Studies from developed countries have reported on host-related risk factors for extra-pulmonary tuberculosis (EPTB). However, similar studies from high-burden countries like Nepal are lacking. Therefore, we carried out this study to compare demographic, life-style and clinical characteristics between EPTB and PTB patients.
A retrospective analysis was carried out on 474 Tuberculosis (TB) patients diagnosed in a tertiary care hospital in western Nepal. Characteristics of demography, life-style and clinical features were obtained from medical case records. Risk factors for being an EPTB patient relative to a PTB patient were identified using logistic regression analysis.
The age distribution of the TB patients had a bimodal distribution. The male to female ratio for PTB was 2.29. EPTB was more common at younger ages (< 25 years) and in females. Common sites for EPTB were lymph nodes (42.6%) and peritoneum and/or intestines (14.8%). By logistic regression analysis, age less than 25 years (OR 2.11 95% CI 1.12–3.68) and female gender (OR 1.69, 95% CI 1.12–2.56) were associated with EPTB. Smoking, use of immunosuppressive drugs/steroids, diabetes and past history of TB were more likely to be associated with PTB.
Results suggest that younger age and female gender may be independent risk factors for EPTB in a high-burden country like Nepal. TB control programmes may target young and female populations for EPTB case-finding. Further studies are necessary in other high-burden countries to confirm our findings.
HIV/AIDS pandemic is responsible for the resurgence of TB worldwide, resulting in increased morbidity and mortality. HIV and Mycobacterium tuberculosis have a synergistic interaction; each propagates progression of the other. Coinfection with HIV infection leads to difficulties in both the diagnosis and treatment of tuberculosis, increase risk of death, treatment failure and relapse.
The aim of the present study is to study the clinical, radiological profile of pulmonary and extrapulmonary tuberculosis (EPTB) in HIV-seropositive patients and their relationship to CD4 counts.
Materials and Methods:
It was a prospective study conducted over a period of 1 year in the department of medicine, Indira Gandhi Medical College, Shimla. We examined 87 HIV-infected patients with associated tuberculosis recruited from the department of medicine and antiretroviral center and were subjected to thorough clinical examination, X-ray chest, tuberculin testing and sputum examination for AFB and necessary relevant investigations for EPTB.
Most common affected age group was 31-40 years. EPTB is the commonest form of TB in our study detected in 65 patients. Commonest EPTB was CNS tuberculosis. Disseminated tuberculosis was only found in patient with CD4 count less than 200/cmm. Majority of lymph node TB was diagnosed by fine needle aspiration cytology (FNAC) examination. All patients with AFB-positive lymph node had CD4 count below 200/cum.
The results of this study provide information regarding the various forms of TB and their presentation in HIV-infected persons. Early diagnosis of tuberculosis and prompt institution of antitubercular treatment (ATT) reduces mortality and morbidity significantly. In resource-poor areas, the diagnosis can be established with cytological/biochemical analysis of fluid, histopathological examination and ZN staining of tissue coupled with radiological features and response to ATT. Therefore, adequate knowledge of the manifestations of tuberculosis in HIV-infected patients is absolutely necessary for optimal management and to reduce mortality and morbidity.
AFB smear; CD4 count; extrapulmonary; HIV; pulmonary; tuberculosis
Extrapulmonary tuberculosis (EPTB) has an increasing rate in Turkey. The reason remains largely unknown. A better understanding of the demographic and microbial characteristics of EPTB in the Turkish population would extend the knowledgebase of EPTB and allow us to develop better strategies to control tuberculosis (TB).
We retrospectively evaluated clinical and laboratory data of 397 bacteriologically-confirmed TB cases diagnosed during an eight year-period using by chi-square analysis and multivariate logistic regression model.
Of the 397 study patients, 103 (25.9%) had EPTB and 294 (74.1%) had pulmonary tuberculosis (PTB). The most commonly seen two types of EPTB were genitourinary TB (27.2%) and meningeal TB (19.4%). TB in bone/joints, pleural cavity, lymph nodes, skin, and peritoneal cavity occurred at a frequency ranging from 9.7% to 10.7%. The age distribution was significantly different (P < 0.01) between PTB and EPTB, with patients older than 45 years tending to have an increased risk of EPTB. Furthermore, the distribution of different types of EPTB differed significantly among age groups (P = 0.03). Meningeal and bone and/or joint TB were more commonly observed among the male patients, while lymphatic, genitourinary, and peritoneal TB cases were more frequently seen among females. Unique strain infection was statistically significantly associated with EPTB (OR: 2.82, 95% CI [1.59, 5.00])
EPTB accounted for a significant proportion of TB cases in Malatya, Turkey between 2001 and 2007. The current study has provided an insight into the dynamics of EPTB in Malatya, Turkey. However, the risk factors for having EPTB in Malatya, Turkey remain to be assessed in future studies using population-based or randomly selected sample.
