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1.
Indoor Air ; 27(1): 136-146, 2017 01.
Article in English | MEDLINE | ID: mdl-26880607

ABSTRACT

Low birthweight contributes to as many as 60% of all neonatal deaths; exposure during pregnancy to household air pollution has been implicated as a risk factor. Between 2011 and 2013, we measured personal exposures to carbon monoxide (CO) and fine particulate matter (PM2.5 ) in 239 pregnant women in Dar es Salaam, Tanzania. CO and PM2.5 exposures during pregnancy were moderately high (geometric means 2.0 ppm and 40.5 µg/m3 ); 87% of PM2.5 measurements exceeded WHO air quality guidelines. Median and high (75th centile) CO exposures were increased for those cooking with charcoal and kerosene versus kerosene alone in quantile regression. High PM2.5 exposures were increased with charcoal use. Outdoor cooking reduced median PM2.5 exposures. For PM2.5 , we observed a 0.15 kg reduction in birthweight per interquartile increase in exposure (23.0 µg/m3 ) in multivariable linear regression; this finding was of borderline statistical significance (95% confidence interval 0.30, 0.00 kg; P = 0.05). PM2.5 was not significantly associated with birth length or head circumference nor were CO exposures associated with newborn anthropometrics. Our findings contribute to the evidence that exposure to household air pollution, and specifically fine particulate matter, may adversely affect birthweight.


Subject(s)
Air Pollution, Indoor/analysis , Carbon Monoxide/analysis , Maternal Exposure/statistics & numerical data , Particulate Matter/analysis , Urban Population/statistics & numerical data , Adolescent , Adult , Air Pollution, Indoor/adverse effects , Birth Weight , Cooking/methods , Female , Humans , Infant, Newborn , Linear Models , Male , Maternal Exposure/adverse effects , Multivariate Analysis , Pregnancy , Prospective Studies , Tanzania , Young Adult
2.
Int J Tuberc Lung Dis ; 21(12): 1251-1257, 2017 12 01.
Article in English | MEDLINE | ID: mdl-29297445

ABSTRACT

BACKGROUND: Reports on tuberculosis (TB) presentation among the elderly in sub-Sahara Africa are scarce at a time when the elderly population is increasing. This dearth of information is likely to lead to an increase in the number of undetected TB cases in the region. OBJECTIVE: To describe TB presentation and response to anti-tuberculosis treatment at 2 months among elderly patients. METHODS: Consecutive patients referred to TB centres in Dar es Salaam, Tanzania, underwent clinical, microbiological and chest X-ray (CXR) evaluations at baseline and after 2 months of anti-tuberculosis treatment. Patients aged 60 years were considered elderly and those aged 18-59 years formed the comparison group. RESULTS: Elderly patients with TB were more likely to have smear-negative TB (76.7% vs. 49.3%, P < 0.0001) and lower-zone lesions on CXR (41% vs. 17%, P < 0.001), but less likely to have cavities on CXR (77.6% vs. 50.4%, P < 0.0001) than the comparison group. Hypertension and diabetes mellitus were more common among the elderly than among controls. Mortality at 2 months was respectively 18.6% and 8.1% among the elderly and among controls. Human immunodeficiency virus infection and smoking increased mortality, while hypertension was associated with reduced mortality. CONCLUSION: TB in the elderly was associated with atypical clinical and radiological presentations. A high index of suspicion could minimise delays in diagnosis and treatment.


Subject(s)
Antitubercular Agents/therapeutic use , Sputum/microbiology , Tuberculosis/diagnosis , Adolescent , Adult , Age Factors , Aged , Cohort Studies , Diabetes Mellitus/epidemiology , Female , Follow-Up Studies , HIV Infections/epidemiology , Humans , Hypertension/epidemiology , Male , Middle Aged , Prospective Studies , Tanzania/epidemiology , Treatment Outcome , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Young Adult
3.
Acta Neurol Scand ; 133(1): 49-54, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25939728

ABSTRACT

OBJECTIVES: The burden of stroke on healthcare services in sub-Saharan Africa (SSA) is increasing. However, long-term outcomes from stroke in SSA are not well described. We aimed to investigate case-fatality and health outcomes for stroke survivors at 7- to 10-year follow-up. MATERIALS AND METHODS: The Tanzanian Stroke Incidence Project (TSIP) recruited incidence stroke cases between 2003 and 2006. We followed up cases in 2013, recording date of death in those who had died. RESULTS: Of 130 stroke cases included in this study, case-fatality and date of death data were available for 124 at 7-10 years post-stroke. Of these, 102 (82.3%) had died by 7 years post-stroke. Functional disability, as measured by the Barthel index immediately post-stroke, was a significant predictor of case-fatality at seven-year follow-up with those with severe disability having an almost four-fold increase in the odds of death compared with those with no, mild or moderate disability. CONCLUSIONS: Case-fatality rates are higher than reported in high-income countries, with post-stroke disability a significant predictor of death. Sustainable interventions to reduce post-stroke disability in this setting should be investigated.


