Bacillus Calmette-Guérin vaccine complications in Iranian children at a University Hospital.

BACKGROUND: Although the BCG vaccine remains the only available vaccine, a number of complications from local to systemic adverse reactions can occur. OBJECTIVE: The aim of the study was to review the clinical features and treatment of Bacillus Calmette-Guérin (BCG) complications in children. METHODS: Children with clinical and laboratory findings compatible with a diagnosis of local complication and disseminated disease at Masih Daneshvari Medical Center were enrolled from March 2013 to September 2015. RESULTS: Among 49 children with BCG complications, 35 (71%) had local complications and 14 (29%) had disseminated disease. The mean age at presentation was nine months (range: 1m-13y). The male to female ratio was 1.7:1. Suppurative lymphadenitis was seen in 25 of 35 (71%) cases. Among cases with disseminated disease, primary immunodeficiency (PID) was identified in nine (64%) cases. All cases with non-suppurative lymphadenitis were managed conservatively. Twenty (80%) cases with suppurative lymphadenitis were managed differently with medical treatment or surgery. In disseminated cases, three (43%) were treated with only medical treatment and eight (57%) with both medical and surgical treatment. CONCLUSIONS: Most children with BCG complications had a local disease in our study. A higher rate of disseminated disease was also observed. In addition, PID was identified in most children with disseminated disease. Development of more appropriate BCG vaccines and changing the current vaccination programme in cases with suspected PID are required in our country.

Pulmonary computed tomography scan findings in chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease is a phagocyte defect, characterised by recurrent infections in different organs due to a defect in NADPH oxidase complex. This study was performed to investigate pulmonary problems of CGD in a group of patients who underwent computed tomography (CT) scan. METHODS: Computed tomography scan was performed in 24 patients with CGD. The findings of the CT scan were documented in all of these patients. RESULTS: Areas of consolidation and scan formation were the most common findings, which were detected in 79% of the patients. Other abnormalities in order of frequencies were as follows: small pulmonary nodules (58%); mediastinal lymphadenopathy (38%); pleural thickening (25%); unilateral hilar lymphadenopathy (25%); axillary lymphadenopathy (21%); bronchiectasis (17%); abscess formation (17%); pulmonary large nodules or masses (8%); and free pleural effusion (8%). CONCLUSION: The pulmonary CT scans of the patients with CGD demonstrated a variety of respiratory abnormalities in the majority of the patients. While recurrent respiratory infections and abscesses are considered as prominent features of CGD, early diagnosis and precise check-up of the respiratory systems are needed to prevent further pulmonary complications.

IL-2-inducible T-cell kinase deficiency with pulmonary manifestations due to disseminated Epstein-Barr virus infection.

IL-2-inducible T-cell kinase (ITK) deficiency is a rare inherited immunodeficiency disease characterized by homozygous mutations in the ITK gene and the inability to control Epstein-Barr virus (EBV) infection leading to EBV-associated lymphoproliferative disorders of B cell origin. Many aspects of its clinical presentation and immunologic phenotype are still unclear to clinicians. We report on a 14-year-old female patient with complaints of an 8-month history of cough and fever. Imaging studies revealed diffuse pulmonary nodules and mediastinal lymphadenopathy. Transbronchial lung biopsy showed nonmalignant polyclonal B cell proliferation. High titers of EBV DNA were detected by PCR analysis in bronchoalveolar lavage fluid, bone marrow, and blood. Genomic analysis revealed a homozygous single base pair deletion in exon 5 of the ITK gene (c.468delT) in this patient. Treatment with rituximab (anti-CD20 mab) resulted in complete clinical remission with resolution of pulmonary lesions and a negative EBV titer in serum. All patients with EBV-associated lymphoproliferative disorders should be analyzed for mutations in ITK.

Demographics, laboratory parameters and outcomes of 1061 patients with coronavirus disease 2019: a report from Tehran, Iran.

We aimed to determine the characteristics of coronavirus disease 2019 (COVID-2019) among the Iranian population. In this study, we collected and analysed the demographics, laboratory findings and outcomes of patients with COVID-19 who were admitted to Masih Daneshvari Hospital in Tehran, Iran between 20 February 2020 and 2 April 2020. Among 1061 patients, 692 (65.2%) were male and the median age was 55 years (interquartile range (IQR), 44-66 years). Totally, 129 (12.2%) patients died during hospitalization in the ward or intensive care unit. From the remaining 932 individuals, 46 (5.0%) were admitted to the intensive care unit and 886 (95.0%) were hospitalized in the ward. Those patients who died were significantly older than those hospitalized in the ward (p < 0.001). The median absolute number of lymphocytes was 1.2 × 103/µL (IQR 0.9 × 103 to 1.6 × 103/µL) and 708 (66.7%) patients had lymphopenia (absolute lymphocyte count <1500/µL). Among the laboratory tests, D-dimer, serum ferritin and albumin had the strongest correlations with mortality (r = 0.455, r = 0.412, r = -0.406, respectively; p < 0.001 for each one). In conclusion, laboratory findings could provide useful information with regard to the management of individuals with COVID-19.