The aim of this study is to assess the value of chest radiographs (CXRs) and sputum examinations in detecting pulmonary involvement of tuberculosis (TB) in patients with extra-pulmonary tuberculosis (EPTB).
Materials and Methods:
A retrospective analysis was performed among 248 EPTB patients with culture-proven diagnosis of tuberculosis seen between January 2001 and December 2007 at a tertiary teaching hospital, Riyadh, Saudi Arabia. Demographics, clinical, laboratory and radiological findings were reviewed and assessed. This study was approved by the hospital ethics and research committee.
One hundred twenty five of 233 EPTB patients (53.6%) had abnormal CXR findings. There was a significant difference in the occurrence of positive sputum culture results between patients with abnormal CXR findings (30/57) and those with normal CXR findings (4/17) (P = 0.04). Of 17 HIV-negative/unknown HIV-status EPTB patients with normal CXR results, 4 patients (23.5%) had positive sputum culture results. Intrathoracic lymphadenopathy (P < 0.001), pleural TB (P < 0. 001) and disseminated TB (P = 0.004) were associated with an increased risk of abnormal CXR findings. Patients with cough (52.9%), weight loss (41.2%) and night sweats (26.5%) are more likely to have positive sputum culture results.
CXR findings are predictive of positive sputum culture results. However, the rate of normal CXR among EPTB patients with positive sputum culture results was relatively high. Therefore, respiratory specimen cultures should be obtained in TB suspects with a normal CXR to identify potentially infectious cases of TB.
Predictors; pulmonary; extra-pulmonary tuberculosis; radiology
Factors related to the development of extrapulmonary forms of tuberculosis (EPTB) are still poorly understood, particularly in high-endemic countries like Brazil. The objective of the paper is to determine host and Mycobacterium tuberculosis (MTB) strain-related factors associated with the development of EPTB in Espírito Santo state, Brazil.
Methods and Findings
We conducted a retrospective laboratory-based surveillance study of new tuberculosis (TB) cases diagnosed in Espírito Santo state, Brazil between 1998 and 2007. We genotyped 612 isolates of MTB from 606 TB patients using spoligotyping and IS6110-restriction fragment length polymorphism (RFLP) typing and compared sociodemographic and clinical characteristics of patients with pulmonary TB (PTB) and EPTB. Among 606 patients, 464 (77%) had PTB, 79 (13%) had EPTB, 51 (8%) had both, and 12 (2%) had miliary TB. The IS6110 RFLP analysis demonstrated that 250 (41%) isolates belonged to clustered RFLP patterns, 27 (11%) of which were from EPTB. We identified 73 clusters including 35 (48%) composed of 2 isolates each. By spoligotyping, 506 (83%) MTB isolates fell into known patterns and 106 (17%) fell into patterns with no family assignment; 297 (48%) isolates belonged to the Latin-American Mediterranean family. Higher school level (4-7 years OR: 0.16 95% CI 0.34-0.73 and > 8 years of education, OR 0.06 95% CI 0.009-0.50) white ethnicity (OR: 2.54 95% CI 1.03-6.25) and HIV infection (OR: 16.83 95% CI 5.23-54.18) were associated with EPTB. No specific strain lineage or percentage of clustering was associated with EPTB.
These results demonstrate that risk factors for EPTB are related more to host than to MTB strain lineage characteristics.
Background: Tuberculosis remains a major global public health problem and an on-going epidemic. Though the chief objectives of the Revised National Tuberculosis Control Programme (RNTCP) in detecting and curing the infectious pulmonary cases is well taken, there has been a steady rise in the number of Extra Pulmonary Tuberculosis (EPTB) cases as documented in several studies. EPTB which usually constitutes around 15%-20% of the total TB cases is now being increasingly reported due to a combination of better diagnostic facilities, and the HIV pandemic. Though several studies have shown increasing prevalence of EPTB, only few studies are available, especially in the Indian scenario, that study the pattern and risk factors. Hence, this retrospective observational study was undertaken to determine the sites of the involvement, HIV co-infection and usefulness of various diagnostic modalities in EPTB affecting patients attending a medical college DOTS clinic.
Material and Methods: One hundred ten EPTB patients referred to the DOTS clinics of the TB & Chest department from the period Dec 2010– Mar 2012 were included in the study. The diagnosis of EPTB was established by combined clinical, microbiological, histopathological &/or imaging modalities. Their medical records were assessed to determine the age distribution, gender and anatomical sites of involvement. The presence of co-morbid conditions like smoking history, alcoholism, diabetic and HIV status were noted. BCG status and Mantoux test readings were recorded. The different diagnostic tests used in confirming EPTB at different sites were recorded. Chest x-ray was analysed for all patients to assess coexisting pulmonary involvement. All patients were followed to assess the outcome of treatment.