Subject(s)
Disabled Persons , Stroke/diagnosis , Stroke/mortality , Adult , Aged , Cohort Studies , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Stroke/epidemiology , Survival Rate/trends , Tanzania/epidemiology
4.
J Antimicrob Chemother ; 69(12): 3311-9, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25096076

ABSTRACT

OBJECTIVES: To assess the effect of the major efavirenz metabolizing enzyme (CYP2B6) genotype and the effects of rifampicin co-treatment on induction of CYP3A by efavirenz. PATIENTS AND METHODS: Two study arms (arm 1, n = 41 and arm 2, n = 21) were recruited into this study. In arm 1, cholesterol and 4ß-hydroxycholesterol were measured in HIV treatment-naive patients at baseline and then at 4 and 16 weeks after initiation of efavirenz-based antiretroviral therapy. In arm 2, cholesterol and 4ß-hydroxycholesterol were measured among patients taking efavirenz during rifampicin-based tuberculosis (TB) treatment (efavirenz/rifampicin) just before completion of TB treatment and then serially following completion of TB treatment (efavirenz alone). Non-linear mixed-effect modelling was performed. RESULTS: A one-compartment, enzyme turnover model described 4ß-hydroxycholesterol kinetics adequately. Efavirenz treatment in arm 1 resulted in 1.74 (relative standard error = 15%), 3.3 (relative standard error = 33.1%) and 4.0 (relative standard error = 37.1%) average fold induction of CYP3A for extensive (CYP2B6*1/*1), intermediate (CYP2B6*1/*6) and slow (CYP2B6*6/*6) efavirenz metabolizers, respectively. The rate constant of 4ß-hydroxycholesterol formation [mean (95% CI)] just before completion of TB treatment [efavirenz/rifampicin co-treatment, 7.40 × 10(-7) h(-1) (5.5 × 10(-7)-1.0 × 10(-6))] was significantly higher than that calculated 8 weeks after completion [efavirenz alone, 4.50 × 10(-7) h(-1) (4.40 × 10(-7)-4.52 × 10(-7))]. The CYP3A induction dropped to 62% of its maximum by week 8 of completion. CONCLUSIONS: Our results indicate that efavirenz induction of CYP3A is influenced by CYP2B6 genetic polymorphisms and that efavirenz/rifampicin co-treatment results in higher induction than efavirenz alone.


Subject(s)
Anti-HIV Agents/pharmacokinetics , Antitubercular Agents/pharmacokinetics , Benzoxazines/pharmacokinetics , Cytochrome P-450 CYP2B6/genetics , Cytochrome P-450 CYP3A/metabolism , Hydroxycholesterols/analysis , Rifampin/pharmacokinetics , Adult , Alkynes , Anti-HIV Agents/therapeutic use , Antitubercular Agents/therapeutic use , Benzoxazines/therapeutic use , Cyclopropanes , Female , Genotype , HIV Infections/drug therapy , Humans , Male , Middle Aged , Rifampin/therapeutic use , Tuberculosis/drug therapy
5.
Epidemiol Infect ; 142(7): 1505-9, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24093552

ABSTRACT

Limited studies exist regarding whether incorporating micronutrient supplements during tuberculosis (TB) treatment may improve cell-mediated immune response. We examined the effect of micronutrient supplementation on lymphocyte proliferation response to mycobacteria or T-cell mitogens in a randomized trial conducted on 423 patients with pulmonary TB. Eligible participants were randomly assigned to receive a daily dose of micronutrients (vitamins A, B-complex, C, E, and selenium) or placebo at the time of initiation of TB treatment. We found no overall effect of micronutrient supplements on lymphocyte proliferative responses to phytohaemagglutinin or purified protein derivatives in HIV-negative and HIV-positive TB patients. Of HIV-negative TB patients, the micronutrient group tended to show higher proliferative responses to concanavalin A than the placebo group, although the clinical relevance of this finding is not readily notable. The role of nutritional intervention in this vulnerable population remains an important area of future research.


Subject(s)
Dietary Supplements , Micronutrients/administration & dosage , T-Lymphocytes/drug effects , Tuberculosis, Pulmonary/diet therapy , Tuberculosis, Pulmonary/immunology , Adult , Antitubercular Agents/administration & dosage , Cells, Cultured , Double-Blind Method , Female , HIV Infections/microbiology , Humans , Lymphocyte Activation/drug effects , Male , Phytohemagglutinins/administration & dosage , T-Lymphocytes/cytology , T-Lymphocytes/immunology , Tanzania/epidemiology , Tuberculin/administration & dosage , Tuberculosis, Pulmonary/virology , Young Adult
6.
East Afr J Public Health ; 9(2): 70-3, 2012 Jun.
Article in English | MEDLINE | ID: mdl-23139960

ABSTRACT

BACKGROUND: Hypertension among diabetics is a well recognized cardiovascular risk factor. This study aimed at determining the prevalence of hypertension, its control and the prevalence of other cardiovascular risk factors among diabetic patients. METHODS: We consecutively enrolled 150 adult diabetics. Their age, sex weight, height, blood pressure, fasting capillary blood glucose, lipid and renal profiles, hypertension and diabetes therapy were ascertained. RESULTS: Hypertension prevalence was 54.7%. Treatment and control rates of hypertension were 81.7% and 34% respectively. Hypertensive patients were older, more overweight/obese, had a longer duration of diabetes and elevated serum creatinine. The prevalence of Dyslipidemia, overweight and obesity were 88%, 48.7% and 18.7% respectively. Poor diabetes control was observed in 76.7% of patients. Cigarette smoking was uncommon. CONCLUSION: Hypertension, hyperglycemia, dyslipidemia and obesity are prevalent among our diabetic patients. Both hypertension and glycemia were poorly controlled. Addressing individuals' global cardiovascular risk profiles is vital in diabetics.