Frequency of isolated hepatitis B core antibody in HIV-hepatitis C virus co-infected individuals.

Association between isolated hepatitis B core antibody (anti-HBc) and hepatitis C virus (HCV) infection has been noted in HIV-infected individuals. This study describes the frequency of isolated anti-HBc and its possible value for the detection of HBV-DNA in HIV-infected patients with or without HCV co-infection. Ninety-two HIV-infected patients were enrolled in the study. Hepatitis B surface antigen (HBs Ag), anti-HBs, anti-HBc, anti-HCV, HIV viral load and CD4 count were tested in all subjects. Then we compared 63 subjects with HIV-HCV co-infection with 29 subjects with HIV infection alone regarding isolated anti-HBc (HBs Ag negative, anti-HBs negative and anti-HBc positive). The presence of HBV-DNA was determined by real-time polymerase chain reaction in serum samples of patients with isolated anti-HBc. Of 63 anti-HCV-positive patients, 18 subjects (28.6%, 95% [confidence interval] CI: 22.6-34.6%), and of 29 anti-HCV-negative patients, five subjects (17.2%, 95% CI: 11.5-22.9%) had isolated anti-HBc. HBV-DNA was detectable in three of 18 anti-HCV-positive patients (16.7%, 95% CI: 9.7-23.7%) and none of the anti-HCV-negative patients with isolated anti-HBc. Our study showed that individuals co-infected with HIV and HCV were more likely to have isolated anti-HBc than subjects with HIV alone. This investigation also demonstrates that the presence of isolated anti-HBc in HIV-HCV-infected individuals may reflect occult HBV infection in these patients.

Successful control of exacerbation of Allergic Bronchopulmonary Aspergillosis due to Aspergillus terreus in a cystic fibrosis patient with short-term adjunctive therapy with voriconazole: A case report.

A 12-year-old boy with cystic fibrosis (CF) and a history of glucocorticoid-dependent allergic bronchopulmonary aspergillosis (ABPA) was referred to our hospital. The ABPA was diagnosed when he was 8 years old and he had been treated with several course of oral glucocorticoids for recurrent exacerbations. He was readmitted when aged 12 with a history of worsening shortness of breath and chest tightness. A recurrence of ABPA was diagnosed based on eosinophilia and elevation of Aspergillusspecific IgE and IgG, and total IgE. Thoracic high-resolution computed tomography (HRCT) showed central bronchiectasis with parenchymal infiltrates. The treatment started with itraconazole and oral corticosteroid. After 2 months of treatment, he was re-admitted to the hospital due to a progressive worsening of respiratory symptoms. Chest HRCT revealed the a sub segmental atelectasis in the left lung. Microscopic examination of sputum and BAL samples demonstrated septate hyphae consistent with Aspergillus species. Sputum and BAL culture yielded Aspergillus ochraceus and Aspergillus terreus, which were both sensitive to itraconazole and voriconazole. The treatment was switched to voriconazole and the patient showed significant clinical, serological and mycological improvement after three months. This case shows that voriconazole may be used as an alternative for treatment of ABPA due to Aspergillus terreus.

Outcome of treatment of MDR-TB patients with standardised regimens, Iran, 2002-2006.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) imposes a formidable burden on national health systems. There is still no consensus on the subject, with controversies regarding treatment protocols, treatment outcomes and the various treatment regimens. METHODS: The present study describes Iran's second national cohort for treatment of MDR-TB. The study comprised all documented MDR-TB cases in Iran referred to our centre during the period 2002-2006. All patients received a standardised second-line regimen consisting of ofloxacin, cycloserine, prothionamide and amikacin. Based on drug susceptibility testing results, ethambutol and pyrazinamide were added to the regimen. RESULTS: Forty-three patients diagnosed with MDR-TB, with a mean age of 44.38 +/- 19.05 years, received treatment; of these, 27 (62.8%) were male. Twenty-three were (53.5%) Iranians and the remainder were Afghans. All patients were acquired MDR-TB cases. Of the 43 cases, 25 (58.1%) experienced severe clinically significant adverse effects; 29 (67.5%) had a successful outcome and 14 (32.5%) had a poor outcome (treatment failure in six [14%] and death in eight [18.6%]). Mortality was higher in Iranians (P = 0.039) and in patients whose initial regimen was changed due to adverse drug reactions (P = 0.01). CONCLUSION: Compared with previous studies, our study was able to obtain more favourable outcomes of MDR-TB treatment using a standardised regimen.

