The profile of risk factors and in-patient outcomes of stroke in Kumasi, Ghana.

BACKGROUND: Stroke is an emerging public health challenge in Ghana requiring urgent attention for its control. Because some of the risk factors for stroke are modifiable, characterisation of these risk factors in the Ghanaian population as well as outcomes of stroke are urgently needed to guide policy for non-communicable diseases. We therefore conducted this study to evaluate the frequencies of the traditional risk factors and outcomes of stroke at the main tertiary referral centre in the middle belt of Ghana in a prospective observational study. METHODS AND RESULTS: Patients with a clinical diagnosis of stroke were consecutively recruited and vascular risk factors were assessed as well as markers of severity of stroke and in-patient treatment outcomes. 265 patients were recruited, 56.6% were females and mean ± SD age of 64.6 ± 14.54 years. 85%, 73% and 58% of patients had systemic arterial hypertension, physical inactivity and obesity respectively as common risk factors. We identified that patients with stroke had a median of 3 traditional risk factors, were unaware of the presence of these risk factors or were poorly controlled if known. Stroke was associated with a high in-patient case fatality rate of 43% principally among patients with haemorrhagic stroke. CONCLUSIONS: Our findings indicate that urgent concerted efforts are required to improve public awareness and management of the prevailing risk factors of stroke in Ghana.

Circulating adiponectin is associated with renal function independent of age and serum lipids in west africans.

Adiponectin, a protein secreted by adipose tissue, has been associated with renal dysfunction. However, these observations have not been adequately investigated in large epidemiological studies of healthy individuals in general and in African populations in particular. Hence, we designed this study to evaluate the relationship between adiponectin and renal function in a large group of nondiabetic West Africans. Total adiponectin was measured in 792 participants. MDRD and Cockroft-Gault (CG-) estimated GFR were used as indices of renal function. Linear and logistic regression models were used to determine the relationship between adiponectin and renal function. Adiponectin showed an inverse relationship with eGFR in univariate (Beta(MDRD) = -0.18, Beta(CG) = -0.26) and multivariate (Beta(MDRD) = -0.10, Beta(CG) = -0.09) regression analyses. The multivariate models that included age, sex, BMI, hypertension, smoking, HDL-C, LDL-C, triglycerides, and adiponectin explained 30% and 55.6% of the variance in GFR estimated by MDRD and CG methods, respectively. Adiponectin was also a strong predictor of moderate chronic kidney disease (defined as eGFR < 60 mL/min/1.73 m(2)). We demonstrate that adiponectin is associated with renal function in nondiabetic West Africans. The observed relationship is independent of age and serum lipids. Our findings suggest that adiponectin may have clinical utility as a biomarker of renal function.

Agouti-related protein promoter variant associated with leanness and decreased risk for diabetes in West Africans.

OBJECTIVE: The role of the central melanocortin system in the development of obesity has been extensively studied. Single-nucleotide polymorphisms (SNPs) within several candidate genes have been associated with food intake and obesity-related phenotypes; however, few of these associations have been replicated. SNPs in the agouti-related protein (AGRP) gene coding (Ala67Thr, 199G/A) and promoter (-38C/T) have been reported to be associated with body mass index (BMI), fat mass (FM) and percent body fat, in populations of European and African descent. In this study, we evaluated the association between the functional AGRP -38C/T promoter SNP and weight-related traits, namely BMI, FM and fat-free mass (FFM), as well as diabetes status. DESIGN: An association study of the AGRP -38C/T SNP and indices of obesity and diabetes status. SUBJECTS: A well-characterized population of 538 West Africans from Ghana and Nigeria recruited in the AADM (Africa America Diabetes Mellitus) study (mean age 52 years, 41.3% males, 71% diabetic). MEASUREMENTS: Genotyping of the AGRP -38C/T SNP, BMI, FM, FFM and fasting plasma glucose. RESULTS: Women carrying two copies of the variant T allele had significantly lower BMI (OR=0.47; 95% CI, 0.25-0.87). Also, men with at least one copy of the variant T allele were over two times less likely to be diabetic than other men (OR=0.44; 95% CI, 0.22-0.89). CONCLUSION: Our results replicate previous findings and implicate the AGRP -38C/T SNP in the regulation of body weight in West Africans.

