded at an accredited reading centre using modified Wisconsin grading of four-field mydriatic photographs. RESULTS: A total of 357 subjects were studied. Of these, 13.4% subjects were HIV-positive and 15.1% had anaemia. The overall prevalence rates of any retinopathy, sight-threatening diabetic retinopathy and proliferative retinopathy were 50.1% (95% CI 44.9-55.3), 29.4% (95% CI 24.7-34.1) and 7.3% (95% CI 4.6-10.0), respectively. In multivariate logistic analysis the presence of sight-threatening retinopathy was associated with duration of diabetes (odds ratio 1.11, 95% CI 1.05-1.17), HbA1c (odds ratio 1.31, 95% CI 1.13-1.50), systolic blood pressure (odds ratio 1.03, 95% CI 1.01-1.04), haemoglobin (odds ratio 0.98, 95% CI 0.96-0.99) and LDL cholesterol (odds ratio 1.63, 95% CI 1.18-2.25). No significant association with HIV status was observed. In all, 3.6 and 1.4% of people in our study cohort had visual acuity worse than 6/18 and 6/60 in the better eye, respectively. CONCLUSIONS: The present study found a prevalence of sight-threatening retinopathy in diabetes clinics in one Sub-Saharan African country of approximately four times that reported in recent European studies and a prevalence of proliferative retinopathy approximately 10 times higher. The association of sight-threatening retinopathy with lower haemoglobin level is a new finding. Our results highlight the urgent need for provision of services for retinopathy detection and management to avoid a large burden of vision loss.

Small alveolar macrophages are infected preferentially by HIV and exhibit impaired phagocytic function.

HIV-1-infected persons are at higher risk of lower respiratory tract infections than HIV-1-uninfected individuals. This suggests strongly that HIV-infected persons have specific impairment of pulmonary immune responses, but current understanding of how HIV alters pulmonary immunity is incomplete. Alveolar macrophages (AMs), comprising small and large macrophages, are major effectors of innate immunity in the lung. We postulated that HIV-1 impairs pulmonary innate immunity through impairment of AM physiological functions. AMs were obtained by bronchoalveolar lavage from healthy, asymptomatic, antiretroviral therapy-naive HIV-1-infected and HIV-1-uninfected adults. We used novel assays to detect in vivo HIV-infected AMs and to assess AM functions based on the HIV infection status of individual cells. We show that HIV has differential effects on key AM physiological functions, whereby small AMs are infected preferentially by the virus, resulting in selective impairment of phagocytic function. In contrast, HIV has a more generalized effect on AM proteolysis, which does not require direct viral infection. These findings provide new insights into how HIV alters pulmonary innate immunity and the phenotype of AMs that harbors the virus. They underscore the need to clear this HIV reservoir to improve pulmonary immunity and reduce the high incidence of lower respiratory tract infections in HIV-1-infected individuals.

Falls and other geriatric syndromes in Blantyre, Malawi: a community survey of older adults.

BACKGROUND: The prevalence of geriatric syndromes (falls, immobility, intellectual or memory impairment, and incontinence) is unknown in many resource-poor countries. With an aging population such knowledge is essential to develop national policies on the health and social needs of older people. The aim of this study was to provide a preliminary survey to explore the prevalence of falls and other geriatric syndromes and their association with known risk factors in people aged > 60 years in urban Blantyre, Malawi. METHODS: This was a cross-sectional, community survey of adults aged > 60 years. Subjects were recruited at home or in the waiting areas of chronic care clinics. They were interviewed to complete a questionnaire on age-associated syndromes and comorbid problems. The Abbreviated Mental Test (AMT) and Timed Up and Go (TUG) tests were carried out. RESULTS: Ninety-eight subjects were studied; 41% reported falling in the past 12 months, 33% of whom (13% of all subjects) were recurrent fallers. Twenty-five percent reported urine incontinence, 66% self-reported memory difficulties, and 11% had an AMT score < 7. A history of falling was significantly associated with urine incontinence (p=0.01), self-reported memory problems (p=0.004) and AMT score < 7 (p=0.02). CONCLUSIONS: Geriatric syndromes, including falls, appear to be prevalent in older people in Blantyre, Malawi. Falling is associated with cognitive impairment and urinary incontinence. There is an urgent need for more understanding of geriatric problems in this setting to develop national policies on health and social needs of older people. It is likely that many of the contributory factors to falls would be amenable to multifactorial interventions similar to those found to be effective in developed countries.

