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Biomedical subjects

I T Gangaidzo

Publications and source records attributed to I T Gangaidzo.

At least 19 recordsLinked to original sources

Association of pulmonary tuberculosis with increased dietary iron.

To determine whether increased dietary iron could be a risk factor for active tuberculosis, dietary iron history and human immunodeficiency virus (HIV) status were studied in 98 patients with pulmonary tuberculosis and in 98 control subjects from rural Zimbabwe. Exposure to high levels of dietary iron in the form of traditional beer is associated with increased iron stores in rural Africans. HIV seropositivity was associated with a 17.3-fold increase in the estimated odds of developing active tuberculosis (95% confidence interval [95% CI], 7.4-40.6; P<.001), and increased dietary iron was associated with a 3.5-fold increase (95% CI, 1.4-8.9; P=.009). Among patients treated for tuberculosis, HIV seropositivity was associated with a 3.8-fold increase in the estimated hazard ratio of death (95% CI, 1.0-13.8; P=.046), and increased dietary iron was associated with a 1.3-fold increase (95% CI, 0.4-6.4; P=.2). These findings are consistent with the hypothesis that elevated dietary iron may increase the risk of active pulmonary tuberculosis.

Adult↗

Clinical and genetic heterogeneity in hereditary haemochromatosis: association between lymphocyte counts and expression of iron overload.

To identify a new marker of expression of disease, independent of HFE genotype in patients with hereditary haemochromatosis (HHC), the total peripheral blood lymphocyte counts were analysed according to iron status in two groups of subjects with HFE mutations. The groups consisted of 38 homozygotes for C282Y, and 107 heterozygotes for the C282Y or compound heterozygotes for C282Y and H63D. For control purposes, total lymphocyte counts and iron status were also examined in 20 index patients with African dietary iron overload, a condition not associated with HFE mutations, and in 144 members of their families and communities. Mean lymphocyte numbers were lower in C282Y homozygous HHC index subjects with cirrhosis and higher iron stores than in those without cirrhosis and with lower iron burdens [(1.65 +/- 0.43) x 10(6)/mL vs. (2.27 +/- 0.49) x 10(6)/mL; p = 0.008]. Similarly, mean lymphocyte counts were significantly lower in C282Y heterozygotes and C282Y/H63D compound heterozygotes with iron overload and increased serum ferritin concentrations compared to those with normal serum ferritin concentrations (p < 0.05). Statistically significant negative correlations were found, in males, between lymphocyte counts and the total body iron stores, either in C282Y homozygous HHC patients (p = 0.031 in a multiple regression model dependent on age) and in C282Y heterozygotes or C282Y/H63D compound heterozygotes with iron overload (p = 0.029 in a simple linear model). In contrast, lymphocyte counts increased with increasing serum ferritin concentrations among the index subjects with African iron overload (r = 0.324, not statistically significant) and among the members of their families and communities (r = 0.170, p = 0.042). These results suggest that a lower peripheral blood lymphocyte count is associated with a greater degree of iron loading in HFE haemochromatosis but not in African iron overload, and they support the notion that the lymphocyte count may serve as a marker of a non-HFE gene that influences the clinical expression of HFE haemochromatosis.

Adult↗

Dysentery in patients infected with human immunodeficiency virus in Zimbabwe: an emerging role for Schistosoma mansoni and Escherichia coli O157?

Information on bloody diarrhoea in HIV-positives is scarce. A prospective study was therefore performed, in Zimbabwe, to determine and compare the pathogens associated with bloody diarrhoea in 25 antiretroviral-naïve HIV-infected patients and 15 non-HIV-infected patients. Stool cultures and colonic biopsies were performed. Shigella was isolated from 18 (45%) of the subjects, Schistosoma mansoni from eight (16%), Escherichia coli H7:O157 from three (8%) and Campylobacter jejunii from two (5%). There was no evidence of Salmonella, Entamoeba histolytica or cytomegalovirus infection. Shigella dysenteriae type-1 occurred more often in the HIV-negatives than the HIV-positives (P = 0.02). Although HIV-associated bloody diarrhoea in Zimbabwe appears to be most frequently caused by Shigella, it may also be commonly the result of infection with Sc. mansoni or shiga-toxin-producing E. coli. A larger study specifically to examine the role of Sc. mansoni and E. coli O157 is warranted.

AIDS-Related Opportunistic Infections↗

Carbohydrate-deficient transferrin and chronic alcohol ingestion in subjects with transferrin CD-variants.