A genome-wide scan for quantitative trait loci linked to obesity phenotypes among West Africans.

OBJECTIVE: To identify quantitative trait loci (QTL) for three obesity phenotypes: body mass index (BMI), fat mass (FM) and percent body fat (PBF) in West Africans with type 2 diabetes (T2DM). DESIGN: An affected sibling pair (ASP) design, in which both siblings had T2DM. Obesity was analyzed as a quantitative trait using a variance components approach. SUBJECTS: Sib-pairs affected with T2DM from the Africa America Diabetes Mellitus (AADM) study, comprising 321 sibling pairs and 36 half-sibling pairs. MEASUREMENTS: Weight was measured on an electronic scale to the nearest 0.1 kg, and height was measured with a stadiometer to the nearest 0.1 cm. Body composition was estimated using bioelectric impedance analysis (BIA). Genotyping was carried out at the Center for Inherited Disease Research (CIDR) with a panel of 390 trinucleotide and tetranucleotide repeats. RESULTS: The obesity-related phenotype showing the strongest linkage evidence was PBF on chromosome 2 (LOD 3.30 at 72.6 cM, marker D2S739). Suggestive linkage to FM was found on chromosomes 2 (LOD 2.56 at 80.4 cM) and 5 (LOD 2.25 at 98 cM, marker D5S1725). The highest LOD score for BMI was 1.68 (chromosome 4, 113.8 cM). The areas of linkage for the three phenotypes showed some clustering as all three phenotypes were linked to the same regions of 2p13 and 5q14, and our study replicated linkage evidence for several regions previously reported in other studies. CONCLUSION: We obtained evidence for several QTLs on chromosome 2, 4 and 5 to three obesity phenotypes. This study provides data on the genetics of obesity in populations that are currently under represented in the global effort directed at understanding the pathophysiology of excess adiposity in free living individuals.

Skin diseases in Ghana and the UK.

BACKGROUND: Although diseases of the skin have been studied in some African countries, the provision of dermatology services is as yet a relatively underdeveloped aspect of medicine in sub-Saharan Africa. OBJECTIVE: To determine the pattern of skin diseases seen in a sub-Saharan community and to compare it with that seen in a European community. METHODS: The diagnoses of the principal presenting complaint of 2254 consecutive new patients seen at the dermatology clinic of Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana, are presented and compared with those of 3383 consecutive new patients seen at the dermatology clinic of The William Harvey Hospital (WHH), Ashford, Kent, UK. RESULTS: The most common conditions in Ghana were infections (46.3%; UK, 12%). In the UK, the most common conditions were malignant and premalignant diseases of the skin (22.2%; Ghana, 0.5%) and benign tumors (16.8%; Ghana, 0.5%). Dermatitis was common in both countries (Ghana, 18.4%; UK, 16.0%). Psoriasis was more common in the UK (6.2%) than in Ghana (0.4%). In Ghana, fixed drug eruption, mainly due to cotrimoxazole (Septrin), was not rare (27 cases), and complications from cosmetic skin lightening creams were a frequent problem among women (86 cases). No cases of rosacea were found in Ghana, but it was not uncommon in the UK (1.6%). CONCLUSIONS: The patterns of skin diseases are different in the two countries. It is hoped that this study may help to catalyze the further development of dermatology services in Ghana.

In search of susceptibility genes for type 2 diabetes in West Africa: the design and results of the first phase of the AADM study.