HIV post-exposure prophylaxis programmes in the developed and developing world: can we learn from each other?

In an audit of HIV post-exposure prophylaxis (PEP) programmes in Blantyre, Malawi, and Liverpool, UK, a striking common deficiency was poor attendance of follow-up visits and of HIV testing to determine efficacy of PEP. Causes of poor follow-up after PEP need to be explored in both settings.

The prevalence of renal impairment among adults with early HIV disease in Blantyre, Malawi.

We determined the prevalence of renal impairment and possible HIV-associated nephropathy (HIVAN) in adults with World Health Organization (WHO) stages I or II HIV, presenting to the antiretroviral therapy (ART) clinic in a central hospital in Malawi. We enrolled 526 ART-naïve subjects, 67% women, median age 34 (17-73) years and mean CD4 count 305 (3-993) cells/µL. Blood pressure, weight, urine dipstick and microscopy, CD4 cell count and serum creatinine were measured. Creatinine clearance (CrCL) was estimated using the Cockcroft-Gault equation. Possible HIVAN was diagnosed based on levels of proteinuria and CrCl. In all, 23.3% had proteinuria (≥ 1+). 57.4% had reduced CrCl (< 90 mL/minute): 18.8% had moderate (CrCl 30-59 mL/minute) and 2.2% severe (CrCl <30 mL/minute) renal dysfunction. Extrapolating from renal biopsy studies that confirmed HIVAN, the proportion of patients with HIVAN in our clinic ranges from 1.8-21.2%. We conclude that renal impairment was common, though rarely severe, among HIV-infected adults with clinically non-advanced HIV disease. Renal dysfunction has been demonstrated to be a risk factor for (early) mortality. These results are relevant for ART programmes, such as those in Malawi, where renal function is not routinely assessed.

Prevalence of vitamin D deficiency in adult tuberculosis patients at a central hospital in Malawi.

Vitamin D deficiency (VDD) is associated with impaired mycobacterial immunity and susceptibility to tuberculosis (TB). We measured 25 hydroxy vitamin D levels in 161 adult TB patients at a central hospital in Malawi, of whom 120 (74.5%) had ≤75 nmol/l (hypovitaminosis D), 68 (42%) had ≤50 nmol/l (VDD) and 13.6% of in-patients and 6.8% of out-patients had ≤25 nmol/l (severe VDD). In-patients had lower body mass index (BMI; 19.0 vs. 20.5, P < 0.004), and vitamin D levels were lower in those with BMI < 20. However, on multiple regression analysis in-patient status and BMI were not associated with vitamin D level. We conclude that VDD is common in adult TB patients in Malawi. In this small sample, it was not possible to identify any independent associations of VDD.

The implications of a growing evidence base for drug use in elderly patients. Part 4. Vitamin D and bisphosphonates for fractures and osteoporosis.

Fractures are common in elderly subjects, disabling and occasionally fatal. Their incidence increases exponentially with age, with the commonest affected sites being the wrist, vertebrae, hip and humerus. Of these, hip fractures are the most relevant in terms of morbidity and financial cost. The increase in fracture rate with age is believed to result predominantly from age-related increases in the incidence of osteoporosis and falls. This article reviews the evidence for the use of vitamin D and bisphosphonates for the prevention of bone fractures and osteoporosis in elderly patients.

Amelanotic malignant melanoma disguised as a diabetic foot ulcer.

UNLABELLED: BACKGROUND/CASE REPORT A female patient with diet-controlled Type 2 diabetes mellitus, presented with disseminated malignancy. She had a 15-year history of a diabetic foot ulcer, which was subsequently found to be an amelanotic malignant melanoma. She had recently received immunosuppressive treatment for an episode of nephrotic syndrome secondary to focal segmental glomerulosclerosis. CONCLUSIONS: This case raises two important points. Firstly, whether non-healing diabetic foot ulcers should be biopsied, and secondly, whether the spread of the malignant melanoma was precipitated by immunosuppressive treatment.

