Acquired alpha 1-antitrypsin deficiency in tropical pulmonary eosinophilia.

Background & objectives: Observation of an increased frequency of an intermediate deficiency of serum alpha1-antitrypsin (α1-AT) in patients with Tropical Pulmonary Eosinophilia (TPE) was earlier reported. Though the possibility of existence of an acquired deficiency was suggested, without phenotyping a hereditary α1-AT deficiency in TPE could not totally be ruled out. In this study, we have done Pi (Protease inhibitor) phenotyping to investigate the possibility of association of any heterozygous (or homozygous) α1-AT deficiency in patients with TPE. Methods: Serum a1antitrypsin (α1-AT) was measured in 103 patients (Group A) with TPE, 99 patients with pulmonary eosinophilia who had associated intestinal worm infestation (Group B) and 43 healthy volunteers who served as controls. In 19 α1-AT deficient patients (9 of Group A and 10 of Group B), α1-AT level was measured before and after treatment. In 58 patients with TPE and in 5 controls, phenotyping was done. Results: Fifteen patients of Group A and 16 from Group B showed intermediate α1-AT deficiency (150 mg % or less. None of the control subjects had α1-AT deficiency (<200 mg%). After treatment with DEC and/or deworming, in 19 patients there was a significant (P < 0.001) rise in α1-AT levels. Results of phenotyping showed that all had M1 or M2 allele and none had S or Z variant (either homozygous or heterozygous) thus ruling out any underlying genetic cause for the observed α1-AT deficiency. Interpretation & conclusions: The observed α1-AT deficiency may be due to the chronic inflammation in TPE and associated oxidative stress. However, in such α1-AT deficient patients with TPE and those with worm infested pulmonary eosinophilia, faecal α1-AT concentration and faecal α1-AT clearance should be routinely estimated to rule out the possibility of any intestinal protein loss.

Pharmacokinetics of lamivudine & stavudine in generic fixed-dose combinations in HIV-1 infected adults in India.

Background & objectives: Antiretroviral drug concentrations are important determinants of clinical response to a drug accounting for both toxicity and efficacy. Several factors such as age, ethnicity, body weight and patients’ immune status may influence antiretroviral drug concentrations. The aim of the study was to determine the influence of immunological status, sex and body mass index on the steady state pharmacokinetics of lamivudine (3TC) and stavudine (d4T) in HIV-infected adults, who were undergoing treatment with generic fixed dose combinations (FDC) of these drugs in India. Methods: Twenty seven HIV-1 infected patients receiving antiretroviral treatment (ART) for at least two weeks at the Government ART clinic at Tambaram, Chennai, took part in the study. Serial blood samples were collected predosing and at different time points after drug administration. Plasma 3TC and d4T levels were estimated by HPLC. Results: The patients’ immune status, sex or body mass index had no impact on the pharmacokinetics of 3TC. In the case of d4T, peak concentration was significantly lower in patients with CD4 cell counts < 200 cells/μl than those with ≥ 200 cells/ μl (P < 0.05), but were within the therapeutic range. The mean CD4 cell counts increased from 101 cells/μl at initiation of ART to 366 cells/μl at 12 months of treatment. Interpretation & conclusions: Blood levels of 3TC and d4T drugs that are part of generic FDCs commonly used by HIV-infected individuals in India were within the therapeutic range and not influenced by nutritional or immune status. There was a significant improvement in CD4 cell counts over 12 months of treatment. Indian generic FDCs manufactured and used widely in the developing world provide effective concentrations of antiretroviral drugs.

Relevance of Anti-BmR1 IgG4 Antibodies in Children from an Area Endemic for Brugia malayi Infection in Kerala, India.

Brugian filariasis prevalent mostly in South-East Asian countries including India contributes to a small but significant proportion of the socioeconomic burden due to lymphatic filariasis. Along with bancroftian filariasis, brugian filariasis has been targeted for elimination globally. The lack of a reliable daytime diagnostic test has been seen as an important barrier to the successful implementation and monitoring of elimination programmes in brugia endemic areas. We evaluated an anti- BmRI-IgG4 antibody test namely, 'Brugia Rapid' in a large study meant to understand the clinical and pathological manifestations of brugian filariasis in children. We found the test superior to traditional night blood screening for microfilaraemia. Although an antibody detection test, we found it to be a reliable indicator of brugian infection. Among the 100 children studied extensively, 94% of the microfilaraemics, 86% of those showing filarial dance sign indicating presence of, live adult worms and 78% having abnormal lymphatics on lymphoscintigraphy were IgG4 positive. Coupled with its advantages like ease of use any time of the day, high sensitivity and specificity, this test may be the ideal tool to assist programme managers in their efforts to eliminate lymphatic filariasis where brugian infections are found.