PURPOSE: The purpose of this study is to map type 2 diabetes susceptibility genes in West African ancestral populations of African-Americans, through an international collaboration between West African and US investigators. DESIGN AND METHODS: Affected sib-pairs (ASP) along with unaffected spouse controls are being enrolled and examined in West Africa, with two sites established in Ghana (Accra and Kumasi) and three in Nigeria (Enugu, Ibadan, and Lagos). Eligible participants are invited to study clinics to obtain detailed epidemiologic, family, and medical history information. Blood samples are drawn from each participant to measure glucose, insulin, C-peptide, total cholesterol, LDL, HDL, triglycerides, albumin, creatinine, urea, uric acid, total calcium and to detect autoantibodies to glutamic acid decarboxylase (GAD). DNA is isolated from frozen white blood cells obtained from 20 ml of EDTA whole blood samples. RESULTS: With full informed consent, 162 individuals from 78 families have been enrolled and examined since the Africa America Diabetes Mellitus (AADM) study began in June of 1997. Logistics of field examinations and specimen shipping have been successfully established. At the end of the third year of field activity (September 2000) the AADM study will have enrolled and performed comprehensive examination on 400 ASP with type 2 diabetes, for a minimum of 800 cases and 200 controls from Ghana and Nigeria. At the current participation rate, the goal of 400 sib-pairs and 200 controls will be met before the scheduled closing date. CONCLUSIONS: The AADM study will create a comprehensive epidemiologic and genetic resource that will facilitate a powerful genome-wide search for West African susceptibility genes to type 2 diabetes.

Screening for viral markers in volunteer and replacement blood donors in West Africa.

BACKGROUND AND OBJECTIVES: West Africa is a highly endemic area for viral infections. The prevalence of five viral markers was determined in Ghanaian blood donors. MATERIALS AND METHODS: Replacement and volunteer blood donors were screened using enzyme immunoassays (EIAs) for hepatitis B surface antigen (HBsAg), human immunodeficiency virus antibodies (anti-HIV), HIV p24 antigen, human T-cell lymphocytotrophic virus-I and -II antibodies (anti-HTLV-I/II) and hepatitis C virus antibodies (anti-HCV). RESULTS: HBsAg was present at an equally high frequency (15%) in young volunteer (median age 18 years) and older replacement (median age 33 years) blood donors. In contrast, the prevalence of anti-HIV and anti-HCV was significantly higher in replacement blood donors (2.4 and 0.3%, respectively, P < 0.001). HCV RNA was detected in 74 or 55% of seropositive donors, depending on the confirmatory criteria used. No p24 antigen-positive/anti-HIV-negative donations were found. The prevalence of HTLV-I/II was generally low (0.5%). CONCLUSION: All blood donations should be screened for hepatitis B virus (HBV), HIV and HCV markers.

Pulmonary tuberculosis in Kumasi, Ghana: presentation, drug resistance, molecular epidemiology and outcome of treatment.

To assist implementation of tuberculosis (TB) control measures, knowledge of the disease characteristics in a community is essential. This study in Kumasi, Ghana, correlates the clinical presentation, microbiology, molecular epidemiology and clinical outcome of thirty consecutively diagnosed patients with new smear-positive pulmonary TB. Several important factors that potentially promote disease transmission in the community were identified: patients had prolonged duration of productive cough prior to diagnosis (mean=4.1 months; SD=2.1); the disease was typically advanced at presentation and Ziehl-Neelson sputum smears indicated a high bacterial load (80% graded > AFB++); home accommodation was overcrowded with a mean of 3.3 other persons sleeping in the same room as the patients at night. IS6110 restriction fragment length polymorphism (RFLP) fingerprinting of 25 isolated (23 Mycobacterium tuberculosis and 2 Mycobacterium africanum) from epidemiologically unrelated cases identified 3 identical strains and 3 clusters containing 2, 4 and 8 isolates of > or =80% similarity, suggesting high rates of disease transmission. A high prevalence of primary resistance to isoniazid was found (6 out 26; 23%) but resistance to rifampicin, pyrazinamide, ethambutol, streptomycin and ciprofloxacin was not detected. Smear coversion at 2 months and final outcome of treatment with short courses chemotherapy were independent of isoniazid resistance, but the rate of treatment default was unacceptably high (37%). High rates of disease transmission, primary isoniazid resistance and treatment default all indicate poor TB control. The use of rifampicin-containing short-course chemotherapy in this community must be accompanied by adequate resources and infrastructure to ensure very stringent treatment supervision to improve case-holding and reduce the risk of multi-drug resistance.