Carbohydrate-deficient transferrin (CDT) is widely accepted as screening test for excessive alcohol consumption. However, results from subjects with transferrin variants must be interpreted with caution since chromatography-based methods may give false-positive results. Furthermore, due to the co-elution in HPLC or the co-migration in capillary zone electrophoresis (CZE) of the di- and trisialylated C transferrins with the tetrasialylated D peak, exact measurement of CDT is impossible in CD-variants. Therefore, in this study, we tried to offer a different solution, including only the asialo-D, asialo-C, monosialo-D, monosialo-C, disialo-D and trisialo-D transferrins in the CDT calculation and referring to a different cut-off value for CDT in transferrin CD-variants. Comparison of alcohol consumers with teetotalers demonstrated area under the receiver operating characteristic curve of 0.79 and 0.76 for carbohydrate-deficient transferrin, 0.71 and 0.71 for mean corpuscular volume and 0.51 and 0.68 for gamma-glutamyltransferase in 43 subjects with transferrin CD-variants and 225 subjects with CC-phenotypes, respectively. Since false-positive carbohydrate-deficient transferrin results due to a transferrin CD-variant have major social implications, capillary electrophoresis-based or similar methods (HPLC, FPLC) should be preferred in populations carrying a high D-allele frequency.

Adult↗

Impact of HIV infection on meningitis in Harare, Zimbabwe: a prospective study of 406 predominantly adult patients.

OBJECTIVE: To determine the causative organisms and characteristics of patients presenting with features of meningitis. DESIGN: A prospective cross-sectional study. SETTING: Two tertiary university-affiliated hospitals in Harare, Zimbabwe. PATIENTS: Four-hundred and six patients clinically suspected to have meningitis. MAIN OUTCOME MEASURES: Causative organisms of meningitis; clinical and cerebrospinal fluid characteristics. RESULTS: Four-hundred and six predominantly adult (95% were aged > or = 18 years) patients were suspected to have meningitis. Of the 200 patients confirmed to have meningitis, 89 (45%) had cryptococcal meningitis (CM), 54 (27%) had mononuclear meningitis (MM), 31 (16%) had pyogenic meningitis (PM), 24 (12%) had tuberculous meningitis (TBM) and 2 (1%) had undefined meningitis. HIV seropositivity was 100% in CM, 83% in MM, 81% in PM and 88% in TBM patients. In-hospital mortality rate was 38.8% for CM, 34.9% for MM, 68% for PM and 66.7% for TBM. HIV seropositivity was 80% in the 206 patients not found to have meningitis. CONCLUSIONS: All patients suspected to have meningitis had a high HIV sero positivity irrespective of whether they were later confirmed to have meningitis or not. CM was the most common type of meningitis seen. In-hospital mortality was high irrespective of the cause of meningitis.

AIDS-Related Opportunistic Infections↗

Reference range of serum haptoglobin is haptoglobin phenotype-dependent in blacks.

Reference values for serum haptoglobin (Hp), were established in a Black Zimbabwean population. The upper limit (2.15 g/l) is comparable to the one in Caucasians, but the lower limit (0.12 g/l) is much lower than the proposed interim international reference limit (0.3 g/l). Subjects that typed as Hp 0-0 by starch gel electrophoresis technique were retyped using high performance gel permeation chromatography. This resulted in a 32% decrease in the frequency of Hp 0-0, but an increase in Hp 2-2 and Hp 2-1M phenotype frequencies. In the Zimbabwean Blacks, the Hp 0-0 frequency was estimated to be 2.9%. Haptoglobin reference values were found to be Hp phenotype-dependent; highest values were found in Hp 1-1 (median 0.88 g/l; range 0.31-1.69 g/l) and in Hp 2-1 (median 0.90 g/l; range 0.31-2.22 g/l) and lower values (median 0.66 g/l; range 0.13-1.79 g/l) in Hp 2-2 subjects. The Hp 2-1M phenotype was characterized by low reference values (0.18-1.25 g/l) (P<0.05). In three cases of the rare variant Hp Johnson, high Hp concentrations were found (median 1. 57 g/l; range 0.98-1.57 g/l).

Adult↗

Enterocytozoon bieneusi infection in patients without evidence of immunosuppression: two cases from Zimbabwe found to have positive stools by PCR.