Results: The mean age of patients was 34.4. The male to female ratio was 58:52 showing a slight male predominance. The most common site of involvement was lymph node followed by pleural effusion and abdominal TB. The prevalence of lymph node TB was noted to be higher in female patients as compared to other sites of EPTB. Mantoux test was positive in 57 (51.8%) patients. HIV co-infection was noted in only 3 (2.7%) patients. Concomitant pulmonary involvement was seen in 19 (17.3%) patients.
Conclusions: Lymph node was the most common site involvement showing a significant female preponderance followed by pleural effusion and abdominal TB. The rates of HIV co-infection and diabetes mellitus were 2.7% and 20% respectively. The most useful diagnostic modality was tissue sampling followed by imaging. Mantoux test is not unequivocal for the diagnosis of EPTB.
Extra–Pulmonary Tuberculosis; DOTS clinic; TB Lymphadenopathy; HIV co-infection; Mantoux test
The HIV epidemic has posed major, almost insurmountable, challenges to tuberculosis control efforts across the world. This study analyzes the prevalence and disease profile of HIV/AIDS coinfection in Vadodara, Gujarat, India.
Materials and Methods:
This study was conducted in the HIV Referral Clinic at Vadodara, India. Using convenience sampling method, 246 HIV-positive patients coinfected with tuberculosis were enrolled. A detailed history of every case was taken followed by a thorough physical examination. Baseline and follow up laboratory and radiological investigations were carried out as appropriately warranted.
Out of 500 HIV positive patients who presented to the clinic during the study period, 246 (49.2%) were coinfected with tuberculosis. Out of 246 coinfected cases, 35(14.2%) presented with demonstrable and documented tuberculosis whereas in 211(85.8%) cases, tuberculosis was extemporaneously detected by actively screening the patients. Sixty nine percent of patients were males, while 10.5% of cases were below fifteen years of age. The majority (68%) of patients had manifestations of extrapulmonary tuberculosis; but pulmonary tuberculosis, which is a more common presentation in HIV-negative cases, was present in only fifty five percent of this segment of the population. Abdominal tuberculosis was the most common site (74%) amongst extrapulmonary tuberculosis involvement, followed by clinically palpable lymph nodes (22%) and pleural effusion (17%).
The prevalence of tuberculosis in HIV-positive patients in this study (49%) was substantially higher than that reported in previous studies. However, this could be attributed to a selection and/or a diagnosis bias. This study used abdominal ultrasound for the diagnosis of tuberculosis which might have obviously increased the prevalence. Moreover, these cases were not confirmed by biopsy or other definitive TB diagnostic methods.
Coinfection; HIV; HIV/AIDS; India; TB; tuberculosis
Antananarivo, the capital city of Madagascar, has an endemic focus of tuberculosis (TB). We specifically studied patients with extrapulmonary TB (EPTB) and grouped patients according to infected body site. The strains were characterized by IS6110 fingerprinting and compared with those isolated from patients with pulmonary TB (PTB) during the same period in order to determine the possible association between the genotype and the clinical expression of TB. A total of 316 TB patients were included in this study: 151 individuals with EPTB, 10 with both PTB and EPTB, and 155 with PTB alone. Pleural TB was the major EPTB localization (77%) and was found more often in older patients, while PTB or EPTB in which the localization was other than pleural (other EPTB) was found in younger patients. The male-to-female ratio was slightly higher in pleural TB patients (3.06:1) than in patients with other EPTB (1.35:1). There was no significant difference in the BCG status among patients with PTB, pleural TB, and other EPTB. Analysis of IS6110 patterns showed that 167 patients (52.8%) were assigned to 37 clusters of 2 to 34 patients. Analysis of the IS6110 clusters and the IS6110 families did not show any association with a particular clinical expression of the disease. Patients with PTB or other EPTB were more likely to have strains with one IS6110 copy than patients with pleural TB. The clustering rate was found to be significantly higher in female patients (62%) than in male patients (48%) (P = 0.029), suggesting that Malagasy women were more likely to progress to disease after infection than men.
Background: Tuberculosis (TB) is an important disease in human immunodeficiency virus (HIV) infected children living in regions where TB is endemic. There are limited data on the outcome of culture confirmed TB in HIV infected children.
Aims and Methods: To describe the outcome on TB therapy and overall mortality in HIV infected children with culture confirmed TB through a retrospective cohort study.
Results: Eighty seven children, median age 24 months, contributed to 93 TB episodes; six children had two confirmed episodes. Pulmonary disease (PTB) was present in 71 episodes (76.3%), extrapulmonary disease (EPTB) in 43 (46.2%), and of these, both PTB and EPTB were present in 21 (22.6%). There was cure based on bacteriological and/or radiological criteria in 54 episodes (58.1%). Eighteen children died during TB therapy and there were a total of 34 deaths (39.1%). In univariate analysis (n = 87 patients), severe malnutrition, age ⩽1 year, and a negative tuberculin skin test were significant risk factors for death during TB therapy. In multivariate survival analysis (n = 87 patients), HIV disease category, severe malnutrition at diagnosis, and lack of cure at the end of TB therapy were significantly associated with overall mortality.