A national diabetes care and education programme: the Ghana model.

An account is given of how a national diabetes care and education programme was developed in Ghana, a developing country, through international collaboration of medical schools, industry and government health care institutions. The approach is by way of trained diabetes teams consisting of physicians, dietitians and nurse educators at two tertiary institutional levels (teaching hospitals) who in turn trained teams consisting of physicians, dietitians or diettherapy nurses, nurse educators and pharmacists at regional and district/sub-regional levels to offer care and education to patients and the community. In three years all regional and about 63% of sub-regional/district health facilities had trained diabetes health care teams, run diabetes services and had diabetes registers at these institutions. Additionally a set of guidelines for diabetes care and education was produced. All programme objectives with the exception of one (deployment of diabetes kits) were met. Distances to be travelled by persons with diabetes to receive diabetes care had been reduced considerably. The success of the project has given an impetus to the collaborators to extend the programme to the primary health care level. The continuing prohibitive prices of diabetes medications and supplies however, could be addressed by removing taxes on such supplies. The Ghana diabetes care model, a 'top-down' approach, initially involving two diabetes centres is recommended to other developing countries, which intend to incorporate diabetes care and education into their health care system.

Elevated serum concentrations of soluble CD14 in HIV- and HIV+ patients with tuberculosis in Africa: prolonged elevation during anti-tuberculosis treatment.

Data are limited regarding serum concentrations of soluble CD14 (sCD14), a marker of macrophage activation, in patients with active tuberculosis (TB) and during drug treatment. In this study, concentrations of sCD14 were measured in serum samples obtained from 105 African subjects who were categorized into one of four groups: persons with pulmonary TB alone (TB+HIV-, n = 30), pulmonary TB and HIV co-infection (TB+HIV+, n = 20), or HIV infection alone (TB-HIV+, n = 25), and healthy controls (TB-HIV-, n = 30). Mean total sCD14 was significantly increased in serum of patients with newly diagnosed pulmonary TB (mean = 6.6 g/ml, s.d. = 1.6 g/ml) compared with healthy controls (mean = 3.1 g/ml, s.d. = 0.6 g/ml; P < 0.0001), and this elevation comprised proportionate increases in the alpha (2.1-fold greater, P < 0.0001) and beta (2.0-fold greater, P < 0. 0001) forms of sCD14. Total sCD14 was also increased in serum of HIV-infected patients (mean = 4.1 g/ml, s.d. = 1.9 g/ml; P < 0.01), but the highest concentrations were observed in patients with pulmonary TB and HIV co-infection (mean = 8.7 g/ml, s.d. = 3.1 g/ml; P < 0.0001). Analysis of serum samples prospectively collected from TB+HIV-patients during the first 3 months of successful anti-TB treatment demonstrated steep reductions in mean concentrations of the acute-phase protein, C-reactive protein, and the soluble lymphocyte activation marker, sCD25. In contrast, levels of sCD14 increased during the first month of treatment and slowly declined thereafter. These data indicate that the serum concentration of sCD14 is not a sensitive index of response to anti-TB treatment and suggest that cellular activation resolves more slowly in the macrophage pool compared with the lymphocyte pool during anti-TB treatment.

Resolution of the acute-phase response in West African patients receiving treatment for pulmonary tuberculosis.