Patients infected with human immunodeficiency virus (HIV) often also have intestinal infections with Enterocytozoon bieneusi. Recently, infection with this microsporidian has been described in immunocompetent subjects, mainly from Europe. When the stools of six HIV-negative patients who presented with diarrhoea in Zimbabwe were investigated, using a recently described protocol based on PCR, two patients were found to have E. bieneusi infections. These two individuals presented with a self limited diarrhoea, abdominal cramping and nausea. These data indicate that E. bieneusi may be a more common cause of diarrhoea in Zimbabwe than previously thought. Larger, prospective studies are needed.

Animals↗

Haptoglobin polymorphism and mortality in patients with tuberculosis.

SETTING: A rural Zimbabwean hospital and the surrounding community. OBJECTIVES: To determine whether a particular haptoglobin phenotype is associated with increased susceptibility to clinical pulmonary tuberculosis, and to determine the outcome of treatment for pulmonary tuberculosis according to haptoglobin phenotype. DESIGN: A case-control study, and a prospective cohort study. RESULTS: We studied 98 consecutive patients with sputum-positive pulmonary tuberculosis and 98 sex- and age-matched controls. The haptoglobin (Hp) phenotype distributions did not differ significantly between the tuberculosis patients and controls (P = 0.5). During the 18-month follow-up period after the start of tuberculosis treatment, 6/18 (33%) cases with Hp 2-2 phenotype died compared to 9/47 (19%) with Hp 2-1 and 3/31 (10%) with Hp 1-1. In a logistic regression model, the odds of dying were 6.1-fold greater with Hp 2-2 than with Hp 1-1 (95%CI 1.04-35.1, P = 0.04). CONCLUSION: Our results suggest that there is equal susceptibility to clinical pulmonary tuberculosis disease amongst different haptoglobin phenotypes. Nonetheless, tuberculosis patients with Hp 2-2 phenotype had a higher risk of mortality.

Adult↗

Transferrin polymorphism influences iron status in blacks.

BACKGROUND: Genetic variants of human transferrin (TF) have been described, but little is known about their functional differences. We studied iron status according to TF phenotype in a healthy Zimbabwean population and in subjects at risk of African iron overload. METHODS: The study population consisted of 483 nondrinkers, 31 drinking spouse pairs, and 5 family pedigrees (n = 88) with index cases of iron overload. TF phenotypes were determined using starch gel electrophoresis. To evaluate iron status, serum iron, total iron-binding capacity (TIBC), ferritin, and soluble TF receptors were measured, and the percentage of saturation and the serum iron:TF ratio were calculated. The binding of the TF variants was studied by equilibrium dialysis. RESULTS: The reference population was characterized by a high TF D allele frequency (0.050) and a complete absence of homozygous TF DD individuals. Similar allele frequencies were observed in subjects at risk of African iron overload. In the reference population, male TF CD heterozygotes had significantly lower (P <0.01) values for serum iron, TIBC, TF saturation, and serum iron:TF ratio than the TF CC homozygotes; in females, only TIBC was significantly different. Overall red blood cell indices did not differ according to TF phenotype. In the population at risk of African iron overload, only serum iron:TF ratio was consistently significantly lower in TF CD phenotypes (P <0.05). After equilibrium dialysis, the amount of iron bound by TF was significantly lower (P <0.01) in TF CD individuals. CONCLUSIONS: The present data demonstrate a functional difference between TF phenotypes in blacks.

Adult↗

Intestinal parasites in patients with diarrhea and human immunodeficiency virus infection in Zimbabwe.

OBJECTIVES: To determine the prevalence of intestinal parasites and risk factors for infection associated with diarrhea in HIV-infected patients in Harare, Zimbabwe. DESIGN: Prospective observational study. METHODS: Single stool samples were collected from 88 HIV-infected individuals presenting with diarrhea of greater than 1 week duration. Stools were examined for intestinal parasites using modified acid fast stain, fluorescence- labeled monoclonal antibody for Cryptosporidium parvum, as well as a modified trichrome stain and a PCR-based protocol for Enterocytozoon bieneusi. RESULTS: C. parvum was detected in 9% (seven out of 82) of samples evaluated, but no Cyclospora was detected. E. bieneusi was detected in 18% (10 out of 55) of stool by trichrome staining and in 51% (28 out of 55) of stool examined by PCR. Risk factors for E. bieneusi infection were: living in rural areas, consumption of nonpiped water, contact with cow dung and household contact with an individual with diarrhea. CONCLUSION: E. bieneusi infection was common in HIV-infected patients with diarrhea in Zimbabwe and may be acquired through person-to-person and fecal-oral transmission.