Clinical and laboratory profile of patients with tuberculosis/HIV coinfection at a national referral centre: a case series.

This case series describes the clinical and laboratory profile of 15 patients with tuberculosis (TB) HIV coinfection admitted to a referral centre in the Islamic Republic of Iran. Most of the patients (13) were male; the mean age was 36.9 years. Intravenous drug use was the route of transmission for all males and heterosexual intercourse for the 2 females; 12 patients had a history of imprisonment. All patients had pulmonary TB; 13 were smear-positive and all except 1 had atypical radiological presentation. Drug-induced hepatitis occurred in 3 patients and 12 had hepatitis C coinfection. Five patients died. The mean CD4 count was 229.2 (SD 199.5) cells/mm3 and 78.6% had CD4 count < 350. TB may be an AIDS-defining illness in this country.

Mycobacterium bovis infection in children in the same family: transmission through inhalation.

Two children in the same family were infected with Mycobacterium bovis ("M. bovis"). The molecular typing showed an identical source of infection. Although on school of thought was that the route of transmission was by ingestion of contaminated dairy milk, in other it was thought to be by air-borne transmission. The presentation highlighted the possibility of M. bovis infection in the pediatrics populations through aerosols.

Tuberculosis of the breast: report of 4 clinical cases and literature review.

Nearly 18% of tuberculosis (TB) cases have only extrapulmonary manifestations. Breast tuberculosis is a rare type of extrapulmonary TB. This paper reports 4 cases of breast TB confirmed either pathologically or mycobacteriologically or both. These reports showed that TB should always be considered first in the differential diagnosis of granulomatous mastitis in TB-endemic areas. Therapy included at least 6 months of anti-TB medication and surgery when indicated.

Impact of anti-tuberculosis therapy on plasma zinc status in childhood tuberculosis.

This study compared plasma zinc levels in 15 children with active pulmonary tuberculosis, 15 malnourished children and 15 healthy children. Mean plasma zinc concentrations in children with tuberculosis (71.7 microg/dL) were not significantly different than the other 2 groups (72.5 and 76.9 microg/dL). The zinc status of the children with tuberculosis was evaluated after 2 months and 4 months of DOTS therapy. The serum zinc level during anti-tuberculosis therapy decreased after 1 month and then recovered to the initial level after 4 months of treatment.

Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance.

Multidrug-resistant tuberculosis (MDR-TB), caused by drug-resistant strains of Mycobacterium tuberculosis, is an increasingly serious problem worldwide. Here we examined a data set of whole-genome sequences from 5,310 M. tuberculosis isolates from five continents. Despite the great diversity of these isolates with respect to geographical point of isolation, genetic background and drug resistance, the patterns for the emergence of drug resistance were conserved globally. We have identified harbinger mutations that often precede multidrug resistance. In particular, the katG mutation encoding p.Ser315Thr, which confers resistance to isoniazid, overwhelmingly arose before mutations that conferred rifampicin resistance across all of the lineages, geographical regions and time periods. Therefore, molecular diagnostics that include markers for rifampicin resistance alone will be insufficient to identify pre-MDR strains. Incorporating knowledge of polymorphisms that occur before the emergence of multidrug resistance, particularly katG p.Ser315Thr, into molecular diagnostics should enable targeted treatment of patients with pre-MDR-TB to prevent further development of MDR-TB.

Pulmonary mycobacterium Simiae infection and HTLV1 infection: an incidental co-infection or a predisposing factor?

There is little information on atypical mycobacterium and human T lymphotropic virus Type I (HTLV-I) co-infection. We present the first case of pulmonary M. simiae infection in co-infection with HTLV-1, confirmed by ELISA antibody test and Western Blot. We discuss the clinical characteristics and laboratory tests of the patient and presumptive immunological relation. We propose that in patients with the HTLV infection and pulmonary symptoms and signs compatible with tuberculosis, evaluation for atypical mycobacteriosis may be recommendable.

Primary and acquired drug resistance in childhood tuberculosis.

This study determined the resistance pattern of Mycobacterium tuberculosis to 4 first-line anti-tuberculosis drugs in children with pulmonary tuberculosis at the Iranian National Research Institute of Tuberculosis and Lung Diseases from 1999 to 2004. There were 350 children with positive cultures over the study period: 7 (2%) were resistant to at least one of the 4 anti-tuberculosis drugs. Primary resistance was detected in 4 cases and secondary resistance in 3 cases. Most cases (6) were among Afghan refugees. Resistance to rifampicin both in primary and secondary resistances was high, showing that children in the Islamic Republic of Iran face the threat of drug-resistant tuberculosis transmission.