Conclusion: In the absence of antiretroviral therapy, HIV infected children with confirmed TB have poor outcomes on antituberculosis therapy and are at high risk of death during and after completion of antituberculosis therapy, especially due to non-TB related causes. There is an urgent need to optimise and monitor antituberculosis therapy in HIV infected children and to improve access to TB and other preventative therapy.
This article describes the clinical, epidemiologic, laboratory, and treatment characteristics of pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) in Eastern North Carolina, a primarily rural area. The database was obtained for 1988-1992 from the University Medical Center of Eastern North Carolina-Pitt County and East Carolina University School of Medicine (the tertiary care referral center for this region). One hundred thirty-eight culture-positive patients were enrolled in the study; 56% were PTB and 44% were EPTB. African-American males constituted 59% of the population. Sixty-nine percent of the patient base were uninsured. There was a bimodal age distribution of < 40 and > 60 years of age. Factors associated with PTB (reported as odds ratios) were white males (2.5), diabetes mellitus (5.4), and cancer (5.1). Factors associated with EPTB (reported as odds ratios) were African-American females, positive human immunodeficiency virus (HIV) serology (8.7), low hematocrit (32.6), and elevated alkaline phosphatase (199). This study emphasizes that in the latest resurgence of tuberculosis, impoverished rural areas, which have been ignored in earlier and present control efforts, are important reservoirs of disease.
Little is known about the treatment of multidrug-resistant tuberculosis (MDR-TB) in HIV-co-infected adolescents. This study aimed to present the intermediate outcomes of HIV-infected adolescents aged 10–19 years receiving second-line anti-TB treatment in a Médecins Sans Frontières (MSF) project in Mumbai, India.
A retrospective review of medical records of 11 adolescents enrolled between July 2007 and January 2013 was undertaken. Patients were initiated on either empirical or individualized second-line ambulatory anti-TB treatment under direct observation.
The median age was 16 (IQR 14–18) years and 54% were female. Five (46%) adolescents had pulmonary TB (PTB), two (18%) extrapulmonary disease (EPTB) and four (36%) had both. Median CD4 count at the time of MDR-TB diagnosis was 162.7 cells/µl (IQR: 84.8–250.5). By January 2013, eight patients had final and 3 had interim outcomes. Favourable results were seen in four (36.5%) patients: one was cured and three were still on treatment with negative culture results. Seven patients (64%) had poor outcomes: four (36.5%) died and three (27%) defaulted. Three of the patients who died never started on antiretroviral and/or TB treatment and one died 16 days after treatment initiation. Two of the defaulted died soon after default. All patients (100%) on-treatment experienced adverse events (AEs): two required permanent discontinuation of the culprit drug and two were hospitalized due to AEs. No patient required permanent discontinuation of the entire second-line TB or antiretroviral regimens.
Early mortality and mortality after default were the most common reasons for poor outcomes in this study. Early mortality suggests the need for rapid diagnosis and prompt treatment initiation, and adolescents might benefit from active contact-tracing and immediate referral. Default occurred at different times, suggesting the need for continuous, intensified and individualized psychosocial support for co-infected adolescents. Operational research among co-infected adolescents will be especially important in designing effective interventions for this vulnerable group.
The site of extrapulmonary tuberculosis infection has a known effect on mortality. Authors use a large clinical case series to identify previously unconfirmed risk factors that are associated with site of extrapulmonary tuberculosis infection.
Background. In the United States, the proportion of patients with extrapulmonary tuberculosis (EPTB) has increased relative to cases of pulmonary tuberculosis. Patients with central nervous system (CNS)/meningeal and disseminated EPTB and those with human immunodeficiency virus (HIV)/AIDS have increased mortality. The purpose of our study was to determine risk factors associated with particular types of EPTB.
Methods. We retrospectively reviewed 320 cases of EPTB from 1995–2007 at a single urban US public hospital. Medical records were reviewed to determine site of EPTB and patient demographic and clinical characteristics. Multivariable logistic regression analyses were performed to determine independent associations between patient characteristics and site of disease.
Results. Patients were predominantly male (67%), African American (82%), and US-born (76%). Mean age was 40 years (range 18–89). The most common sites of EPTB were lymphatic (28%), disseminated (23%), and CNS/meningeal (22%) disease. One hundred fifty-four (48.1%) were HIV-infected, 40% had concomitant pulmonary tuberculosis, and 14.7% died within 12 months of EPTB diagnosis. Multivariable analysis demonstrated that HIV-infected patients were less likely to have pleural (adjusted odds ratio [AOR] 0.3; 95% confidence interval [CI] .2, .6) as site of EPTB disease than HIV-uninfected patients. Among patients with EPTB and HIV-infection, patients with CD4 lymphocyte cell count <100 were more likely to have severe forms of EPTB (CNS/meningeal and/or disseminated) (AOR 1.6; 95% CI, 1.0, 2.4).