Subject(s)
Diabetes Complications/prevention & control , Diabetes Mellitus/physiopathology , Adult , Age Distribution , Age Factors , Aged , Antihypertensive Agents/therapeutic use , Blood Glucose/analysis , Blood Pressure/drug effects , Body Mass Index , Cardiovascular Diseases/epidemiology , Cross-Sectional Studies , Diabetes Mellitus/epidemiology , Dyslipidemias/epidemiology , Female , Hospitals , Humans , Hypertension/complications , Hypertension/drug therapy , Hypertension/epidemiology , Male , Middle Aged , Obesity/epidemiology , Prevalence , Risk Factors , Sex Factors , Socioeconomic Factors , Tanzania/epidemiology , Young Adult
7.
East Afr J Public Health ; 9(1): 10-2, 2012 Mar.
Article in English | MEDLINE | ID: mdl-23120942

ABSTRACT

BACKGROUND: Respiratory infections such as pulmonary tuberculosis (PTB) and pneumonia are significant causes of morbidity and mortality in HIV infection. Recent studies have shown an increase in Pneumocystis jerovecii pneumonia (PCP) in Sub-Saharan Africa. This study determines the prevalence of PCP and other pulmonary infections among HIV patients at HIV clinics in Tanzania. METHODS: HIV infected patients with cough were enrolled between May and November 2006. Sputum induction was done and examined for PCP using Toluidine blue stain and Polymerase chain reaction. Ziehl-Neelsen stain was also done for PTB. RESULTS: Nine of the 125 (7.2%) had smear positive PTB. PCP was diagnosed in 10.4% (13/125) by Toluidine blue, while PCR was positive in 3.6% (3/88). Low CD4+ cell counts were associated with increased risk to both PCP and PTB. CONCLUSION: PCP is still low in Tanzania. PTB remains the major respiratory problem in HIV patients with cough. Toluidine blue staining is not reliable for PCP diagnosis


Subject(s)
AIDS-Related Opportunistic Infections/diagnosis , HIV Infections/complications , Pneumocystis carinii/isolation & purification , Pneumonia, Pneumocystis/complications , Pneumonia, Pneumocystis/diagnosis , Tuberculosis, Pulmonary/complications , AIDS-Related Opportunistic Infections/complications , AIDS-Related Opportunistic Infections/epidemiology , Adolescent , Adult , Aged , CD4 Lymphocyte Count , Cough/complications , Female , HIV Infections/epidemiology , Hospitals , Humans , Male , Middle Aged , Pneumonia, Pneumocystis/epidemiology , Polymerase Chain Reaction , Prevalence , Sex Distribution , Socioeconomic Factors , Sputum/microbiology , Staining and Labeling , Tanzania/epidemiology , Tolonium Chloride , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology
8.
HIV Med ; 13(9): 541-8, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22416813

ABSTRACT

BACKGROUND: Alanine aminotransferase (ALT) is commonly used to measure liver injury in resource-limited settings. Elevations in ALT are predictive of increased mortality from liver disease and may influence the choice of first-line antiretroviral therapy (ART). METHODS: A cross-sectional analysis of the prevalence and predictors of elevated ALT (defined as >40 IU/L) was conducted. ART-naïve, HIV-infected adults with a baseline ALT measurement who were enrolled in any of the 18 HIV Care and Treatment Clinics in Dar es Salaam, Tanzania between November 2004 and December 2009 were included in the study. Median values were calculated and log-binomial regression models were used to examine predictors of elevated ALT. RESULTS: During the study period, 41891 adults had a baseline ALT measurement performed. The prevalence of ALT >40, >120 and >200 IU/L was 13, 1 and 0.3%, respectively. In multivariate analyses, male sex, CD4 T lymphocyte count <200 cells/µL and higher World Health Organization (WHO) clinical stages were associated with a significantly higher risk of ALT >40 IU/L (all P<0.01). Hypertryglyceridaemia, hyperglycaemia and hepatitis B virus (HBV) coinfection (positive for HBV surface antigen) were significantly associated with a higher risk of elevated ALT. Pregnancy, anaemia, low-density lipoprotein cholesterol >130 mg/dL and current tuberculosis treatment were associated with a significantly reduced risk for elevated ALT. CONCLUSIONS: In this HIV-infected, ART-naïve Tanzanian population, extreme elevations in ALT were infrequent but minor elevations were not uncommon. Antiretrovirals with potentially hepatotoxic side effects should be initiated with caution in male patients, and in patients with HBV coinfection, advanced immunosuppression and components of the metabolic syndrome.