Treatment monitoring and prevalence of drug resistance in tuberculosis patients in Tehran.

SETTING: Health care clinics and private practitioners in Tehran. OBJECTIVE: To analyse rates of drug resistance and response to treatment in tuberculosis patients. DESIGN: A prospective study of 257 patients undergoing treatment for whom data were collected on drug susceptibility testing and outcome as well as age, sex and history of treatment. RESULTS: Of 774 initially diagnosed patients, 380 were female and 394 were male; 520 (67%) of the cases had pulmonary disease. The overall rate of primary drug resistance among Mycobacterium tuberculosis isolates resistant to at least one drug was 87/563 (15.5%). Twenty-three patients were multidrug-resistant. Among 215 patients with drug-susceptible cultures recruited for follow-up, rapid response to short-course chemotherapy was observed in 190 (88%) who were successively both smear and culture negative after 2 and 4 months of treatment. After 6 months of treatment, 12 of the 25 patients with slow response to treatment had positive cultures; one was smear-positive. Of the 42 patients with drug-resistant isolates, satisfactory bacteriological response was observed after 6 months of treatment in 30 (71%). CONCLUSIONS: These observations support regional recommendations for short-course treatment regimens. Culture rather than smear result could be a key parameter for individually guiding the duration of treatment in patients with poor response to treatment.

Detection of Mycobacterium tuberculosis in bronchial washing of smear-positive patients after sputum conversion.

The main purpose of chemotherapy of tuberculosis is to ensure the noninfectiousness of patients with active pulmonary tuberculosis. For this reason, the sputum of smear-positive pulmonary tuberculosis patients is examined at the end of the first and second month of therapy to determine the conversion rate, which is expected to be 85% at the end of the second month. The patients whose sputum has converted to smear-negative are considered noninfectious. The aim of this study was to challenge the theory that negative sputum smear test results always indicate the absence of Mycobacterium tuberculosis bacilli in respiratory secretions from patients with active pulmonary tuberculosis after treatment. In order to achieve this goal, 46 patients with pulmonary tuberculosis whose sputum was positive for M. tuberculosis at the first visit were followed until they gave two consecutive negative smears. The bronchoalveolar lavage fluid of these patients was then examined for M. tuberculosis bacilli. It was observed that eight (17.5%) and five (10%) of these patients, who had already undergone sputum conversion, gave positive smear and culture results respectively. It could be concluded that a negative sputum result is not an appropriate index for evaluating the infectiousness of patients with pulmonary tuberculosis, and, since a few Mycobacterium tuberculosis bacilli can cause tuberculosis, especially in an immunocompromised host, it is mandatory that complementary studies to assess the transmission and virulence of Mycobacterium tuberculosis bacilli after sputum conversion be conducted.

Primary multi-drug resistant tuberculosis presented as lymphadenitis in a patient without HIV infection.

Primary multi-drug resistant extrapulmonary tuberculosis is an uncommon form of the disease, but it seems that by increasing the number drug resistant tuberculosis around the world, the number of cases of primary multi-drug resistant tuberculosis with extrapulmonary presentation also is going to rise. In this report, we describe a 19-year old, HIV negative man with primary multi-drug resistant TB lymphadenitis, presented with cervical lymphadenopathy and sinus discharge at the site of involved lymph nodes. The Acid Fast Bacilli (AFB) smear of sputum was negative but the AFB smear of discharged fluid as well as the excisional biopsy of the lymph nodes confirmed the M. tuberculosis infection. The patient underwent the treatment with a combination of isoniazide, clofazimine, pyrazinamide, ofloxacin and amikacin with promising results. By increasing the number of drug resistant tuberculosis patients around the world, appropriate diagnosis and treatment of different presentations of the disease need a special attention.

Reasons for delay in the management of patients with pulmonary tuberculosis.

The study assessed reasons for delay between patient's first symptoms of tuberculosis and initiation of therapy. Fifty newly diagnosed cases of pulmonary tuberculosis admitted to the NRITLD in Teheran were studied. Mean patient delay before consulting a physician was 12.5 +/- 10 days, significantly higher among men than women. Mean delay until the physicians' diagnosis was 93 +/- 80 days, significantly higher for women than for men. Almost no treatment delay was observed (mean 4 +/- 4 days after diagnosis had been confirmed). The major delay was the time taken by physicians to diagnose tuberculosis in symptomatic patients. An active and effective national tuberculosis programme is needed in the Islamic Republic of Iran, with integration of the programme in medical school curricula and in continuing professional training.