Conclusions. Among patients hospitalized with EPTB, patients coinfected with HIV and low CD4 counts were more likely to have CNS/meningeal and disseminated disease. Care for similar patients should include consideration of these forms of EPTB since they carry a high risk of death.
Background and aim
Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome is a major public health issue in Africa. The objective of this study was to determine which of isolated HIV-infection, isolated naive pulmonary tuberculosis (PTB), or naive HIV-PTB coinfection was more harmful to inflammatory, hepatic, and renal functions.
This cross-sectional study was undertaken among ten patients with isolated HIV infection, ten patients with isolated naive HIV infection, ten patients with isolated PTB and 32 patients with HIV-PTB coinfection, with the aim of determining which group had the highest levels of oxidative stress and hepatic and renal dysfunction markers. Serum aminotransferase (AST), alanine transferase (ALT), gamma-glutamyl transferase (GGT), and creatinine measurements were compared across the three groups of patients, who were managed from admission in the pulmonology division of the Brazzaville Teaching Hospital, Congo.
HIV patients had the highest levels of ALT, GGT, and creatinine before and after adjusting for age and sex. Adjusted levels of AST, ALT, GGT, and creatinine were higher in HIV-PTB coinfection patients than in sero-negative PTB patients.
There is a significant association between HIV infection and increase in concentration of ALT, GGT, and creatinine.
Africa; tuberculosis; HIV-tuberculosis coinfection; renal function
Background & objectives:
Mycobacterial heparin-binding haemagglutinin adhesin (HBHA) plays an important role in humoral and cellular immune response and is a potential diagnostic tool for tuberculosis (TB) serodiagnosis. This study was carried out to assess the usefulness of HBHA in TB clinics for differential diagnosis of pulmonary and extra-pulmonary TB (PTB, EPTB).
In this study, 165 outpatients and 133 healthy volunteers were included to investigate the role of HBHA in TB diagnosis including the serodiagnostic tests and the interferon-γ release assays (IGRAs). The healthy volunteers were all without BCG vaccination including 73 subjects with purified protein derivative (PPD) (-) and 60 ones with PPD (+) (that is P-B- and P+B-). Of all the 165 outpatients 77 were PTB and 88 were EPTB. HBHA protein was used for serodiagnostic tests and IGRAs in peripheral blood mononuclear cells.
HBHA-specific antibody levels in the serum of healthy subjects were significantly different from the patients with PTB or EPTB (P<0.05). HBHA specific antibody levels in PTB patients could differentiate from EPTB with limited sensitivity (77.08%; 95%CI, 62.69 to 87.97%) and specificity (87.50%; 95%CI, 74.75 to 95.27%). IFN-γ levels in the healthy (P+B- and P-B-) groups were significantly different (P<0.01) with a detection sensitivity of 84.8% (95%CI, 68.54 to 93.02%) and specificity of 80.7% (95%CI, 65.22 to 92.62%). The PTB and EPTB subjects showed no difference in IFN-γ production.
Interpretation & conclusions:
HBHA serodiagnostic test with IGRAs had the limited potential for use as auxiliary tools for the differential diagnosis of PTB and EPTB, since both methods showed low sensitivity and specificity.
Binding haemagglutinin; differential diagnosis; heparin; interferon-γ level; serodiagnostic test; tuberculosis
Ultrasound can rapidly identify abnormal signs, which in high prevalence settings, are highly suggestive of extra-pulmonary tuberculosis (EPTB). Unfortunately experienced sonographers are often scarce in these settings.
A protocol for focused assessment with sonography for HIV-associated tuberculosis (FASH) which can be used by physicians who are relatively inexperienced in ultrasound was developed.
The technique as well as normal and pathological findings are described and the diagnostic and possible therapeutic reasoning explained. The protocol is intended for settings where the prevalence of HIV/TB co-infected patients is high.
FASH is suitable for more rapid identification of EPTB even at the peripheral hospital level where other imaging modalities are scarce and most of the HIV and TB care will be delivered in the future.
HIV; TB; Co-infection; Ultrasound; Focused assessment; Resource-limited setting.
The proportion of extrapulmonary tuberculosis (EPTB) reported in the United States has been gradually increasing. HIV infection and foreign birth are increasingly associated with tuberculosis and understanding their effect on the clinical presentation of tuberculosis is important.
Case-control study of 6,124 persons with tuberculosis reported to the North Carolina Division of Public health from January 1, 1993 to December 31, 2006. Multivariate logistic regression was used to obtain adjusted odds ratios measuring the associations of foreign birth region and US born race/ethnicity, by HIV status, with EPTB.