Subject(s)
Alanine Transaminase/blood , DNA, Viral/metabolism , HIV Seropositivity/blood , Hepatitis, Viral, Human/blood , Pregnancy Complications, Infectious/blood , RNA, Viral/metabolism , Adult , CD4 Lymphocyte Count , Cross-Sectional Studies , Female , HIV Seropositivity/epidemiology , Hepatitis, Viral, Human/epidemiology , Humans , Male , Middle Aged , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/virology , Prevalence , Risk Factors , Tanzania/epidemiology , Urban Population/statistics & numerical data , Viral Load , Young Adult
9.
S Afr Med J ; 103(2): 107-12, 2012 Dec 11.
Article in English | MEDLINE | ID: mdl-23374304

ABSTRACT

BACKGROUND: This study aimed to identify correlates of case fatality within an incident stroke population in rural Tanzania. METHODS: Stroke patients, identified by the Tanzanian Stroke Incidence Project, underwent a full examination and assessment around the time of incident stroke. Records were made of demographic data, blood pressure, pulse rate and rhythm, physical function (Barthel index), neurological status (communication, swallowing, vision, muscle activity, sensation), echocardiogram, chest X-ray and computed tomography (CT) head scan. Cases were followed up over the next 3 - 6 years. RESULTS: In 130 incident cases included in this study, speech, language and swallowing problems, reduced muscle power, and reduced physical function were all significantly correlated with case fatality at 28 days and 3 years. Age was significantly correlated with case fatality at 3 years, but not at 28 days post-stroke. Smoking history was the only significant correlate of case fatality at 28 days that pre-dated the incident stroke. All other significant correlates were measures of neurological recovery from stroke. CONCLUSIONS: This is the first published study of the correlates of post-stroke case fatality in sub-Saharan Africa (SSA) from an incident stroke population. Case fatality was correlated with the various motor impairments resulting from the incident stroke. Improving poststroke care may help to reduce stroke case fatality in SSA.


Subject(s)
Rural Population , Stroke/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Retrospective Studies , Survival Rate/trends , Tanzania/epidemiology , Time Factors , Young Adult
10.
Clin Pharmacol Ther ; 90(3): 406-13, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21814190

ABSTRACT

We performed a prospective comparative study to examine, from a pharmacogenetics perspective, the effect of rifampicin (RIF) on long-term efavirenz (EFV) autoinduction and kinetics. In a study population of patients with HIV receiving EFV with RIF (arm 2, n = 54) or without RIF (arm 1, n = 128 controls), intraindividual and interindividual plasma EFV and 8-hydroxyefavirenz levels were compared at weeks 4 and 16 of EFV therapy. In arm 2, RIF was initiated 4 weeks before starting EFV. In controls (arm 1), the plasma EFV was significantly lower whereas 8-hydroxyefavirenz was higher at week 16 as compared to week 4. By contrast, there were no significant differences in plasma EFV and 8-hydroxyefavirenz concentrations over time in arm 2. At week 4, the plasma EFV concentration was significantly lower in arm 2 as compared to arm 1, but no significant differences were observed by week 16. When stratified by CYP2B6 genotype, significant differences were observed only with respect to CYP2B6*1/*1 genotypes. Ours is the first report of the CYP2B6 genotype-dependent effect of RIF on long-term EFV autoinduction.


Subject(s)
Antibiotics, Antitubercular/therapeutic use , Aryl Hydrocarbon Hydroxylases/genetics , Benzoxazines/blood , Oxidoreductases, N-Demethylating/genetics , Reverse Transcriptase Inhibitors/blood , Rifampin/therapeutic use , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Alkynes , Alleles , Anti-HIV Agents/blood , Anti-HIV Agents/metabolism , Anti-HIV Agents/therapeutic use , Antibiotics, Antitubercular/blood , Antiretroviral Therapy, Highly Active , Benzoxazines/metabolism , Benzoxazines/therapeutic use , Cyclopropanes , Cytochrome P-450 CYP2B6 , Cytochrome P-450 CYP3A/genetics , Drug Interactions , Enzyme Induction , Female , Genotype , HIV Infections/drug therapy , HIV Infections/genetics , HIV-1/drug effects , HIV-1/genetics , Humans , Male , Polymorphism, Single Nucleotide , Reverse Transcriptase Inhibitors/metabolism , Reverse Transcriptase Inhibitors/therapeutic use , Rifampin/blood , Tuberculosis/drug therapy , Tuberculosis/genetics
11.
Int J Tuberc Lung Dis ; 15(7): 925-32, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21682966

