Regular Cocaine Use Is Associated with Increased Systolic Blood Pressure,Aortic Stiffness and Left Ventricular Mass in Young Otherwise Healthy Individuals

Background

The cardiovascular impact of cocaine use in otherwise healthy individuals who consider themselves ‘social’ users is not well established.

Methods/Results

Twenty regular cocaine users and 20 control subjects were recruited by word-of-mouth. Cardiovascular magnetic resonance was performed to assess cardiac and vascular structure and function. Cocaine users had higher systolic blood pressure compared to non-users (134±11 vs 126±11 mmHg, p = 0.036), a finding independent of age, body surface area, smoking and alcohol consumption. Cocaine use was associated with increased arterial stiffness - reflected by reduced aortic compliance (1.3±0.2 vs 1.7±0.5 cm²×10⁻².mmHg⁻¹, p = 0.004), decreased distensibility (3.8±0.9 vs 5.1±1.4 mmHg⁻¹.10⁻³, p = 0.001), increased stiffness index (2.6±0.6 vs 2.1±0.6, p = 0.005), and higher pulse wave velocity (5.1±0.6 vs 4.4±0.6 m.s⁻¹, p = 0.001). This change in aortic stiffness was independent of vessel wall thickness. Left ventricular mass was 18% higher in cocaine users (124±25 vs 105±16 g, p = 0.01), a finding that was independent of body surface area, and left atrial diameter was larger in the user group than controls (3.8±0.6 vs 3.5±0.3 cm, p = 0.04). The increased left ventricular mass, systolic blood pressure and vascular stiffness measures were all associated with duration and/or frequency of cocaine use. No late gadolinium enhancement or segmental wall motion abnormalities were seen in any of the subjects.

Conclusions

Compared with the non-user control cohort, cocaine users had increased aortic stiffness and systolic blood pressure, associated with greater left ventricular mass. These measures are all well known risk factors for premature cardiovascular events, highlighting the dangers of cocaine use, even in a ‘social’ setting, and have important public health implications.     

Computational Modeling Reveals Distinct Effects of HIV and History of Drug Use on Decision-Making Processes in Women

Objective

Drug users and HIV-seropositive individuals often show deficits in decision-making; however the nature of these deficits is not well understood. Recent studies have employed computational modeling approaches to disentangle the psychological processes involved in decision-making. Although such approaches have been used successfully with a number of clinical groups including drug users, no study to date has used computational modeling to examine the effects of HIV on decision-making. In this study, we use this approach to investigate the effects of HIV and drug use on decision-making processes in women, who remain a relatively understudied population.

Method

Fifty-seven women enrolled in the Women''s Interagency HIV Study (WIHS) were classified into one of four groups based on their HIV status and history of crack cocaine and/or heroin drug use (DU): HIV+/DU+ (n = 14); HIV+/DU− (n = 17); HIV−/DU+ (n = 14); and HIV−/DU− (n = 12). We measured decision-making with the Iowa Gambling Task (IGT) and examined behavioral performance and model parameters derived from the best-fitting computational model of the IGT.

Results

Although groups showed similar behavioral performance, HIV and DU exhibited differential relationship to model parameters. Specifically, DU was associated with compromised learning/memory and reduced loss aversion, whereas HIV was associated with reduced loss aversion, but was not related to other model parameters.

Conclusions

Results reveal that HIV and DU have differential associations with distinct decision-making processes in women. This study contributes to a growing line of literature which shows that different psychological processes may underlie similar behavioral performance in various clinical groups and may be associated with distinct functional outcomes.     