SETTING: The Komfo Anokye Teaching Hospital, Kumasi, Ghana, West Africa. OBJECTIVE: To evaluate simple and commonly used parameters of the acute-phase response as correlates of successful resolution of smear-positive pulmonary tuberculosis (PTB) during drug treatment. DESIGN: Serum C-reactive protein (CRP) concentration, erythrocyte sedimentation rate (ESR), body weight, and blood haemoglobin were measured in human immunodeficiency virus (HIV) negative Ghanaian patients with PTB (n = 15) and in age- and sex-matched healthy controls (n = 15). These parameters were subsequently measured in patients after 1, 2 and 3 months of antituberculosis treatment. Serum concentrations of soluble interleukin-2-receptor-alpha (sCD25) were also measured as a comparative index of resolution of the systemic inflammatory process. RESULTS: Anti-tuberculosis treatment resulted in sputum smear conversion in all 15 patients. After one month of treatment, reductions in serum CRP concentration (>20%) and increases in haemoglobin concentration (>0.4 g/dl) occurred in the majority of patients and correlated with steep reductions in serum levels of sCD25. In contrast, weight loss and elevated ESR were slower to resolve, and were insensitive early markers of response to treatment. CONCLUSION: A fall in serum CRP and a rise in blood haemoglobin are correlates of the initial response to drug treatment of PTB. These parameters may assist in the evaluation of empiric trials of treatment in microbiologically unconfirmed cases of suspected PTB.

Sustained plasma TNF-alpha and HIV-1 load despite resolution of other parameters of immune activation during treatment of tuberculosis in Africans.

OBJECTIVE: To determine the impact of treatment of tuberculosis on plasma HIV-1 load in African subjects and to correlate viral load with response to treatment and changes in immune activation. DESIGN: Clinical and microbiological responses, immune activation parameters and plasma HIV-1 load were determined in 20 patients with pulmonary tuberculosis and HIV-1 coinfection in Ghana, West Africa during the first 3 months of anti-tuberculosis treatment. METHODS: Plasma HIV-1 load and markers of immune activation were determined by commercially available assays. Human leukocyte antigen (HLA)-DR incorporation into the HIV-1 envelope was measured by using an immunomagnetic capture technique. RESULTS: Treatment of tuberculosis resulted in significant improvements in weight and haemoglobin, a high sputum smear conversion rate and marked reductions in mean plasma tumour necrosis factor (TNF) receptor-1, interleukin-6 and C-reactive protein. Furthermore, incorporation of host HLA-DR into the HIV-1 envelope decreased; this also suggested a reduction in immune activation of the cells supporting viral replication. However, of importance with regard to AIDS pathogenesis, neither mean plasma TNF-alpha nor HIV-1 load decreased significantly. CONCLUSIONS: The failure of HIV-1 plasma load to decline significantly during the initial months of anti-tuberculosis treatment is associated with high, sustained systemic levels of TNF-alpha. The dissociation between the sustained levels of plasma TNF-alpha and the major reductions in other, diverse immune activation parameters may represent dysregulation of cytokine production in these African patients.

Pulmonary tuberculosis: radiological features in west Africans coinfected with HIV.

A retrospective study was performed to document and compare the radiological appearances of newly diagnosed pulmonary tuberculosis (PTB) in groups of West African patients with (n = 86) and without (n = 106) human immunodeficiency virus (HIV) coinfection. Analysis of chest radiographs showed that the HIV-positive group had less consolidation (mean 3.1 zones vs 3.7 zones; p < 0.05), less apical involvement (64.0% vs 85.5%; p < 0.001), less bronchopulmonary spread (27.9% vs 58.5%; p < 0.001), less volume loss (53.5% vs 76.4%; p < 0.001) and less pleural thickening (46.5% vs 61.3%; p < 0.05) compared with the HIV-negative group. However, HIV-positive patients more commonly had pleural effusions (17.4% vs 6.6%; p < 0.05) and lymphadenopathy (9.3% vs 1.9%; p < 0.05). Previous studies on this subject from sub-Saharan Africa have focused either on selected patient groups likely to have more advanced immunosuppression or on smear-positive cases only, or where there has been only limited radiological documentation. This study suggests that the highly significant differences that exist may not be as frequent as previously shown. The lower frequencies of bronchopulmonary pattern of consolidation and pleural thickening in HIV-positive subjects have not previously been documented. The possible reasons for the altered radiographic appearance of PTB in HIV positive subjects are discussed.