Among all patients with tuberculosis, 1,366 (22.3%) had EPTB, 563 (9.2%) were HIV co-infected, and 1,299 (21.2%) were foreign born. Among HIV negative patients, EPTB was associated with being foreign born (adjusted ORs 1.36 to 5.09, depending on region of birth) and with being US born, Black/African American (OR 1.84; 95% CI 1.42, 2.39). Among HIV infected patients, EPTB was associated with being US born, Black/African American (OR 2.60; 95% CI 1.83, 3.71) and with foreign birth in the Americas (OR 5.12; 95% CI 2.84, 9.23).
Foreign born tuberculosis cases were more likely to have EPTB than US born tuberculosis cases, even in the absence of HIV infection. Increasing proportions of foreign born and HIV-attributable tuberculosis cases in the United States will likely result in a sustained burden of EPTB. Further research is needed to explore why the occurrence and type of EPTB differs by region of birth and whether host genetic and/or bacterial variation can explain these differences in EPTB.
Direct smear examination with Ziehl-Neelsen (ZN) staining for the diagnosis of pulmonary tuberculosis (PTB) is cheap and easy to use, but its low sensitivity is a major drawback, particularly in HIV seropositive patients. As such, new tools for laboratory diagnosis are urgently needed to improve the case detection rate, especially in regions with a high prevalence of TB and HIV.
To evaluate the performance of two in house PCR (Polymerase Chain Reaction): PCR dot-blot methodology (PCR dot-blot) and PCR agarose gel electrophoresis (PCR-AG) for the diagnosis of Pulmonary Tuberculosis (PTB) in HIV seropositive and HIV seronegative patients.
A prospective study was conducted (from May 2003 to May 2004) in a TB/HIV reference hospital. Sputum specimens from 277 PTB suspects were tested by Acid Fast Bacilli (AFB) smear, Culture and in house PCR assays (PCR dot-blot and PCR-AG) and their performances evaluated. Positive cultures combined with the definition of clinical pulmonary TB were employed as the gold standard.
The overall prevalence of PTB was 46% (128/277); in HIV+, prevalence was 54.0% (40/74). The sensitivity and specificity of PCR dot-blot were 74% (CI 95%; 66.1%-81.2%) and 85% (CI 95%; 78.8%-90.3%); and of PCR-AG were 43% (CI 95%; 34.5%-51.6%) and 76% (CI 95%; 69.2%-82.8%), respectively. For HIV seropositive and HIV seronegative samples, sensitivities of PCR dot-blot (72% vs 75%; p = 0.46) and PCR-AG (42% vs 43%; p = 0.54) were similar. Among HIV seronegative patients and PTB suspects, ROC analysis presented the following values for the AFB smear (0.837), Culture (0.926), PCR dot-blot (0.801) and PCR-AG (0.599). In HIV seropositive patients, these area values were (0.713), (0.900), (0.789) and (0.595), respectively.
Results of this study demonstrate that the in house PCR dot blot may be an improvement for ruling out PTB diagnosis in PTB suspects assisted at hospitals with a high prevalence of TB/HIV.
HIV, HBVand HCV is major public health concerns. Because of shared routes of transmission, HIV-HCV coinfection and HIV-HBV coinfection are common. HIV-positive individuals are at risk of coinfection with HBV and HCV infections. The prevalence rates of coinfection with HBV and HCV in HIV-patients have been variable worldwide depending on the geographic regions, and the type of exposure.
This study aimed to examine HBV and HCV coinfection serologically and determine the shared and significant factors in the coinfection of HIV-positive patients.
This descriptive, cross-sectional study was carried out on 391 HIV-positive patients including 358 males and 33 females in Lorestan province, west Iran, to survey coinfection with HBsAg and anti-HCV. The retrospective demographic data of the subjects was collected and the patients' serums were analyzed by ELISA kits including HBsAg and anti-HCV. The collected data was analyzed with SPSS software (15) and Chi-square. Fisher's exact test with 5% error intervals was used to measure the correlation of variables and infection rates.
The results of the study indicated that the prevalence of coinfection in HIV-positive patients with hepatitis viruses was 94.4% (370 in 391), out of whom 57 (14.5%) cases were HBsAg positive, 282 (72%) cases were anti-HCV positive, and 31 (7.9%) cases were both HBsAg and anti-HCV positive.
There was a significant correlation between coinfection with HCV and HBV and/or both among HIV-positive patients depending on different variables including sex, age, occupation, marital status, exposure to risk factors.(p < 0.001).