Illicit Stimulant Use in Humans Is Associated with a Long-Term Increase in Tremor

Use of illicit stimulants such as methamphetamine, cocaine, and ecstasy is a significant health problem. The United Nations Office on Drugs and Crime estimates that 14–57 million people use stimulants each year. Chronic use of illicit stimulants can cause neurotoxicity in animals and humans but the long-term functional consequences are not well understood. Stimulant users self-report problems with tremor whilst abstinent. Thus, the aim of the current study was to investigate the long-term effect of stimulant use on human tremor during rest and movement. We hypothesized that individuals with a history of stimulant use would exhibit abnormally large tremor during rest and movement. Tremor was assessed in abstinent ecstasy users (n = 9; 22±3 yrs) and abstinent users of amphetamine-like drugs (n = 7; 33±9 yrs) and in two control groups: non-drug users (n = 23; 27±8 yrs) and cannabis users (n = 12; 24±7 yrs). Tremor was measured with an accelerometer attached to the index finger at rest (30 s) and during flexion and extension of the index finger (30 s). Acceleration traces were analyzed with fast-Fourier transform. During movement, tremor amplitude was significantly greater in ecstasy users than in non-drug users (frequency range 3.9–13.3 Hz; P<0.05), but was unaffected in cannabis users or users of amphetamine-like drugs. The peak frequency of tremor did not significantly differ between groups nor did resting tremor. In conclusion, abstinent ecstasy users exhibit an abnormally large tremor during movement. Further work is required to determine if the abnormality translates to increased risk of movement disorders in this population.     

Illicit Stimulant Use Is Associated with Abnormal Substantia Nigra Morphology in Humans

Use of illicit stimulants such as methamphetamine, cocaine, and ecstasy is an increasing health problem. Chronic use can cause neurotoxicity in animals and humans but the long-term consequences are not well understood. The aim of the current study was to investigate the long-term effect of stimulant use on the morphology of the human substantia nigra. We hypothesised that history of illicit stimulant use is associated with an abnormally bright and enlarged substantia nigra (termed ‘hyperechogenicity’) when viewed with transcranial sonography. Substantia nigra morphology was assessed in abstinent stimulant users (n = 36; 31±9 yrs) and in two groups of control subjects: non-drug users (n = 29; 24±5 yrs) and cannabis users (n = 12; 25±7 yrs). Substantia nigra morphology was viewed with transcranial sonography and the area of echogenicity at the anatomical site of the substantia nigra was measured at its greatest extent. The area of substantia nigra echogenicity was significantly larger in the stimulant group (0.273±0.078 cm²) than in the control (0.201±0.054 cm²; P<0.001) and cannabis (0.202±0.045 cm²; P<0.007) groups. 53% of stimulant users exhibited echogenicity that exceeded the 90^th percentile for the control group. The results of the current study suggest that individuals with a history of illicit stimulant use exhibit abnormal substantia nigra morphology. Substantia nigra hyperechogenicity is a strong risk factor for developing Parkinson''s disease later in life and further research is required to determine if the observed abnormality in stimulant users is associated with a functional deficit of the nigro-striatal system.     

Milk Consumption and Cardiovascular Risk Factors in Older Chinese: The Guangzhou Biobank Cohort Study

Background

Dairy products consumption is increasingly common globally. Most of the evidence concerning dairy products comes from observational studies in western populations which are inevitably open to confounding. To triangulate the evidence concerning dairy products, we examined the associations of whole cow''s milk consumption with cardiovascular risk factors in a non-Western setting with a different pattern of milk consumption and cardiovascular diseases from Western populations.

Methods

We used multivariable censored linear or logistic regression to examine cross-sectionally the adjusted associations of whole cow''s milk consumption (none (n = 14892), 1–3/week (n = 2689) and 3+/week (n = 2754)) with cardiovascular risk factors in Chinese (≥50 years) in the Guangzhou Biobank Cohort Study.

Results

Whole cow''s milk consumption was negatively associated with systolic blood pressure (3+/week compared to none −2.56 mmHg, 95% confidence interval (CI) −3.63 to −1.49), diastolic blood pressure (−1.32 mmHg, 95% CI −1.87 to −0.77) and triglycerides (−0.06 mmol/L, 95% CI −0.11 to −0.002), but was positively associated with HDL-cholesterol (0.02 mmol/L,95% CI 0.01 to 0.04) and fasting glucose (0.08 mmol/L, 95% CI 0.01 to 0.16) adjusted for age, sex, phase of study, socio-economic position, lifestyle (smoking, alcohol use and physical activity) and adiposity, but had no obvious association with LDL-cholesterol or the presence of diabetes.