Lymphoscintigraphic evidence of lymph vessel dilation in the limbs of children with Brugia malayi infection.

Lymphatic filariasis (LF) is targeted for global elimination by the year 2020. It was earlier believed that LF is mostly a disease of adults. Recent studies indicate that in endemic countries filarial infection starts mostly in childhood even though the disease manifestations occur much later in life. The initial damage to the lymph vessels where the adult worms are lodged is dilation, thought to be irreversible even with treatment. Most of these studies relate to bancroftian filariasis. Studies that address this early pathology in brugian filariasis in humans are scarce. We report here for the first time, the lymphatic abnormalities seen on lymphoscintigraphy (LSG) in children with Brugia malayi filariasis. LSG was performed in 100 children aged between 3-15 years, who were enrolled in the study either because they were microfilaremic; had present or past filarial disease or were positive for antifilarial IgG4 antibodies. Inguinal and axillary lymph nodes were imaged in most children. Dilated lymph vessels were visualized in 80 children and this pathology was evenly distributed in all the three study groups. Lymph vessels dilation was seen even in three year old children. The implications of these findings for management of LF and control programmes are discussed.

Urine levels of rifampicin & isoniazid in asymptomatic HIV-positive individuals.

BACKGROUND & OBJECTIVE: AIDS and its associated gastrointestinal complications may impair the absorption of anti-tuberculosis (TB) drugs. Impaired absorption of anti-TB drugs could lead to low drug exposure, which might contribute to acquired drug resistance and reduced effectiveness of anti-TB treatment. The aim of this study was to obtain information on the status of absorption of rifampicin (RMP) and isoniazid (INH) in asymptomatic HIV- positive individuals, who are less immunocompromised. The D-xylose absorption test was also carried out to assess the absorptive capacity of intestive. METHODS: The absorption of RMP, INH and D-xylose was studied in 15 asymptomatic HIV-positive individuals with CD4 cell counts>350 cells/mm3 and 16 healthy volunteers, after oral administration of single doses of RMP (450 mg), INH (300 mg) and D-xylose (5 g). Urine was collected up to 8 h after drug administration. Percentage dose of the drugs and their metabolites and D-xylose excreted in urine were calculated. RESULTS: A significant reduction in the urinary excretion of INH and D-xylose in HIV-positive persons compared to healthy volunteers was observed. The per cent dose of RMP and its metabolite, desacetyl RMP was also lower in HIV-positive persons compared to healthy volunteers, but this difference was not statistically significant. INTERPRETATION & CONCLUSION: Decreased urinary excretion of D-xylose and INH are suggestive of intestinal malabsorption in HIV-positive individuals. HIV infection could cause malabsorption of anti-TB drugs even at an early stage of the disease. The clinical implications of these findings need to be confirmed in larger studies.

A qualitative study on the feasibility and benefits of foot hygiene measures practiced by patients with brugian filariasis.

Disability alleviation is an important component of 'Global Programme for Elimination of Lymphatic Filariasis'. In Brugia malayi infection the disability is largely due to acute attacks of adenolymphangitis (ADL), which frequently prevent patients from attending their normal activities, causing much suffering and economic loss. The foot care programme has been shown to reduce the frequency and severity of these episodes. In the present study we used semi-structured interviews to evaluate the impact of the foot care in 127 patients with brugian filariasis. They were previously trained in this procedure and were advised to practice it regularly, unsupervised. All except one could recollect the various components of foot hygiene and were practicing it regularly. They were aware of the factors causing ADL attacks and were able to avoid them. Majority (95.2%) expressed their happiness with the relief provided by foot care, which prevented or reduced the ADL episodes. The motivation was such that they transmitted this knowledge to others suffering in the community and even physically helped them to carry out foot care. This study fully endorses the advocacy of foot care programme as an easy to carry out, effective, sustainable and economically feasible procedure to prevent acute ADL attacks.

Estimation of ASO titer as an indicator of streptococcal infection precipitating acute adenolymphangitis in brugian lymphatic filariasis.