Entecavir (ETV) was developed for the treatment of chronic hepatitis B virus (HBV) infection and is globally approved for that indication. Initial preclinical studies indicated that ETV had no significant activity against human immunodeficiency virus type 1 (HIV-1) in cultured cell lines at physiologically relevant ETV concentrations, using traditional anti-HIV assays. In response to recent clinical observations of anti-HIV activity of ETV in HIV/HBV-coinfected patients not receiving highly active antiretroviral therapy (HAART), additional investigative studies were conducted to expand upon earlier results. An extended panel of HIV-1 laboratory and clinical strains and cell types was tested against ETV, along with a comparison of assay methodologies and resistance profiling. These latest studies confirmed that ETV has only weak activity against HIV, using established assay systems. However, a >100-fold enhancement of antiviral activity (equivalent to the antiviral activity of lamivudine) could be obtained when assay conditions were modified to reduce the initial viral challenge. Also, the selection of a M184I virus variant during the passage of HIV-1 at high concentrations of ETV confirmed that ETV can exert inhibitory pressure on the virus. These findings may have a significant impact on how future assays are performed with compounds to be used in patients infected with HIV. These results support the recommendation that ETV therapy should be administered in concert with HAART for HIV/HBV-coinfected patients.
Objective. To assess the radiographic features in patients with Human Immunodeficiency Virus (HIV) complicated by pulmonary tuberculosis (PTB), and the association with CD4 lymphocyte count and sputum smear. Method. A prospective study was carried out on 89 HIV positive patients with PTB. The demographics, smoking history, sputum smear result, chest radiographic findings and CD4 lymphocyte count were documented. Results. Out of the 89 patients recruited in the study, 41 were males and 48 were females. Eighteen (18) patients had typical radiographic features, 60 patients had atypical radiographic features while only 11 of them had normal radiographic films. Sixty eight (68) patients had CD4 count <200 cells/mm3, 19 patients had CD4 count between 200–499 cells/mm3, while only 2 patients had CD4 count from 500 cells/mm3 upwards. The association between low CD4 count and radiographic finding was statistically significant, (P value <0.05). Sixty (60) patients had negative sputum smear for Acid and Alcohol Fast Bacilli (AAFB), while the remaining 29 patients had positive smear. The association between low CD4 count and negative smear was statistically significant (P value <0.05). Conclusion. The radiographic pattern and the result of the sputum smear for AAFB has a significant relationship and association with the immune status of patients with Human Immunodeficiency Virus (HIV) complicated by pulmonary tuberculosis.
Introduction: Extra-Pulmonary Tuberculosis (EPTB) accounts for approximately 40% of the tuberculosis cases. Though it is not communicable, it is a significant cause of morbidity. This study was conducted to know the efficacy of the Polymerase Chain Reaction (PCR) as an additional tool, along with the conventional methods, in the diagnosis of EPTB.
Material and Methods: Clinical samples were collected from suspected cases of EPTB. The Ziehl-Neelsen staining (ZNS), culture on the Lowenstein-Jensen medium (LJM) and PCR testing with the use of a commercial kit were performed on the homogenized samples.
Results: A total of 182 samples which were received for the molecular diagnosis of EPTB were also tested by ZNS and culture on LJM for the presence of Mycobacterium tuberculosis. Of these, 22 were positive by at least one of the tests which were used. PCR detected the maximum number of cases of EPTB, followed by culture. The results of PCR and the conventional tests were analyzed by using McNemar’s test for the correlated proportions-the exact method of ‘IBM SPSS Statistics 20’. The analysis showed a statistical significance.
Conclusions: Whenever they are feasible, using all the available tests in combination increases the laboratory detection rates of M. tuberculosis from clinical samples. PCR must be included in the diagnostic panel of EPTB.
Tuberculosis; Extrapulmonary tuberculosis; PCR; Mycobacterium
Tuberculosis remains a major public health problem globally, with India being one of the high burden countries. The common causative agent is Mycobacterium tuberculosis but in developing countries M. bovis is reported as a potential human pathogen. Almost 20% of all reported cases of tuberculosis are of extra pulmonary form of disease. Diagnosis of extra pulmonary tuberculosis (EPTB) is not always possible with conventional methods, due to the long time required and the paucibacillary nature of samples; hence the need of rapid molecular methods. A prospective study was conducted on 300 patients of EPTB over a period of 5 years. These patients were suspected cases of tubercular meningitis, tubercular ascites and tubercular lymphadenitis. Samples analyzed were cerebrospinal fluid, ascitic fluid and lymph node fine needle aspirate. A two step PCR targeting hup B gene was used. Clinical response to anti tubercular therapy (ATT) was taken as positive (gold standard). PCR for hup B gene was positive in 147 samples out of 155 ATT responders. Of these 85.71% were infected with M. tuberculosis, 9.52% with M. bovis alone and 4.76% showed co infection with both M.tb and M. bovis. The sensitivity and specificity of PCR was 90.32 and 94.48% respectively.