ABSTRACT

SETTING: Tuberculosis (TB) infected adults attending out-patient TB clinics in Dar es Salaam, Tanzania. OBJECTIVE: To examine the association of anemia with human immunodeficiency virus (HIV) co-infection, indicators of socio-economic status (SES) and anthropometric status in TB-infected adults. DESIGN: Cross-sectional data collection during screening for a clinical trial. RESULTS: Overall, 750 females and 1693 males participated in this study, of whom respectively 49% and 24% were co-infected with HIV-1. Hemoglobin levels were significantly lower in females than in males and in HIV-positive than in HIV-negative participants. HIV co-infection in this antiretroviral-naïve population was also associated with severe anemia (hemoglobin < 85 g/l) in both women (prevalence ratio [PR] = 2.07, 95%CI 1.65-2.59) and men (PR 3.45, 95%CI 2.66-4.47). Although severe anemia was negatively associated with indicators of SES, especially in males, adjustment for SES indicators only marginally changed its association with HIV co-infection. In both sexes, anemia was inversely associated with anthropometric status, independently of HIV infection and SES. CONCLUSION: Among TB-infected adults, anemia is strongly associated with HIV co-infection and anthropometric status, independently of SES indicators. As anemia is a risk factor for morbidity and mortality in both infections, the management of anemia in TB-HIV co-infected patients warrants special attention.


Subject(s)
AIDS-Related Opportunistic Infections/complications , Anemia/epidemiology , HIV Infections/complications , Tuberculosis/complications , AIDS-Related Opportunistic Infections/epidemiology , Adult , Anemia/etiology , Anemia/physiopathology , Anthropometry , Cross-Sectional Studies , Female , HIV Infections/epidemiology , Hemoglobins/metabolism , Humans , Male , Risk Factors , Severity of Illness Index , Sex Factors , Socioeconomic Factors , Tanzania/epidemiology , Tuberculosis/epidemiology , Tuberculosis/etiology , Young Adult
12.
Int J Tuberc Lung Dis ; 15(10): 1380-9, 2011 Oct.
Article in English | MEDLINE | ID: mdl-22283899

ABSTRACT

BACKGROUND: Patients with tuberculosis (TB) often suffer from profound malnutrition. OBJECTIVE: To examine the patterns and predictors of change in nutritional and hemoglobin status during and after TB treatment. METHODS: A total of 471 human immunodeficiency virus (HIV) positive and 416 HIV-negative adults with pulmonary TB were prospectively followed in Dar es Salaam, Tanzania. All patients received 8 months' TB treatment following enrollment. RESULTS: About 40% of HIV-positive and 47% of HIV-negative TB patients had body mass index (BMI) < 18.5 kg/m 2 at baseline, while about 94% of HIV-positive and 84% of HIV-negative participants were anemic at baseline. Both HIV-positive and HIV-negative patients experienced increases in BMI and hemoglobin concentrations over the course of TB treatment. Among HIV- positive patients, older age, low CD4 cell counts, and high viral load were independently associated with a smaller increase in BMI from baseline to 8 months. Fe- male sex, older age, low CD4 cell counts, previous TB infection and less money spent on food were independently associated with a smaller improvement in hemoglobin levels among HIV-positive patients during treatment. CONCLUSION: HIV-positive TB patients, especially those with low CD4 cell counts, showed poor nutritional recovery during TB treatment. Adequate nutritional support should be considered during TB treatment.


Subject(s)
Anemia/epidemiology , Antitubercular Agents/therapeutic use , Hemoglobins/metabolism , Malnutrition/epidemiology , Nutritional Status , Tuberculosis, Pulmonary/drug therapy , Adult , Anemia/blood , Anemia/diagnosis , Anemia/therapy , Biomarkers/blood , Body Mass Index , Coinfection , Female , HIV Infections/epidemiology , Health Status Indicators , Humans , Linear Models , Male , Malnutrition/diagnosis , Malnutrition/therapy , Multivariate Analysis , Nutritional Support , Prospective Studies , Tanzania/epidemiology , Time Factors , Treatment Outcome , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Young Adult
13.
Clin Pharmacol Ther ; 88(5): 676-84, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20881953

ABSTRACT

We investigated the influence of gender and pharmacogenetic variations on long-term efavirenz autoinduction and disposition among patients with HIV in Tanzania (N = 129). Plasma concentrations (at 16 h) of efavirenz and 8-hydroxyefavirenz were quantified at weeks 4 and 16 of therapy. Genotyping was performed to identify cytochrome P450 (CYP) 2B6*6, CYP3A5*3, *6, and *7, and ABCB1-3435 C/T genotypes. There were reductions in the median efavirenz concentration (Wilcoxon matched-pair test P < 0.001) and efavirenz/8-hydroxyefavirenz ratio (P < 0.001) by 19 and 32%, respectively, at week 16 as compared with week 4. The proportion of patients with efavirenz concentration <1 µg/ml at week 16 was higher by 67, 25, and 5% in CYP2B6*1/*1, *1/*6, and *6/*6 genotypes, respectively. The defined therapeutic range based on observed plasma concentrations is affected by the time point of sampling and the CYP2B6 genotype. The effect of efavirenz autoinduction on reducing plasma exposure continues up to week 16 and predominantly affects CYP2B6 extensive metabolizers. Among CYP2B6 slow metabolizers, the presence of a CYP3A5 genotype allele is associated with greater effects of efavirenz autoinduction on plasma concentrations of the drug. The cumulative induction may influence the long-term antiretroviral therapy outcome, particularly in CYP2B6*1 carriers.