Recurrent episodes of acute adenolymphangitis (ADL) are important clinical manifestations of lymphatic filariasis which contribute significantly to the progression of lymphedema. It is increasingly being recognized that secondary bacterial infections play an important role in the etiology of ADL. We examined the role of streptococcal infection as a precipitating factor of ADL in brugian filariasis, by determining the anti-streptolysin O (ASO) titers and by isolating the causative organism wherever possible. The study population consisted of 30 patients with filariasis related ADL (Group A), 30 patients with chronic filarial edema (Group B) and 60 age and sex matched healthy adults (Group C). ASO titer was estimated by the latex agglutination method at the time of entry into the study, at the 15th day and at 3, 6 and 12 months. ASO titers were persistently elevated in 90% of patients in Group A and a portal of entry for bacterial infection was detected in all of these patients. In Group B only six patients had persistently elevated ASO titers. These patients had grade III lymphedema and three of them had monilial infections in the affected limb. In the control group none had persistently elevated ASO titers. The elevated ASO titers and the detection of a site of entry for bacteria in patients with ADL supports a streptococcal etiology for this condition.

A preliminary study of filariasis related acute adenolymphangitis with special reference to precipitating factors and treatment modalities.

Episodic adenolymphangitis (ADL) is one of the important clinical manifestations of lymphatic filariasis. Recurrent ADLs contribute to the progress of the disease and also have important socioeconomic implications since they cause significant loss of man days. The present study was conducted in order to identify the precipitating factors responsible for ADL attacks and also to examine the different modalities of treatment. Sixty-five individuals with filariasis related ADL attacks, who are residents of Alleppey district (endemic for Brugia malayi) were studied. All efforts were taken to identify the precipitating factors for ADLs in these individuals. They were hospitalized for a period of five days or more. All of them received symptomatic antipyretic/antiinflammatory therapy and topical antibiotic/antifungal treatment of the affected limbs. They were then randomly allocated to one of the following four regimens: group I - symptomatic alone; group II - symptomatic plus antibiotics; group III - symptomatic followed by diethylcarbamazine citrate (DEC) and group IV - symptomatic plus antibiotic followed by DEC. Patients in groups III and IV received DEC every three months up to one year. There was a significant relationship between the number of ADL attacks and the grade of edema. Presence of focus of infection in the affected limb could be identified in 28 of the 65 patients. In the majority of patients (48) response to treatment was rapid (resolution in less than five days). Neither antibiotics nor DEC (given at intervals of three months) appeared to alter the frequency of ADL attacks. On the otherhand simple hygienic measures combined with good foot care and local antibiotic/antifungal cream application (where required), were effective in reducing the number of ADL attacks.

Ivermectin in the treatment of bancroftian filarial infection in Orissa, India.

Ivermectin treatment was evaluated for its efficacy and side reactions in sixty patients of Orissa with Bancroftian filarial infection and microfilaremia. Ivermectin was administered as a single oral dose at four dosage levels (20, 50, 100 and 200 micrograms/kg), and both microfilarial clearance and associated side reactions were monitored in a double blind fashion. Blood microfilariae were cleared in all patients at all dosages within 1 to 14 days. In most patients microfilariae reappeared by third month. The microfilaria appearance by third and sixth month averaged 12.2 to 44 percent of pretreatment values in the four study groups. Side reactions were encountered in almost all patients, the commonest being fever, headache, weakness, myalgia and cough which occurred most prominently 12 to 72 hours after treatment. Side reactions were more frequent and severe in patients with high microfilaria counts. Clinical reaction scores for each group were independent of the dose administered. The 200 micrograms dose group showed significantly more rapid microfilariae clearance and its delayed reappearance as compared with the other dosage groups and without inducing significantly greater clinical reaction scores.

Salivary cortisol in the assessment of adrenocortical function in patients with pulmonary tuberculosis.

Adrenocortical function was assessed on the basis of changes in salivary cortisol in patients with pulmonary tuberculosis and the findings compared with those in healthy subjects. A method of direct radioimmunoassay of salivary cortisol was standardized and the sensitivity was 0.8 nmol/l. Cortisol levels in saliva were significantly higher in the patients than in the healthy subjects (P less than 0.001). The diurnal rhythm of cortisol secretion was disturbed in the patients with a significant increase in salivary cortisol beyond 1800 h. While dexamethasone caused an appreciable suppression (87%), stimulation with ACTH (tetracosactrin) resulted in a marked increase in salivary cortisol, the increase being significantly higher in the healthy subjects than in the patients (P less than 0.001). Attempts to classify subjects as positive or negative responders to tetracosactrin based on increases in salivary cortisol in relation to plasma cortisol changes were however not successful, as the agreement between the two methods ranged from 73 to 80 per cent with various criteria used.