Conclusions

Whole cow''s milk consumption had heterogeneous associations with cardiovascular risk factors. Higher whole cow''s milk consumption was associated with lower levels of specific cardiovascular risk factors which might suggest risk factor specific biological pathways with different relations to blood pressure and lipids than glucose.     

Knowledge of Malaria and Its Association with Malaria-Related Behaviors—Results from the Malaria Indicator Survey,Ethiopia, 2007

Background

In 2005, the Ministry of Health in Ethiopia launched a major effort to distribute over 20 million long-lasting insecticidal nets, provide universal access to artemisinin-based combination therapy (ACTs), and train 30,000 village-based health extension workers.

Methods and Findings

A cross-sectional, nationally representative Malaria Indicator Survey was conducted during the malaria transmission season in 2007. Multivariate logistic regression analyses were performed to assess the effect of women''s malaria knowledge on household ITN ownership and women''s ITN use. In addition, we investigated the effect of mothers'' malaria knowledge on their children under 5 years of age''s (U5) ITN use and their access to fever treatment on behalf of their child U5. Malaria knowledge was based on a composite index about the causes, symptoms, danger signs and prevention of malaria. Approximately 67% of women (n = 5,949) and mothers of children U5 (n = 3,447) reported some knowledge of malaria. Women''s knowledge of malaria was significantly associated with household ITN ownership (adjusted Odds Ratio [aOR] = 2.1; 95% confidence interval [CI] 1.6–2.7) and with increased ITN use for themselves (aOR = 1.8; 95% CI 1.3–2.5). Knowledge of malaria amongst mothers of children U5 was associated with ITN use for their children U5 (aOR = 1.6; 95% CI 1.1–2.4), but not significantly associated with their children U5 seeking care for a fever. School attendance was a significant factor in women''s ITN use (aOR = 2.0; 95% CI 1.1–3.9), their children U5′s ITN use (aOR = 4.4; 95% CI 1.6–12.1), and their children U5 having sought treatment for a fever (aOR = 6.5; 95% CI 1.9–22.9).

Conclusions

Along with mass free distribution of ITNs and universal access to ACTs, delivery of targeted malaria educational information to women could improve ITN ownership and use. Efforts to control malaria could be influenced by progress towards broader goals of improving access to education, especially for women.     

Serotonin Impairment in CSF of PD Patients,without an Apparent Clinical Counterpart

In Parkinson''s disease (PD), several studies have detected an impaired serotonin (5-HT) pathway, likely affecting both motor and non-motor domains. However, the precise impact of 5-HT impairment is far from established. Here, we have used a HPLC chromatographic method, in a homogenous cohort (n = 35) of non fluctuating, non dyskinetic PD patients, to assess the concentration of 5-HT and its metabolite 5-HIAA in peripheral cerebrospinal fluid (CSF) obtained from lumbar puncture (LP). LP was performed following three days of therapy withdrawal, in order to vanish the effects of prolonged released dopamine agonists (DA), and in absence of any serotonergic agent. The PD patient group showed a significantly reduced CSF level of both 5-HT and 5-HIAA compared to either age-matched control subjects (n = 18), or Alzheimer''s disease patients (n = 20). However, no correlation emerged between 5-HT/5-HIAA concentrations and UPDRS-III (r = −0.12), disease duration (r = −0.1), age (r = −0.27) and MMSE (r = 0.11). Intriguingly, low CSF 5-HT levels did not differ for gender or for motor phenotype (in terms of non-tremor dominant subtype and tremor dominant subtype). Further, low CSF 5-HT levels did not correlate with the presence of depression, apathy or sleep disturbance. Our findings support the contention that 5-HT impairment is a cardinal feature of stable PD, probably representing a hallmark of diffuse Lewy bodies deposition in the brainstem. However, clinical relevance remains uncertain. Given these findings, an add-on therapy with serotonergic agents seems questionable in PD patients, or should be individually tailored, unless severe depression is present.     

Organisational Culture in Residential Aged Care Facilities: A Cross-Sectional Observational Study

Background

Organisational culture is increasingly recognised as important for provision of high-quality long-term care. We undertook this study to measure organisational culture in residential aged care facilities in two Australian states.