Subject(s)
Benzoxazines/pharmacokinetics , HIV Infections/drug therapy , Reverse Transcriptase Inhibitors/pharmacokinetics , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Adult , Alkynes , Antiretroviral Therapy, Highly Active , Aryl Hydrocarbon Hydroxylases/genetics , Aryl Hydrocarbon Hydroxylases/metabolism , Benzoxazines/administration & dosage , Benzoxazines/blood , Biotransformation , Cyclopropanes , Cytochrome P-450 CYP2B6 , Cytochrome P-450 CYP3A/genetics , Cytochrome P-450 CYP3A/metabolism , Drug Administration Schedule , Female , Genotype , HIV Infections/blood , Humans , Hydroxylation , Male , Middle Aged , Oxidoreductases, N-Demethylating/genetics , Oxidoreductases, N-Demethylating/metabolism , Phenotype , Prospective Studies , Reverse Transcriptase Inhibitors/administration & dosage , Reverse Transcriptase Inhibitors/blood , Sex Factors , Tanzania
14.
Eur J Clin Nutr ; 64(8): 808-17, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20517330

ABSTRACT

BACKGROUND/OBJECTIVES: There is limited published research examining lipid-soluble vitamins in human immunodeficiency virus (HIV)-infected pregnant women, particularly in resource-limited settings. SUBJECTS/METHODS: This is an observational analysis of 1078 HIV-infected pregnant women enrolled in a trial of vitamin supplementation in Tanzania. Baseline data on sociodemographic and anthropometric characteristics, clinical signs and symptoms, and laboratory parameters were used to identify correlates of low plasma vitamin A (<0.7 micromol/l), vitamin D (<80 nmol/l) and vitamin E (<9.7 micromol/l) status. Binomial regression was used to estimate risk ratios and 95% confidence intervals. RESULTS: Approximately 35, 39 and 51% of the women had low levels of vitamins A, D and E, respectively. Severe anemia (hemoglobin <85 g/l; P<0.01), plasma vitamin E (P=0.02), selenium (P=0.01) and vitamin D (P=0.02) concentrations were significant correlates of low vitamin A status in multivariate models. Erythrocyte Sedimentation Rate (ESR) was independently related to low vitamin A status in a nonlinear manner (P=0.01). The correlates of low vitamin D status were CD8 cell count (P=0.01), high ESR (ESR >81 mm/h; P<0.01), gestational age at enrollment (nonlinear; P=0.03) and plasma vitamins A (P=0.02) and E (P=0.01). For low vitamin E status, the correlates were money spent on food per household per day (P<0.01), plasma vitamin A concentration (nonlinear; P<0.01) and a gestational age <16 weeks at enrollment (P<0.01). CONCLUSIONS: Low concentrations of lipid-soluble vitamins are widely prevalent among HIV-infected women in Tanzania and are correlated with other nutritional insufficiencies. Identifying HIV-infected persons at greater risk of poor nutritional status and infections may help inform design and implementation of appropriate interventions.


Subject(s)
Avitaminosis/epidemiology , HIV Infections/blood , Nutritional Status , Vitamin A/blood , Vitamin D/blood , Vitamin E/blood , Adolescent , Adult , Anemia, Iron-Deficiency/epidemiology , Anemia, Iron-Deficiency/etiology , Avitaminosis/blood , Avitaminosis/complications , Blood Sedimentation , CD8-Positive T-Lymphocytes/metabolism , Cell Count , Diet/economics , Female , Gestational Age , HIV Infections/complications , Hemoglobins/metabolism , Humans , Pregnancy , Prevalence , Regression Analysis , Selenium/blood , Tanzania/epidemiology , Vitamin A Deficiency/blood , Vitamin A Deficiency/complications , Vitamin A Deficiency/epidemiology , Vitamin D Deficiency/blood , Vitamin D Deficiency/complications , Vitamin D Deficiency/epidemiology , Vitamin E Deficiency/blood , Vitamin E Deficiency/complications , Vitamin E Deficiency/epidemiology , Young Adult
15.
Trop Med Int Health ; 14(10): 1226-32, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19732408

ABSTRACT

OBJECTIVE: To evaluate various strategies aimed at improving adherence to antiretroviral therapy (ART). METHODS: Patients initiated on ART at Muhimbili National Hospital HIV clinic were randomly assigned to either regular adherence counseling, regular counseling plus a calendar, or regular counseling and a treatment assistant. Patients were seen monthly; during these meetings self-reported adherence to treatment was recorded. Disease progression was monitored clinically and immunologically. RESULTS: Of the 621 patients randomized, 312 received regular counseling only, 242 regular counseling and calendars, while 67 had treatment assistants in addition to regular counseling. The mean (SD) follow-up time was 14.5 (4.6) months. During follow-up 20 (3.2%) patients died, and 102 (16.4%) were lost to follow-up; this was similar in all groups. In 94.8% of all visits, patients reported to have adhered to treatment. In only 39 (0.7%) visits did patients report a < or = 95% adherence. There were no differences in adherence (P = 0.573) or differences in CD4 count and weight changes over time in the interventions. CONCLUSIONS: Good adherence to ART is possible in resource constrained countries. Persistent adherence counseling in clinic settings by itself may be effective in improving adherence to ART.