Neuromuscular and psychomotor function in elderly subjects who fall and the relationship with vitamin D status.

Vitamin D and calcium supplementation significantly reduces the incidence of fractures. Evidence suggests vitamin D deficiency impairs neuromuscular function, causing an increase in falls and thereby fractures. The relationship between vitamin D, functional performance, and psychomotor function in elderly people who fall was examined in a prospective cross-sectional study. Patients were recruited from a falls clinic and stratified according to serum 25-hydroxyvitamin-D levels (25OHD): group 1, 25OHD < 12 microg/liter; group 2 25OHD, 12-17 microg/liter; and group 3, 25OHD > 17 microg/liter. Healthy elderly volunteers with 25OHD > 17 microg/liter comprised group 4 (n = 20/group). Measures included aggregate functional performance time (AFPT, seconds), isometric quadriceps strength (Newtons), postural sway (degrees), and choice reaction time (CRT, seconds). Serum bone biochemistry, 25OHD, and parathyroid hormone levels were measured. Patients who fell had significantly impaired functional performance, psychomotor function, and quadriceps strength compared with healthy subjects (AFPT: 51.0 s vs. 32.8 s,p < 0.05; CRT: 1.66 s vs. 0.98 s,p < 0.05; strength: 223N vs. 271N, t = 2.35, p = 0.02). Group 1 had significantly slower AFPT (66.0 s vs. 44.8 s, t = 4.15, p < 0.05) and CRT (2.37 s vs. 0.98 s, t = 3.59, p < 0.05) than groups 2 and 3. Group 1 had the greatest degree of postural sway and the weakest quadriceps strength, although this did not reach significance. Multivariate analysis revealed 25OHD as an independent variable for AFPT, CRT, and postural sway. PTH was an independent variable for muscle strength. Older people who fall have impaired functional performance, psychomotor function, and muscle strength. Within this group, those with 25OHD < 12 microg/liter are the most significantly affected.

Urinary iodine concentrations and thyroid function in adult Zimbabweans during a period of transition in iodine status.

BACKGROUND: In 1993 the compulsory iodization of salt was introduced in Zimbabwe, a country that was previously an area of severe iodine deficiency. OBJECTIVE: The objective of this study was to document urinary iodine excretion and biochemical thyroid function in seemingly healthy, community-dwelling adults after the introduction of iodization. DESIGN: A multistage, random sampling method was used in rural and urban settings to identify households from which the senior household member (aged >35 y) was recruited (alternating male and female recruits). Demographic data were collected for each subject and urinary and venous blood samples were taken. Urinary iodine excretion and serum thyroid hormone status (thyrotropin and total thyroxin) were evaluated according to age, sex, and area of residence. RESULTS: A total of 736 adults were recruited (253 men; mean age: 64 y). Urinary iodine concentrations were high [median (first and third quartiles): 4.41 (2.84, 6.78) micromol/L, or 560 (360, 860) microgram/L] and were significantly higher in rural areas than in urban areas [4.73 (3.07, 7.14) micromol/L, or 600 (390, 906) microgram/L, compared with 3.47 (2.05, 4.73) micromol/L, or 440 (260, 600) microgram/L; P < 0.001]. Urinary iodine excretion declined significantly with increasing age (r = -0.29, P < 0.001). Serum thyroid status suggested that the prevalence of biochemical hyperthyroidism in the study was 3%, with 13 of 415 cases in rural and 3 of 149 cases in urban subjects. CONCLUSION: This study reaffirms the need to continuously monitor iodine replacement programs to ensure efficacy.

Morbidity and disability in elderly Zimbabweans.