Methodology/Principal Findings

Cross-sectional observational study in 21 residential aged care facilities in Western Australia (n = 14) and Queensland (n = 7), Australia. Staff and next-of-kin of residents participated. Measurement comprised surveys of facility staff and residents'' next-of-kin, and structured observation of indicators of care quality. Staff tended to rate organisational culture positively. Some qualitative feedback from staff emphasised negative perceptions of communication, leadership and teamwork. Staffing levels were perceived as a dominant challenge, threatening care quality. Direct observation revealed variability within and between facilities but suggested that most facilities (n = 12) were in the typical range, or were quality facilities (n = 8).

Conclusion

There was scope to strengthen organisational culture in participating aged care facilities.     

Renal Involvement in Non-Hodgkin Lymphoma: Proven by Renal Biopsy

Aims

To determine the spectrum of renal lesions in patients with kidney involvement in non-Hodgkin''s lymphoma (NHL) by renal biopsy.

Methods

The clinical features and histological findings at the time of the renal biopsy were assessed for each patient.

Results

We identified 20 patients with NHL and renal involvement, and the diagnosis of NHL was established following the kidney biopsy in 18 (90%) patients. The types of NHL include the following: chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 8), diffuse large B-cell lymphoma (n = 4), T/NK cell lymphoma (n = 3), lymphoplasmacytic lymphoma (n = 2), cutaneous T-cell lymphoma (n = 1), mucosa-associated lymphoid tissue lymphoma (n = 1) and mantle cell lymphoma (n = 1). All presented with proteinuria, and 15 patients had impaired renal function. The pathological findings included (1) membranoproliferative glomerulonephritis-like pattern in seven patients; (2) crescent glomerulonephritis in four; (3) minimal-change disease in three, and glomeruli without specific pathological abnormalities in three; (4) intraglomerular large B-cell lymphoma in one; (5) intracapillary monoclonal IgM deposits in one; (6) primary diffuse large B-cell lymphoma of the kidneys in one; and (7) lymphoma infiltration of the kidney in eight patients.

Conclusion

A wide spectrum of renal lesions can be observed in patients with NHL, and NHL may be first proven by renal biopsies for evaluation of kidney injury or proteinuria. Renal biopsy is necessary to establish the underlying cause of renal involvement in NHL.     

Stressful Events and Continued Smoking and Continued Alcohol Consumption during Mid-Pregnancy

Aim

to examine whether the severity of different categories of stressful events is associated with continued smoking and alcohol consumption during mid-pregnancy. Also, we explored the explanation of these associations by anxiety and depressive symptoms during pregnancy. Finally, we studied whether the severity of stressful events was associated with the amount of cigarettes and alcohol used by continued users.

Method

we conducted a cross-sectional analysis using data from a population-based prospective cohort study. Pregnant women were recruited via midwifery practices throughout The Netherlands. We analyzed women who continued smoking (n = 113) or quit (n = 290), and women who continued alcohol consumption (n = 124) or quit (n = 1403) during pregnancy. Smoking, alcohol consumption, and perceived severity of stressful events were measured at 19 weeks of gestation. The State Trait Anxiety Inventory and the Edinburgh Postnatal Depression Scale were filled out at 14 weeks of gestation. Odds ratios were calculated as association measures and indicated the relative increase for the odds of continuation of smoking and alcohol consumption for the maximum severity score compared to the minimum score.

Findings

severity of the following stressful event categories was associated with continued alcohol consumption: ‘conflict with loved ones’ (OR = 10.4, p<0.01), ‘crime related’ (OR = 35.7, p<0.05), ‘pregnancy-specific’ (OR = 13.4, p<0.05), and the total including all events (OR = 17.2, p<0.05). Adjustment for potential confounders (age, parity and educational level) did not notably change the estimates. There was no association of anxiety and depressive symptoms with continued smoking or alcohol consumption. No associations emerged for continued smoking and severity of stressful events. The amount of cigarettes and alcohol consumption among continued users was not associated with severity of stressful events.