Subject(s)
Anti-HIV Agents/administration & dosage , Antiretroviral Therapy, Highly Active , Developing Countries , HIV Infections/drug therapy , Medication Adherence/statistics & numerical data , Adult , CD4 Lymphocyte Count , Drug Administration Schedule , Female , Government Programs/organization & administration , HIV Infections/immunology , Humans , International Cooperation , Male , Patient Education as Topic/methods , Prospective Studies , Tanzania/epidemiology
16.
Int J Tuberc Lung Dis ; 10(6): 663-9, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16776454

ABSTRACT

BACKGROUND: Sputum microscopy for acid-fast bacilli (AFB) is the commonest diagnostic method for pulmonary tuberculosis (PTB) in developing countries. The method is reported to be less sensitive in human immunodeficiency virus (HIV) positive compared to negative patients. We determined the bacillary density in sputum of smear-positive PTB patients and related it to the patients' HIV status, CD4 cell count, clinical and demographic characteristics. METHODS: Three sputum samples per patient were examined using microscopy before initiating therapy. The AFB density was graded according to World Health Organization recommendations. The smear with the highest density was used. High bacillary density was defined as >10 AFB/field. HIV status and CD4 cell count were determined according to the national guidelines. RESULTS: Of 844 patients, 433 (51.3%) were HIV-positive. High bacillary density was significantly less common among HIV-positive (39.0%) than -negative (75.7%) patients (prevalence ratio 0.52; 95%CI 0.45-0.59, P < 0.0001). Among HIV-positive patients, the proportion of those with high bacillary density increased progressively with CD4 cell counts (P = 0.003). CONCLUSION: HIV is associated with lower AFB concentration in sputum. The AFB density falls with falling CD4 cell count. Microscopy for AFB in sputum may be less sensitive in diagnosing PTB when HIV infection is present, especially in severely immunocompromised patients.


Subject(s)
HIV Infections/complications , Mycobacterium tuberculosis/isolation & purification , Sputum/microbiology , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/microbiology , Adult , CD4 Lymphocyte Count , Cross-Sectional Studies , Female , HIV Infections/immunology , Humans , Male , Middle Aged , Tuberculosis, Pulmonary/immunology
17.
Eur J Clin Nutr ; 60(2): 163-71, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16234841

ABSTRACT

OBJECTIVE: To examine the impact of HIV coinfection, socioeconomic status (SES) and severity of tuberculosis (TB) on the body composition and anthropometric status of adults with pulmonary TB. DESIGN: Cross-sectional study. SETTING: Five TB clinics in Dar es Salaam, Tanzania. SUBJECTS: A total of 2231 adult men and women diagnosed with pulmonary TB, prior to the initiation of anti-TB therapy. METHODS: We compared the distribution of anthropometric characteristics including body mass index (BMI), mid-upper arm circumference (MUAC), triceps skin-fold (TSF), and arm muscle circumference (AMC) by HIV status, SES characteristics, and indicators of TB severity (bacillary density in sputum and Karnofsky performance score). Similar comparisons were carried out with body composition variables from bioelectrical impedance analysis and albumin concentrations, in a subsample of 731 subjects. RESULTS: In multivariate analysis, HIV infection was significantly associated with lower MUAC and AMC in both men and women, but not with BMI or TSF. Compared to HIV-uninfected women, those who were HIV infected had lower body cell mass (BCM) (adjusted difference = -0.85 kg, P = 0.04), intracellular water (-0.68 l, P = 0.04), and phase angle (-0.52, P = 0.02). Albumin concentrations were significantly lower in both men and women infected with HIV. Among HIV-infected men, CD4 cell counts <200/mm(3) were related to lower intracellular water, BCM, fat-free mass and phase angle. Independent of HIV infection, BMI and MUAC were positively related to SES indicators and the Karnofsky performance score; and inversely related to bacillary density. CONCLUSIONS: HIV infection is associated with indicators of low lean body mass in adults with TB; socioeconomic factors and TB severity are important correlates of wasting, independent of HIV. SPONSORSHIP: The National Institute of Allergy and Infectious Diseases (UO1 AI 45441-01).