Spoligotyping in molecular epidemiology of tuberculosis in Ghana.

OBJECTIVES: Molecular epidemiological studies of Mycobacterium tuberculosis in high prevalence areas in sub-Saharan Africa are hampered by the difficulty of culturing organisms from clinical samples. This study aimed to evaluate for application in a developing country, a modification of a novel polymerase chain reaction (PCR) based molecular epidemiological typing method, termed spoligotyping. METHODS: DNA extraction from sputum was followed by PCR amplification of spacers between direct repeats in the M. tuberculosis genome, and hybridization to a range of the 53 known spacer sequences. RESULTS: Sputum from 175 patients in the Ashanti region of Ghana were collected, and satisfactory spoligotyping results were obtained in 159. A total of 100 different spoligotype patterns were observed with 84 patients having unique patterns and the remainder falling into 16 clusters. A number of epidemiologically linked cases were shown to be unrelated on the basis of different spoligotype patterns, but epidemiological links were not found to explain clusters. Comparison of spoligotyping of DNA extracted from sputum with restriction fragment length polymorphism (RFLP) from mycobacterial culture in a subset of 25 patients, indicated that spoligotyping was less discriminatory than RFLP, Sixteen spoligotype patterns were shown to comprise 2 3 different RFLP patterns. CONCLUSIONS: This study suggests that the PCR based technique of spoligotyping can be applied successfully to DNA extracted from sputum collected in the setting of a developing country, but that this is less discriminatory than RFLP. Spoligotyping is particularly useful when used to support conventional epidemiology since a proportion of false epidemiological associations can be identified.

Hypertension and renal failure in Kumasi, Ghana.

Hypertension is common in West Africa and likely to become more common as urbanisation increases. There are at present few facilities for the detection and management of hypertension so the influence it has on overall morbidity and mortality in the population is not clear. The objectives of the study were to assess: (a) renal disease and blood pressure related admissions and deaths among acute medical admissions to Komfo Anokye Teaching Hospital, Kumasi, during an 8-month period; and (b) the burden of renal disease among out-patient hypertensives at the same hospital. Ward admission books were examined in the four acute medical wards to ascertain admission diagnosis and cause of death (two 4-month periods in 1995 and 1996). Clinical assessment (blood pressure, plasma creatinine, proteinuria) was also made of 448 consecutive out-patient hypertensives seen between March 1995 and April 1996. Five hundred and ninety-three (17.9%) of 3317 acute medical admissions were ascribable to a cardiovascular cause (hypertension, heart failure, stroke); 171 (28.8%) of these died. One hundred and sixty-six (5.0%) had renal disease of whom 45 (27.1%) died, usually of end-stage renal disease. Among the 448 hypertensive out-patients, 30.2% (110 out of 365) had a plasma creatinine >140 micromol/l (48 > or = 400 micromol/l) and 25.5% (96 out of 376) had proteinuria. Eighty-nine of the 448 had a diastolic blood pressure > or =115 mm Hg; in this group 38 (42.7%) had a plasma creatinine of >140 micromol/l (and 18 or 20.2% > or =400 micromol/l). In conclusion, cardiovascular and renal disease are important contributors to morbidity and mortality among acute medical admissions to a large city hospital in Ghana. Among out-patient hypertensives renal disease is an important complication, especially in those with the more severe hypertension.

Life-threatening cutaneous reactions to thiacetazone-containing antituberculosis treatment in Kumasi, Ghana.

