Serum levels of copper and iron in dengue fever / Níveis séricos de cobre e ferro na dengue

SUMMARYThe role of trace elements in dengue virulence is not yet known. The present study assessed the serum levels of two micronutrients, copper and iron, in cases of dengue fever. The study involved 96 patients of whom 48 had either severe or non-severe forms of dengue (with and without warning signs), and the remaining 48 were patients with other febrile illnesses (OFI), used as controls. Serum levels of copper and iron were evaluated at admission and by the time of defervescence using commercially available kits. At admission, no difference in the level of serum copper was observed between cases and controls. In the group of dengue cases, the copper level was found to be significantly decreased in severe and non-severe cases with warning signs, compared to non-severe cases without warning signs. In contrast, by the time of defervescence the copper level was found to be increased in all dengue cases compared to OFI controls, but no difference was observed among dengue cases. Unlike OFI controls, dengue cases showed an increasing pattern of copper levels from admission until defervescence. On the other hand, no such significant differences were observed in the serum level of iron in the clinical groups, except for a decreased iron level found in severe cases, compared to non-severe dengue without warning signs. The results show that copper is associated with dengue severity and this finding emphasizes the need to investigate the involvement of trace elements in disease severity so as to improve the prognosis of dengue.

RESUMOO papel dos elementos-traço na virulência da dengue não é ainda conhecido. O presente estudo avaliou os níveis séricos de dois micronutrientes, cobre e ferro, em casos de dengue. O estudo envolveu 96 pacientes dos quais 48 apresentavam dengue grave ou não grave (com ou sem sinais de alerta), e outros 48 pacientes com outras doenças febris (OFI) representaram os controles. Níveis séricos de cobre e ferro foram avaliados na admissão e no momento da defervescência usando kits comerciais disponíveis. À admissão, nenhuma diferença nos níveis séricos de cobre foi observada entre casos e controles. No grupo com dengue, os níveis de cobre se encontravam significativamente reduzidos nos casos graves e não graves com sinais de alerta, em comparação aos casos não graves sem sinais de alerta. Contrariamente, no momento da defervescência os níveis de cobre se encontravam aumentados em todos os casos de dengue em relação aos controles com outras doenças febris (OFI), no entanto, nenhuma diferença foi observada entre os casos de dengue. Diferentemente dos pacientes com outras doenças febris, os casos de dengue mostraram um padrão de elevação dos níveis de cobre do dia da admissão até a defervescência. Por outro lado, estas diferenças não foram observadas em relação aos níveis de ferro entre os dois grupos, com exceção de níveis de ferro reduzidos encontrados nos casos graves, em comparação aos não graves com sinais de alerta. Os resultados mostram que o cobre está associado à gravidade da dengue e esta observação enfatiza a necessidade de investigação do envolvimento de elementostraço na gravidade da doença para melhorar o prognóstico da dengue.

Pattern & correlates of neurocognitive dysfunction in Asian Indian adults with severe obstructive sleep apnoea.

Background & objectives: No published data are available on neurocognitive dysfunction in Asian Indians with obstructive sleep apnoea (OSA). We therefore, studied the pattern and correlates of neurocognitive dysfunction in Indian adults with severe OSA. Methods: Fifty patients aged 25-65 yr with severe OSA (apnoea-hypopnoea index > 30) and 25 age, sex, and education level-matched normal controls were studied. Both groups were administered a standardized battery of neurocognitive tests. Results: Patients with severe OSA had significantly impaired performance on tests of alertness, working memory, response inhibition, problem solving, and executive function. However, the difference in executive function between the groups disappeared after adjusting for delayed information processing. The test scores did not correlate with apnoea-hypopnoea index, arousal index, or Epworth sleepiness score. However, the percentage of time spent at < 90 per cent oxygen saturation had a weak correlation with the number of stroop errors (Spearman’s rho = 0.64; P = 0.033), number of trials required (rho = 0.05; P = 0.02), and perseverative errors on Wisconsin card sorting test (rho = 0.36; P = 0.02). Interpretation & conclusions: Our results suggested that delayed information processing rather than impaired abstract thinking was probably the cause of impaired performance on composite tests of neurocognitive function in patients with severe OSA.

Role of corticosteroids in the treatment of tuberculosis: An evidence-based update.