AIDS-Related Opportunistic Infections↗

A traditional beverage prevents iron deficiency in African women of child bearing age.

OBJECTIVE: To determine if a traditional item in the diet might be useful in preventing iron deficiency in African women of child-bearing age. DESIGN: In a prospective study, the iron status of women who did and did not drink traditional beer high in iron and folic acid, was compared. Iron status was determined by a combination of haemoglobin, serum ferritin and transferrin saturation. SETTING: The study was conducted amongst rural villagers in the Murehwa and Zaka districts of Zimbabwe and in Mpumalanga Province, South Africa. SUBJECTS: 112 women aged between 12 and 50 y from a population of 425 rural people participating in on-going family genetic studies. RESULTS: Women who consumed traditional beer had significantly higher serum ferritin concentrations and transferrin saturations compared to non-drinkers (P = 0.0001 and 0.03 respectively). Iron deficiency anaemia was not present in drinkers but the prevalence in non-drinkers was 13%. Forty seven percent of the non-drinkers and only 14% of the drinkers had evidence of iron deficiency (P = 0.002). Six (21%) of the drinkers and none of the non-drinkers had evidence of iron overload (transferrin saturation > 55% and serum ferritin > 400 ug/l). CONCLUSION: We conclude that the consumption of traditional beer, rich in iron, protects women against iron deficiency. While the use of an alcoholic beverage is not ideal, our findings suggest that indigenous cultural practices might be successfully employed or adapted for promoting iron nutrition.

Adolescent↗

Pancytopenia in Zimbabwe.

BACKGROUND: There has been little systematic study of the clinical spectrum of pancytopenia, and the optimal diagnostic approach to pancytopenia remains undefined. METHODS: The authors studied 134 hospitalized pancytopenic patients in Zimbabwe in both consecutive and nonconsecutive fashion. RESULTS: The most common cause of pancytopenia was megaloblastic anemia, followed by aplastic anemia, acute leukemia, acquired immunodeficiency syndrome (AIDS), and hypersplenism. Severe pancytopenia was usually due to aplastic anemia. Patients with aplastic anemia and acute leukemia were usually children, whereas those with megaloblastic anemia were adults. Moderate to severe anemia was noted throughout the series, but was most striking in patients with megaloblastic anemia, aplastic anemia, and acute leukemia. The mean corpuscular volume (MCV) was elevated in most patients with megaloblastic hematopoiesis, aplastic anemia, and acute nonlymphocytic leukemia. Normal or low MCV values were noted in almost one third of patients with megaloblastic anemia. Anisocytosis, poikilocytosis, macroovalocytosis, microcytosis, fragmentation, and teardrop erythrocytes were more prominent on the blood films of patients with megaloblastic anemia. CONCLUSIONS: Megaloblastic anemia, aplastic anemia, and AIDS are the most common causes of pancytopenia in Zimbabwe. Aplasia is the most frequent cause of severe pancytopenia. The authors have formulated tentative guidelines for the evaluation of pancytopenic patients in this setting.

Acquired Immunodeficiency Syndrome↗

Iron overload in urban Africans in the 1990s.

BACKGROUND: In a previously described model, heterozygotes for an African iron loading locus develop iron overload only when dietary iron is high, but homozygotes may do so with normal dietary iron. If an iron loading gene is common, then homozygotes with iron overload will be found even in an urban population where traditional beer, the source of iron, is uncommon. AIMS: To determine whether iron overload and the C282Y mutation characteristic of hereditary haemochromatosis are readily identifiable in an urban African population. METHODS: Histological assessment, hepatocellular iron grading, and dry weight non-haem iron concentration were determined in post mortem tissue from liver, spleen, heart, lungs, and skin. DNA of subjects with elevated hepatic iron indexes was analysed for the C282Y mutation. Iron concentrations in other tissues were compared. RESULTS: A moderate increase (>30 micromol/g) in hepatic iron concentrations was found in 31 subjects (23%; 95% confidence interval 15.9 to 30.1%), and they were considerably elevated (>180 micromol/g) in seven subjects (5.2%; 95% confidence interval 1.5 to 8.9%). Appreciably elevated hepatic iron concentrations were associated with heavy iron deposition in both hepatocytes and macrophages, and either portal fibrosis or cirrhosis. All were negative for the C282Y mutation. Very high concentrations were uncommon in subjects dying in hospital. Concentrations of iron in spleen, heart, lung, and skin were significantly higher in subjects with elevated hepatic iron. CONCLUSIONS: Iron overload is readily identified among urban Africans and is associated with hepatic damage and iron loading of several tissues. The condition is unrelated to the genetic mutation found in hereditary haemochromatosis.