Subject(s)
AIDS-Related Opportunistic Infections/complications , Body Composition , HIV Infections/complications , HIV-1 , Social Class , Tuberculosis, Pulmonary/complications , AIDS-Related Opportunistic Infections/pathology , Adult , Anthropometry , Body Mass Index , CD4 Lymphocyte Count , Electric Impedance , Female , HIV Infections/pathology , HIV Wasting Syndrome/complications , HIV Wasting Syndrome/pathology , Humans , Karnofsky Performance Status , Male , Middle Aged , Multivariate Analysis , Severity of Illness Index , Tanzania , Tuberculosis, Pulmonary/pathology , Wasting Syndrome/complications , Wasting Syndrome/pathology
18.
Int J Tuberc Lung Dis ; 9(10): 1105-11, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16229221

ABSTRACT

SETTING: The development of tuberculosis (TB) in HIV-1-infected individuals is associated with accelerated HIV-1 disease progression. OBJECTIVE: To examine the predictors of incident TB in HIV-1-infected Tanzanian women. DESIGN: A prospective cohort of 1078 HIV-1-infected pregnant women was enrolled in a randomized clinical trial to examine the role of vitamin supplements in HIV-1 disease progression and fetal outcomes. RESULTS: Of 1008 women evaluated for TB, 88 (8.7%) developed TB. After controlling for age, education and hemoglobin concentration, in multivariate analysis, low CD4 cell count, elevated erythrocyte sedimentation rate (ESR), decreased mid-upper arm circumference, and high viremia were associated with an increased risk of TB. CD4 <200 vs. > or = 500 cells/mm3 was associated with a 4.44-fold increase in risk of TB (95%CI 2.10-9.40). Individuals with high viremia (> or = 50,000 copies/ml) had a 2.43-fold increase in risk of TB (95%CI 1.24-4.76). Elevated malarial parasite density was slightly associated with a 65% (95%CI 19-85) decreased risk of TB. CONCLUSIONS: The risk of developing TB was elevated among women with low CD4 cell counts, elevated ESR, coinfections with other pathogens, poor nutrition and high viremia. There is a slight inverse association between malarial infection and TB, possibly because treating malaria may reduce the risk of TB.


Subject(s)
AIDS-Related Opportunistic Infections/epidemiology , Pregnancy Complications, Infectious/epidemiology , Tuberculosis/epidemiology , Adult , Arm/anatomy & histology , CD4 Lymphocyte Count , Chi-Square Distribution , Disease Progression , Female , HIV-1 , Humans , Incidence , Predictive Value of Tests , Pregnancy , Pregnancy Outcome , Proportional Hazards Models , Prospective Studies , Randomized Controlled Trials as Topic , Risk Factors , Tanzania/epidemiology , Viral Load , Vitamins/administration & dosage
19.
Int J Tuberc Lung Dis ; 7(8): 804-7, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12921158

ABSTRACT

Serum vitamin A was determined in a cross-sectional study of 100 HIV-positive and -negative tuberculosis patients and 144 blood donors. Tuberculosis patients were seen again after 2 months of treatment. Mean vitamin A was lowest among tuberculosis patients co-infected with HIV, and was lower among HIV-positive than -negative donors. Mean vitamin A rose significantly at 2 months in HIV-negative patients, and not in -positive patients. HIV infection was the strongest predictor of low vitamin A. Vitamin A deficiency is common in tuberculosis and HIV infection, particularly in those patients who are dually infected, and nutritional supplementation may be beneficial.


Subject(s)
HIV Infections/complications , HIV-1 , Tuberculosis, Pulmonary/complications , Vitamin A Deficiency/complications , Vitamin A/blood , Adult , Cross-Sectional Studies , Female , HIV Infections/blood , HIV Infections/drug therapy , Humans , Male , Nutrition Assessment , Tanzania , Tuberculosis, Pulmonary/blood , Tuberculosis, Pulmonary/drug therapy , Vitamin A Deficiency/blood , Vitamin A Deficiency/drug therapy
20.
Tob Control ; 11(3): 210-4, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12198270

ABSTRACT

OBJECTIVES: To describe the prevalence of tobacco smoking in an urban East African population while using a simple validation procedure to examine the degree of under reporting in men and women. DESIGN: A cross sectional population based study in adults (15 years and over) with sampling from a well maintained census register. SETTING: Ilala Ilala, a middle income district of Dar es Salaam, Tanzania. SUBJECTS: An age and sex stratified random sample of 973 men and women. MAIN OUTCOME MEASURES: Self reported smoking status with correction by exhaled alveolar carbon monoxide (EACO). RESULTS: From the 605 participants (response rate 67.9%) age standardised (new world population) smoking prevalence, based on questionnaire and EACO, was 27.0% (95% confidence interval (CI) 20.8% to 33.2%) in males and 5.0% (95% CI 2.8% to 7.2%) in females. The age specific prevalence of smoking was highest in the age group 35-54 years (34.3%) for men and in the over 54 years group (16%) for women. Of those classified as smokers, 7.3% of men and 27.3% of women were reclassified as current smokers based on EACO (> or = 9 parts per million), after they had reported themselves to be an ex- or non-smoker in the questionnaire. CONCLUSIONS: The data suggest: (1) high rates of smoking among men in an urban area of East Africa; and (2) the importance of validating self reports of smoking status, particularly among women.


Subject(s)
Breath Tests , Carbon Monoxide/analysis , Cross-Cultural Comparison , Developing Countries , Smoking/epidemiology , Adolescent , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Sampling Studies , Tanzania , Urban Population/statistics & numerical data
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