Corticosteroids are often used as an adjunct in the treatment of various forms of tuberculosis (TB) and for the prevention of complications, such as constrictive pericarditis, hydrocephalus, focal neurological deficits, pleural adhesions, and intestinal strictures. Notwithstanding, they have been proven in clinical trials to improve the following outcomes only — death or disability in human immunodeficiency virus (HIV)-seronegative patients with tubercular meningitis and tubercular pericarditis. Despite a lack of specific evidence for efficacy in HIV co-infected patients with tubercular meningitis or pericarditis, corticosteroids are generally recommended in them as well. Corticosteroids significantly decrease the risk of pleural thickening in patients with tubercular pleural effusion; the clinical significance of this finding, however, is unclear. Recently, it has been demonstrated that use of corticosteroids improve the morbidity in HIV co-infected patients with paradoxical TB immune reconstitution inflammatory syndrome (IRIS). However, evidence favouring the use of corticosteroids in other clinical situations is sparse or lacking. Likewise, the biological mechanisms underlying their beneficial effect in TB meningitis and pericarditis remain poorly understood.

A study of TB-associated immune reconstitution inflammatory syndrome using the consensus case-definition.

Background & objectives: A considerable proportion of patients with HIV associated tuberculosis (TB) started on highly active antiretroviral therapy (HAART) develop immune reconstitution inflammatory syndrome (IRIS), which is difficult to diagnose in a resource-limited setting. In view of the recently proposed consensus case-definitions for TB-IRIS for use in resource-limited settings we undertook this study to describe the incidence and risk factors of TB associated IRIS in a tertiary care hospital and research centre in north India. Methods: Retrospective analysis of antiretroviral treatment (ART) naïve adults started on highly active ART (HAART) from June 2006 to September 2008 was done. Results: Of the 627 patients studied, 237 (38%) had TB at the initiation of HAART. In total, 18 (7.5%) of 237 patients with TB at baseline had paradoxical TB-associated IRIS, and 12 (3%) of 390 patients without TB at baseline developed ART-associated TB. Most IRIS events occurred during the initial 30 days of HAART. Two patients developed TB-associated IRIS after 90 days of HAART. Using univariate analysis, low CD4+ cell count at baseline [64 (28-89) vs. 95 (52-150); P=0.009] and early initiation of HAART [33 (24-41) vs. 48 (35-61) days; P<0.001] were significantly associated with paradoxical TB-associated IRIS. No identifiable risk factors were associated with the development of ART-associated TB. Interpretation & conclusions: A considerable proportion of patients on HAART develop TB-associated IRIS. The consensus case-definition is a useful tool in resource-limited settings for the diagnosis of TB-associated IRIS.

A prospective study of risk factor profile & incidence of deep venous thrombosis among medically-ill hospitalized patients at a tertiary care hospital in northern India.

Background & objectives: Hospitalization for medical-illness is associated with an increased risk of deep venous thrombosis (DVT). However, there are no published data from India addressing at this issue. We sought to study the risk factor profile and the incidence of DVT among hospitalized medically-ill patients, a tertiary care hospital in northern India. Methods: All adults admitted to the medical wards and intensive care unit with level 1 or 2 mobility over a period of two years (July 2006 to July 2008) at the All India Institute of Medical Sciences hospital, New Delhi, were prospectively studied. Patients having DVT at admission or an anticipated hospital stay less than 48 h were excluded. The presence of clinical risk factors for DVT was recorded and laboratory evaluation was done for hypercoagulable state. A routine surveillance venous compression Doppler ultrasonography was performed 12 ± 8 days after hospital admission. Results: Of the 163 patients, 77 (47%) had more than one risk factor for DVT. Five (3%) patients developed DVT; none of them had symptomatic DVT. None of these patients received anticoagulation prior to the development of DVT. The mean age of those who developed DVT was 40 ± 13 (25-50) yr; two of five were male. The incidence rate of DVT was 2.7 per 1000 person-days of hospital stay [95% confidence interval (CI): 0.87 to 6.27]. None of the factors was found to be significantly associated with the risk of DVT. Interpretation & conclusions: In our setting, although many hospitalized medically-ill patients had risk factors for DVT, the absolute risk of DVT was low compared to the western population but clearly elevated compared to non hospitalized patients. Large studies from India are required to confirm our findings.