BACKGROUND: the population aged over 60 years in Zimbabwe is expanding. Despite the likely increased demand on medical services that this will bring, little is known about the health needs of this elderly population. OBJECTIVE: to record the prevalence of disability (impairment of activities of daily living), subjective morbidity (symptoms), the social circumstances and the utilization of health services in a group of elderly Zimbabweans. DESIGN: cross-sectional community survey. SETTING: a remote rural area in North Eastern Zimbabwe and two urban townships located approximately 80 km from Harare. SUBJECTS: 278 subjects (154 women, 174 rural), aged > 60 years (range 60-92) living at home. METHOD: subjects were selected by random cluster sampling. They were assessed in a structured interview and underwent physical examination including visual acuity, inspection for cataracts and assessment of mobility. RESULTS: less than 4% experienced difficulty with self-maintenance activities of daily living, but 30% had difficulty with instrumental activities. The former were all visually impaired and both visual and mobility problems contributed to the latter. Elderly people experienced many symptoms but had inadequate access to health services and used medication infrequently. Subjects were mainly self-sufficient for financial income and 60% still worked. They had declining resources with age and received little help from the social welfare department. Their health and functional abilities deteriorated with age but it was older subjects who had most difficulty getting to the clinic. Simple measures such as cataract surgery and analgesics were available only to the minority or not at all. CONCLUSIONS: this study highlights problem areas where simple, low-cost measures could make a difference to the morbidity and disability of elderly Zimbabweans.

Changes in growth hormone, insulin, insulinlike growth factors (IGFs), and IGF-binding protein-1 in chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is characterized by severe physical and mental fatigue of central origin. Similar clinical features may occur in disorders of the hypothalamopituitary axis. The aim of the study was to determine whether patients with CFS have abnormalities of the growth hormone/insulinlike growth factor (GH-IGF) axis basally or following hypothalamic stimulation with insulin-induced hypoglycemia. We compared levels of GH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), insulin, and C-peptide in nondepressed CFS patients and normal controls. We found attenuated basal levels of IGF-I (214 +/- 17 vs. 263.4 +/- 13.4 micrograms/L, p = .036) and IGF-II (420 +/- 19.8 vs. 536 +/- 24.3 micrograms/L, p = .02) in CFS patients and a reduced GH response to hypoglycemia (peak GH; 41.9 +/- 11.5 vs. 106.0 +/- 25.6 mU/L, p = .017). Insulin levels were higher (7.6 +/- 1.0 vs. 4.3 +/- 0.8 mU/L, p = .02) and IGFBP-1 levels were lower (19.7 +/- 4.6 vs. 43.2 +/- 2.7 mg/L, p = .004) in CFS patients compared with controls. This study provides preliminary data abnormalities of the GH-IGF axis in CFS. It is not apparent whether these changes are components of a primary pathological process or are acquired secondary to behavioral aspects of CFS such as reduced physical activity.

Anaemia, macrocytosis, vitamin B12 and folate levels in elderly Zimbabweans.

OBJECTIVES: To establish the ranges of full blood count (FBC), vitamin B12 and folate levels and to determine the prevalence of occult haematological abnormalities in older Zimbabweans. STUDY DESIGN: Community based cross sectional survey. SUBJECTS: 278 randomly selected healthy Zimbabweans aged > 65 years. INTERVENTIONS/STUDY FACTORS: Haemoglobin level, MCV, folate, B12 alcohol consumption. RESULTS: The median Hb was males 14.0 (range 8 to 18.3), females 13.1 g/dl (7.9 to 18.1). 23% were anaemic (Hb < 13 g/dl in males, < 12 g/dl in females), 3% with microcytic and 20% with macrocytic indices. Overall 13% had low vitamin B12 and 30% had low folate levels. Folate levels were significantly lower in urban subjects and B12 levels were significantly lower in rural subjects. Fifty four subjects (21%) had an MCV > 100 fl. In this group, low folate levels were found in 22, low B12 levels in nine, excessive alcohol in eight and two subjects had elevated TSH. The MCV was higher in urban subjects. CONCLUSIONS: This study has revealed a large amount of occult haematological abnormality and interesting differences between rural and urban subjects. It focuses attention on low levels of folate, which should be preventable by simple nutritional education, as an extensive problem in the community.