Mycobacterium tuberculosis; Mycobacterium bovis; hup B gene; Extra pulmonary tuberculosis
BACKGROUND: Kaposi's sarcoma is the most common secondary neoplasm to complicate HIV infection and may cause pulmonary disease. METHODS: A prospective study was carried out in 140 consecutive patients who were HIV seropositive and required bronchoscopy for new respiratory symptoms of at least two weeks' duration, with either a chest radiographic abnormality or abnormality of pulmonary function. The patients were classified into those with single local endobronchial lesions of Kaposi's sarcoma or generalised widespread lesions. Before bronchoscopy all patients had routine simple pulmonary function tests and chest radiography. RESULTS: Thirty nine (21%) patients had evidence of cutaneous Kaposi's sarcoma. Nineteen of the 39 were found to have endobronchial Kaposi's sarcoma lesions at bronchoscopy, but none of those who did not have cutaneous Kaposi's sarcoma. Respiratory symptoms of cough and breathlessness and radiographic abnormalities were attributed to Kaposi's sarcoma in this group, except in four patients who had concomitant pneumocystis pneumonia. Eight patients had local endobronchial Kaposi's sarcoma lesions and 11 had extensive lesions. Patients with extensive lesions had more widespread radiographic abnormalities; four of the patients with local endobronchial lesions had normal chest radiographs. All patients had reduced transfer factor for carbon monoxide and transfer coefficient, whereas patients with extensive endobronchial lesions also had reductions in forced expiratory volume in one second and forced vital capacity. Median survival (with palliative chemotherapy with vincristine and bleomycin) was only seven months. In three patients who needed further diagnostic bronchoscopy endobronchial lesions had regressed while they were having chemotherapy. CONCLUSIONS: This study suggests that endobronchial Kaposi's sarcoma is a relatively common finding in patients with AIDS and is particularly common in patients with cutaneous Kaposi's sarcoma who present with respiratory illness. Endobronchial Kaposi's sarcoma causes respiratory disease and abnormalities of pulmonary function. Pulmonary Kaposi's sarcoma should be considered as a possible cause for respiratory illness in any patient with cutaneous Kaposi's sarcoma.
Background: While smear positive patients with tuberculosis (TB) are considered more infectious than smear negative patients, the latter can also transmit TB.
Methods: In a molecular epidemiology study of 791 patients in the Greater Vancouver regional district, the number of episodes of TB transmission from two groups of smear negative clustered patients by RFLP (assumed to be involved in recent transmission) was estimated after assessing for potential bias. Group 1 (n = 79) included patients with pulmonary TB or pulmonary + extrapulmonary disease (PTB or PTB+EPTB); group 2 (n = 129) included all patients in group 1 + extrapulmonary cases alone.
Results: In the total sample the mean (SD) age was 51 (21) years, 54.3% were male, and 17.0% of patients were clustered. Compared with smear negative patients, smear positive patients were more likely to be in a cluster (OR = 2.0, 95% CI 1.1 to 3.6) and to have had a history of ethanol abuse (OR = 2.7, 95% CI 1.0 to 6.7), diabetes mellitus (OR = 2.8, 95% CI 1.1 to 7.0), injection drug use (OR = 3.1, 95% CI 1.1 to 8.3), and to have had a previous hospital admission (OR = 8.5, 95% CI 5.1 to 14.0). The proportion of episodes of transmission from smear negative clustered patients ranged from 17.3% to 22.2% in group 1 and from 25% to 41% in group 2.
Conclusion: In Greater Vancouver, smear negative cases appear responsible for at least one sixth of culture positive episodes of TB transmission.
We communicate the diagnosis by microscopy of a pulmonary coinfection produced by Cryptococcus neoformans and Pneumocystis jiroveci, from a respiratory secretion obtained by bronchoalveolar lavage of an AIDS patient. Our review of literature identified this coinfection as unusual presentation. Opportunistic infections associated with HIV infection are increasingly recognized. It may occur at an early stage of HIV-infection. Whereas concurrent opportunistic infections may occur, coexisting Pneumocystis jiroveci pneumonia (PCP) and disseminated cryptococcosis with cryptococcal pneumonia is uncommon. The lungs of individuals infected with HIV are often affected by opportunistic infections and tumours and over two-thirds of patients have at least one respiratory episode during the course of their disease. Pneumonia is the leading HIV-associated infection. We present the case of a man who presented dual Pneumocystis jiroveci and cryptococcal pneumonia in a patient with HIV. Definitive diagnosis of PCP and Cryptococcus requires demonstration of these organisms in pulmonary tissues or fluid. In patients with < 200/microliter CD4-lymphocytes, a bronchoalveolar lavage should be performed. This patient was successfully treated with amphotericin B and trimethoprim sulfamethoxazole. After 1 week the patient showed clinical and radiologic improvement and was discharged 3 weeks later.
Cryptococcus neoformans; Pneumocystis jiroveci; Pulmonary coinfection; Diagnosis test; Opportunistic pathogen; Pneumonia; Definitive diagnosis