Prevalence of extensively drug-resistant tuberculosis among patients with multidrug-resistant tuberculosis: a retrospective hospital-based study.

Background & objective: Extensively drug-resistant tuberculosis (XDR-TB) is a difficult-to-treat form of multidrug-resistant tuberculosis (MDR-TB). High rates of XDR-TB have been reported from India. We sought to ascertain the prevalence of XDR-TB among patients with MDR-TB treated at a tertiary care centre in New Delhi, India. Methods: Case records of patients treated for MDR-TB at the All India Institute of Medical Sciences hospital, New Delhi, between 1997 and 2003 were retrospectively reviewed. All patients underwent a pretreatment drug-susceptibility testing (DST) to first- as well as second-line drugs. XDR-TB was defined as TB caused by bacilli showing resistance to rifampicin and isoniazid in addition to any fluoroquinolone and to at least one of the three following injectable drugs: capreomycin, kanamycin, and amikacin. Results: A total of 211 laboratory-confirmed cases of MDR-TB were reviewed. The mean age of the patients was 33 ± 12 yr. Fifty one (24%) patients were females. All patients were sero-negative for human immunodeficiency virus infection. Five of the 211 MDR-TB patients had XDR-TB. The prevalence of XDR-TB was 2.4 per cent among MDR-TB patients. Interpretation & conclusion: Our results showed that XDR-TB was rare among patients with MDR-TB treated between 1997 and 2003 at our centre. Unreported selection bias might have been responsible for the high prevalence of XDR-TB reported in previous hospital-based studies from India.

A clinical prediction rule to identify patients with tuberculosis at high risk for HIV co-infection.

Background & objective: Many patients presenting with tuberculosis (TB) have underlying human immunodeficiency virus (HIV) co-infection. Routine HIV testing, however, is not a component of the national TB control programme in India. We sought to derive and validate a clinical prediction rule, based on clinical and laboratory parameters, to identify patients at high risk for HIV co-infection among those treated for active TB. Methods: Case records of adult patients with active TB treated between 1997 and 2003 at the All India Institute of Medical Sciences hospital, New Delhi were retrospectively reviewed. The data set was randomly split into a training set and a testing set. First a clinical prediction rule was derived by multivariable logistic regression on the training set and was subsequently validated on the testing set. Results: The study group comprised 1074 patients [training set 711 (66%), HIV co-infected 66 (9%); testing set 363 (34%), HIV co-infected 30 (8%)]. In the training set, male gender [odds ratio (95% CI) 5.31(1.52- 18.61)], axillary lymphadenopathy [9.71 (3.24-29.10)], anaemia [7.56 (2.48-23.05)], hypoalbuminaemia [3.67(1.31-10.26)], and reduced triceps skinfold thickness [2.91(0.95-8.89)] were independently associated with HIV co-infection. In the testing set, presence of any two of these five features was 94 per cent (95% CI 84-100%) sensitive and 54 per cent (49-60%) specific for predicting HIV co-infection; negative predictive value was 99 per cent (98-100%). Area under the receiver-operating characteristic curve was 0.93 (0.86-1.0) in the testing set. Interpretation & conclusions: A simple clinical prediction rule based on clinical and laboratory parameters could be used to identify a subgroup of patients, among those treated for active TB in a hospital setting, for targeted HIV testing.

HIV-TB co-infection: epidemiology, diagnosis & management.

HIV/AIDS pandemic has caused a resurgence of TB, resulting in increased morbidity and mortality worldwide. HIV and Mycobacterium tuberculosis have a synergistic interaction; each accentuates progression of the other. Clinical presentation of TB in early HIV infection resembles that observed in immunocompetent persons. In late HIV infection, however, TB is often atypical in presentation, frequently causing extrapulmonary disease. These factors coupled with low sputum smear-positivity, often result in a delayed diagnosis. HIV-infected patients respond well to the standard 6-month antituberculosis treatment regimens, although mortality is high. Antituberculosis treatment is complicated by frequent drug-interactions with highly active antiretroviral therapy (HAART) and adverse drug reactions are more common among HIV-infected patients. Guidelines for the management of patients co-infected with HIV and TB are still evolving. Timely institution of antituberculosis treatment using the directly observed treatment, short-course (DOTS) strategy and HAART markedly improves the outcome of HIV-infected patients with TB.