Conclusions

Our findings may be relevant for health care providers, in particular midwives and general practitioners. The impact of stressful events may be considered when advising pregnant women on smoking and alcohol consumption.     

A Case-Control Study of Maternal Periconceptual and Pregnancy Recreational Drug Use and Fetal Malformation Using Hair Analysis

Objective

Maternal recreational drug use may be associated with the development of fetal malformations such as gastroschisis, brain and limb defects, the aetiology due to vascular disruption during organogenesis. Using forensic hair analysis we reported evidence of recreational drug use in 18% of women with a fetal gastroschisis. Here we investigate this association in a variety of fetal malformations using the same method.

Methods

In a multi-centre study, women with normal pregnancies (controls) and those with fetal abnormalities (cases) gave informed consent for hair analysis for recreational drug metabolites using mass spectrometry. Hair samples cut at the root were tested in sections corresponding to 3 month time periods (pre and periconceptual period).

Results

Women whose fetus had gastroschisis, compared to women with a normal control fetus, were younger (mean age 23.78±SD4.79 years, 18–37 vs 29.79±SD6 years, 18–42, p = 0.00001), were more likely to have evidence of recreational drug use (15, 25.4% vs 21, 13%, OR2.27, 95^thCI 1.08–4.78, p = 0.028), and were less likely to report periconceptual folic acid use (31, 53.4% vs 124, 77.5%, OR0.33, 95^thCI 0.18–0.63, p = 0.001). Age-matched normal control women were no less likely to test positive for recreational drugs than women whose fetus had gastroschisis. After accounting for all significant factors, only young maternal age remained significantly associated with gastroschisis. Women with a fetus affected by a non-neural tube central nervous system (CNS) anomaly were more likely to test positive for recreational drugs when compared to women whose fetus was normal (7, 35% vs 21, 13%, OR3.59, 95^th CI1.20–10.02, p = 0.01).

Conclusions

We demonstrate a significant association between non neural tube CNS anomalies and recreational drug use in the periconceptual period, first or second trimesters, but we cannot confirm this association with gastroschisis. We confirm the association of gastroschisis with young maternal age.     

Transactional Sex Risk across a Typology of Rural and Urban Female Sex Workers in Indonesia: A Mixed Methods Study

Context-specific typologies of female sex workers (FSWs) are essential for the design of HIV intervention programming. This study develops a novel FSW typology for the analysis of transactional sex risk in rural and urban settings in Indonesia. Mixed methods include a survey of rural and urban FSWs (n = 310), in-depth interviews (n = 11), key informant interviews (n = 5) and ethnographic assessments. Thematic analysis categorises FSWs into 5 distinct groups based on geographical location of their sex work settings, place of solicitation, and whether sex work is their primary occupation. Multiple regression analysis shows that the likelihood of consistent condom use was higher among urban venue-based FSWs for whom sex work is not the only source of income than for any of the other rural and urban FSW groups. This effect was explained by the significantly lower likelihood of consistent condom use by rural venue-based FSWs (adjusted OR: 0.34 95% CI 0.13–0.90, p = 0.029). The FSW typology and differences in organisational features and social dynamics are more closely related to the risk of unprotected transactional sex, than levels of condom awareness and availability. Interventions need context-specific strategies to reach the different FSWs identified by this study''s typology.     

Genetic Variation of the Ghrelin Signalling System in Individuals with Amphetamine Dependence

The development of amphetamine dependence largely depends on the effects of amphetamine in the brain reward systems. Ghrelin, an orexigenic peptide, activates the reward systems and is required for reward induced by alcohol, nicotine, cocaine and amphetamine in mice. Human genetic studies have shown that polymorphisms in the pre-proghrelin (GHRL) as well as GHS-R1A (GHSR) genes are associated with high alcohol consumption, increased weight and smoking in males. Since the heritability factor underlying drug dependence is shared between different drugs of abuse, we here examine the association between single nucleotide polymorphisms (SNPs) and haplotypes in the GHRL and GHSR, and amphetamine dependence. GHRL and GHSR SNPs were genotyped in Swedish amphetamine dependent individuals (n = 104) and controls from the general population (n = 310). A case-control analysis was performed and SNPs and haplotypes were additionally tested for association against Addiction Severity Interview (ASI) composite score of drug use. The minor G-allele of the GHSR SNP rs2948694, was more common among amphetamine dependent individuals when compared to controls (p_c = 0.02). A significant association between the GHRL SNP rs4684677 and ASI composite score of drug use was also reported (p_c = 0.03). The haplotype analysis did not add to the information given by the individual polymorphisms. Although genetic variability of the ghrelin signalling system is not a diagnostic marker for amphetamine dependence and problem severity of drug use, the present results strengthen the notion that ghrelin and its receptor may be involved in the development of addictive behaviours and may thus serve as suitable targets for new treatments of such disorders.     