Antituberculosis treatment containing thiacetazone is associated with a high incidence of life-threatening cutaneous drug reactions in patients infected with the human immunodeficiency virus (HIV). In order to develop a local policy concerning the use of this drug, a study was undertaken to determine the incidence of such reactions in a total of 1063 Ghanaian adult patients treated for pulmonary tuberculosis (PTB) with thiacetazone-containing regimens. The incidence was retrospectively determined in 3 different treatment groups, comparing: (A) unselected use of thiacetazone; (B) exclusion of thiacetazone from all patients with positive HIV serology; (C) selective exclusion of thiacetazone from patients with clinical criteria suggesting HIV infection plus education of health workers and patients. Of the 408 patients in group A receiving thiacetazone, 9 (2.2%) developed life-threatening cutaneous reactions and 7 of these were HIV-positive. Overall, 6.8% of HIV-positive patients compared to 0.65% of HIV-negative patients developed severe reactions (P < 0.01; relative risk = 10.5). Six of the 9 patients with reactions died. All 379 patients in group B were screened for HIV antibodies and positive cases (23%) received a regimen in which thiacetazone was substituted by ethambutol. In contrast to Group A, only one HIV-negative patient (0.26%) developed a severe cutaneous reaction (P = 0.02). Among 276 patients in group C, thiacetazone was substituted with ethambutol only in those with clinical evidence of HIV infection (8%) and staff and patients were educated about early recognition of the side-effect. With this policy, these were no admissions with severe cutaneous reactions compared to 2.2% of those in group A (P = 0.01). In conclusion, a policy of selective use of thiacetazone in the treatment of PTB based on clinical criteria combined with patient and staff education was found to be a practical and cost-effective strategy combating severe cutaneous reactions to thiacetazone.

Pulmonary tuberculosis in adults: factors associated with mortality at a Ghanaian teaching hospital.

Tuberculosis (TB) is a leading cause of global mortality. The aim of this study was to compare factors associated with poor outcome (death) and good outcome (cure) of adult patients receiving treatment for pulmonary TB (PTB) at the Komfo Anokye Teaching Hospital, Kumasi, Ghana. The case notes and chest radiographs of 80 such patients who died were retrospectively reviewed and compared to 80 patients who were cured during the same period. Patients who died were 3.4 times more likely to be HIV-positive (p < 0.001). Mortality was also associated with increased age (p < 0.001), residence in a rural area (p < 0.05) sputum smear-negative disease (p < 0.01), and more prolonged symptom duration prior to initial diagnosis (p < 0.05). Furthermore, patients who died were 2.1 times more likely to have a history of previous TB treatment (p < 0.01), 2.0 times more likely to have previously defaulted from treatment ((p < 0.05), and 2.9 times more likely to have > or = 5 chest radiographic zones affected by disease (p < 0.001). In conclusion, although mortality among patients with PTB is strongly associated with HIV infection in this community, other factors identified reflect late diagnosis, poor treatment compliance and inadequate resources for diagnosis and treatment of TB in rural areas. Improved rates of diagnosis, enhancement of treatment compliance and decentralization of TB services to the district level may therefore help to reduce mortality from TB.

Evidence from a Ghanaian population of known African descent to support the proposition that hemochromatosis is a Caucasian disorder.

Mutations in the HFE gene on chromosome 6 are believed to cause the iron overload disorder hemochromatosis, the most common single gene disorder in northern Europeans. Two mutations have been described previously: C282Y, with an allele frequency of between 3% and 10% in the caucasian population, and H63D, which has an allele frequency of 16%. Published data shows that C282Y appears to be causative in the homozygous state, while the frequency of H63D/C282Y compound heterozygotes is much greater than expected in patient groups. There also appears to be a slightly elevated risk for H63D homozygotes. Hemochromatosis has been thought to be primarily a caucasian disorder. We have studied 97 healthy, black Ghanaian subjects, whose parents and grandparents were also African, to find the frequency of the two mutations. C282Y was absent, while H63D occurred in 2 individuals. These differences are significant at the 0.05 and 0.001 levels, respectively. The prevalence of H63D homozygotes in this population at 1 in 10,000 is clearly of no use in studying the effect of this genotype on phenotype. However, this study suggests an absence of the C282Y mutation in African populations, and the possibility that other populations might provide different genotypes and hence an analysis of H63D risk. A possible heterozygote advantage for the mutation is discussed.