Adult↗

Iron and alcohol content of traditional beers in rural Zimbabwe.

OBJECTIVES: To determine the concentrations of iron and alcohol in traditional beer, as well as how these may be related to the brewing process. DESIGN: Cross sectional study. SETTING/SUBJECTS: Rural communities living in four of Zimbabwe's nine provinces. MAIN OUTCOME MEASURES: Ionic iron concentration and alcohol concentration in 94 different types of alcoholic beverages prepared in rural areas, and 18 commercially produced beers. RESULTS: The commonest types of traditional beer were a seven day beverage called 'doro rematanda', a by-product of this seven day beer called 'muchaiwa,' and a one-day beverage called 'chikokiyana'. Methods of preparation were similar in the four provinces. Median (Q1, Q3) ionic iron concentrations were 52 (31 to 75) mg/L for the seven-day beer (n = 51), 24 (18 to 36) mg/L for muchaiwa (n = 30) and 21 (17 to 63) mg/L for chikokiyana (n = 13). In contrast, ionic iron concentrations in 12 samples of commercially prepared clear beers were 0.1 mg/L and in commercial opaque beer were 3.6 mg/L. Mean (SD) alcohol concentration in traditional beer was 4.1 g/100 ml (+/- 0.873) compared to 2.8 g/100 ml +/- 1.394) in the muchaiwa and 3.6 g/100 ml (+/- 1.445) in the one day brew, chikokiyana. Mean alcohol concentrations in the three commercial beers are reportedly 3.5 g/100 ml in the opaque beer (Scud), and 4.7 to 5.0 g/ml in clear beer (Zambezi and Castle lagers). CONCLUSIONS: Several preparation methods lead to traditional fermented beverages with very high iron concentrations. Measures to prevent dietary iron overload should include all of these beverages in their scope.

Beer↗

Evidence of genetic transmission in African iron overload.

Iron overload in Africa was previously regarded as purely due to excessive iron in traditional beer, but we recently found evidence that transferrin saturation and unsaturated iron binding capacity may be influenced by an interaction between dietary iron content and a gene distinct from any HLA-linked locus. To determine if serum ferritin follows a genetic pattern and to confirm our previous observations, we studied an additional 351 Zimbabweans and South Africans from 45 families ranging in size from two to 54 members. Iron status was characterized with repeated morning measurements of serum ferritin, transferrin saturation, and unsaturated iron binding capacity after supplementation with vitamin C. For each measure of iron status, segregation analysis was consistent with an interaction between a postulated iron-loading gene and dietary iron content (P < .01). In the most likely model, transferrin saturation is 75% and serum ferritin is 985 micrograms/L in a 40-year-old male heterozygote with an estimated beer consumption of 10,000 L, whereas the saturation is 36% and serum ferritin is 233 micrograms/L in an unaffected individual with identical age, sex, and beer consumption. This segregation analysis provides further evidence for a genetic influence on iron overload in Africans.

Adult↗

Cryptococcal meningitis in human immunodeficiency virus-infected patients in Harare, Zimbabwe.

A prospective observational study was conducted over a 10-month period to determine the clinical and laboratory manifestations of cryptococcal meningitis in Zimbabwe, a country where antifungal agents are not widely available. Eighty-nine patients with cryptococcal meningitis (median age, 34 years; range, 11-63 years; 56 males) were identified from 406 patients for whom a clinical diagnosis of meningitis had been made. All patients tested were positive for antibody to human immunodeficiency virus. Cryptococcal meningitis was the first AIDS-defining illness in 88% of patients. Typical presentations were headache, mental impairment, and meningism (median duration, 14 days; range, 1-180 days). The median CD4+ cell count was 70/microL (range, 0-651/microL). The cumulative median survival from the time of diagnosis was 14 days (range, 0-233 days); 22% of patients survived for >30 days. Independent indicators of a good prognosis were not identified. This study provides a unique basis for the development of novel management strategies for patients with cryptococcal meningitis who reside in resource-poor countries.

AIDS-Related Opportunistic Infections↗