Bacterial Load of Pneumococcal Serotypes Correlates with Their Prevalence and Multiple Serotypes Is Associated with Acute Respiratory Infections among Children Less Than 5 Years of Age

Background

Among pneumococcal serotypes, some serotypes are more prevalent in the nasopharynx than others; determining factors for higher prevalence remain to be fully explored. As non-vaccine serotypes have emerged after the introduction of 7-valent conjugate vaccines, study of serotype specific epidemiology is in need. When two or more serotypes co-colonize, they evolve rapidly to defend host''s immune responses; however, a clear association of co-colonization with a clinical outcome is lacking.

Methods

Children less than 5 years old who were admitted to hospital due to acute respiratory infections (ARI) (n = 595) and healthy children (n = 350) were recruited. Carriage of pneumococcus was determined by culture and lytA PCR in the nasopharyngeal samples. Serotype/serogroup detection and its quantification were done by the nanofluidic real time PCR system. Spearman''s correlation and logistic regression were used to examine a correlation of serotype/serogroup specific bacterial load with its prevalence and an association of co-colonization with ARI respectively.

Results

Serotype/serogroup specific bacterial load was correlated with its prevalence, both in ARI cases (Spearman''s rho = 0.44, n = 186; P<0.0001) and healthy children (Spearman''s rho = 0.41, n = 115; P<0.0001). The prevalence of multiple serotypes was more common in ARI cases than in healthy children (18.5% vs 7.1%; aOR 2.92, 95% CI: 1.27–6.71; P = 0.01). The dominant serotype in the co-colonization had a 2 log10 higher bacterial load than the subdominant serotype, both in ARI cases (P<0.001) and healthy children (P<0.05).

Conclusions

High bacterial load in the nasopharynx may help transmit pneumococci among hosts, and increase the chance of successful acquisition and colonization. Co-colonization of multiple serotypes of pneumococci is linked with ARI, which infers the interactions of multiple serotypes may increase their pathogenicity; however, they may compete for growth in number.     

A Study of Remitted and Treatment-Resistant Depression Using MMPI and Including Pessimism and Optimism Scales

Background

The psychological aspects of treatment-resistant and remitted depression are not well documented.

Methods

We administered the Minnesota Multiphasic Personality Inventory (MMPI) to patients with treatment-resistant depression (n = 34), remitted depression (n = 25), acute depression (n = 21), and healthy controls (n = 64). Pessimism and optimism were also evaluated by MMPI.

Results

ANOVA and post-hoc tests demonstrated that patients with treatment-resistant and acute depression showed similarly high scores for frequent scale (F), hypochondriasis, depression, conversion hysteria, psychopathic device, paranoia, psychasthenia and schizophrenia on the MMPI compared with normal controls. Patients with treatment-resistant depression, but not acute depression registered high on the scale for cannot say answer. Using Student''s t-test, patients with remitted depression registered higher on depression and social introversion scales, compared with normal controls. For pessimism and optimism, patients with treatment-resistant depression demonstrated similar changes to acutely depressed patients. Remitted depression patients showed lower optimism than normal controls by Student''s t-test, even though these patients were deemed recovered from depression using HAM-D.

Conclusions

The patients with remitted depression and treatment-resistant depression showed subtle alterations on the MMPI, which may explain the hidden psychological features in these cohorts.     

Complex Patterns of Genomic Admixture within Southern Africa

Within-population genetic diversity is greatest within Africa, while between-population genetic diversity is directly proportional to geographic distance. The most divergent contemporary human populations include the click-speaking forager peoples of southern Africa, broadly defined as Khoesan. Both intra- (Bantu expansion) and inter-continental migration (European-driven colonization) have resulted in complex patterns of admixture between ancient geographically isolated Khoesan and more recently diverged populations. Using gender-specific analysis and almost 1 million autosomal markers, we determine the significance of estimated ancestral contributions that have shaped five contemporary southern African populations in a cohort of 103 individuals. Limited by lack of available data for homogenous Khoesan representation, we identify the Ju/''hoan (n = 19) as a distinct early diverging human lineage with little to no significant non-Khoesan contribution. In contrast to the Ju/''hoan, we identify ancient signatures of Khoesan and Bantu unions resulting in significant Khoesan- and Bantu-derived contributions to the Southern Bantu amaXhosa (n = 15) and Khoesan !Xun (n = 14), respectively. Our data further suggests that contemporary !Xun represent distinct Khoesan prehistories. Khoesan assimilation with European settlement at the most southern tip of Africa resulted in significant ancestral Khoesan contributions to the Coloured (n = 25) and Baster (n = 30) populations. The latter populations were further impacted by 170 years of East Indian slave trade and intra-continental migrations resulting in a complex pattern of genetic variation (admixture). The populations of southern Africa provide a unique opportunity to investigate the genomic variability from some of the oldest human lineages to the implications of complex admixture patterns including ancient and recently diverged human lineages.     

Clinical Deterioration during Antitubercular Treatment at a District Hospital in South Africa: The Importance of Drug Resistance and AIDS Defining Illnesses

Background

Clinical deterioration on drug therapy for tuberculosis is a common cause of hospital admission in Africa. Potential causes for clinical deterioration in settings of high HIV-1 prevalence include drug resistant Mycobacterium tuberculosis (M.tb), co-morbid illnesses, poor adherence to therapy, tuberculosis associated-immune reconstitution inflammatory syndrome (TB-IRIS) and subtherapeutic antitubercular drug levels. It is important to derive a rapid diagnostic work-up to determine the cause of clinical deterioration as well as specific management to prevent further clinical deterioration and death. We undertook this study among tuberculosis (TB) patients referred to an adult district level hospital situated in a high HIV-1 prevalence setting to determine the frequency, reasons and outcome for such clinical deterioration.

Method

A prospective observational study conducted during the first quarter of 2007. We defined clinical deterioration as clinical worsening or failure to stabilise after 14 or more days of antitubercular treatment, resulting in hospital referral. We collected data on tuberculosis diagnosis and treatment, HIV-1 status and antiretroviral treatment, and investigated reasons for clinical deterioration as well as outcome.

Results

During this period, 352 TB patients met inclusion criteria; 296 were admitted to hospital accounting for 17% of total medical admissions (n = 1755). Eighty three percent of TB patients (291/352) were known to be HIV-1 co-infected with a median CD4 count of 89cells/mm³ (IQR 38–157). Mortality among TB patients admitted to hospital was 16% (n = 48). The median duration of hospital admission was 9.5 days (IQR 4–18), longer than routine in this setting (4 days). Among patients in whom HIV-1 status was known (n = 324), 72% of TB patients (n = 232) had an additional illness to tuberculosis; new AIDS defining illnesses (n = 80) were the most frequent additional illnesses (n = 208) in HIV-1 co-infected patients (n = 291). Rifampin-resistant M.tb (n = 41), TB-IRIS (n = 51) and drug resistant bacterial infections (n = 12) were found in 12%, 14% and 3.4% of the 352 cases, respectively.

Interpretation

In our setting, new AIDS defining illnesses, drug resistant M.tb and other drug resistant bacteria are important reasons for clinical deterioration in HIV-1 co-infected patients receiving antitubercular treatment. HIV-1 co-infected patients may be at increased risk of acquiring nosocomial drug resistant pathogens because profound immune suppression results in co-morbid illnesses that require prolonged inpatient admissions. Routine infection control is essential and needs to be strengthened in our setting.