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Clinical Predictors and Accuracy of Empiric Tuberculosis Treatment among Sputum Smear-Negative HIV-Infected Adult TB Suspects in Uganda  [PDF]
Lydia Nakiyingi, John Mark Bwanika, Bruce Kirenga, Damalie Nakanjako, Catherine Katabira, Gloria Lubega, Joseph Sempa, Barnabas Nyesiga, Heidi Albert, Yukari C. Manabe
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0074023
Abstract: Introduction The existing diagnostic algorithms for sputum smear-negative tuberculosis (TB) are complicated, time-consuming, and often difficult to implement. The decision to initiate TB treatment in resource-limited countries is often largely based on clinical predictors. We sought to determine the clinical predictors and accuracy of empiric TB treatment initiation in HIV-infected sputum smear-negative TB suspects using sputum culture as a reference standard. Setting Out-patient HIV-TB integrated urban clinic in Kampala, Uganda. Methods HIV-infected TB suspects were screened using sputum smear microscopy, and mycobacterial sputum liquid and solid cultures were performed. Smear results were made available to the clinician who made a clinical decision on empiric TB treatment initiation for sputum smear-negative patients. Clinic records were reviewed for patients whose sputum smears were negative to collect data on socio-demographics, TB symptomatology, chest X-ray findings, CD4 cell counts and TB treatment initiation. Results Of 253 smear-negative TB suspects, 56% (142/253) were females, median age 38 IQR (31–44) years, with a median CD4 cell count of 291 IQR (150–482) cells/mm3. Of the 85 (33.6%) smear-negative patients empirically initiated on TB treatment, 35.3% (n = 30) were sputum culture positive compared to only 18 (10.7%) of the 168 untreated patients (p<0.001). Abnormal chest X-ray [aOR 10.18, 95% CI (3.14–33.00), p<0.001] and advanced HIV clinical stage [aOR 3.92, 95% CI (1.20–12.85), p = 0.024] were significantly associated with empiric TB treatment initiation. The sensitivity and specificity of empiric TB treatment initiation in the diagnosis of TB in HIV-infected patients after negative smear microscopy was 62.5% and 73.7% respectively. Conclusion In resource-limited settings, clinically advanced HIV and abnormal chest X-ray significantly predict a clinical decision to empirically initiate TB treatment in smear-negative HIV-infected patients. Empiric TB treatment initiation correlates poorly with TB cultures. Affordable, accurate and rapid point-of-care diagnostics are needed in resource-limited settings to more accurately determine which HIV-infected TB suspects have smear-negative TB.
Prevalence of Non-Tuberculous Mycobacterial Infections among Tuberculosis Suspects in Nigeria  [PDF]
Gambo Aliyu, Samer S. El-Kamary, Alash’le Abimiku, Clayton Brown, Kathleen Tracy, Laura Hungerford, William Blattner
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0063170
Abstract: Background Nigeria is ranked in the top five countries for tuberculosis deaths worldwide. This study investigated the mycobacterial agents associated with presumptive clinical pulmonary tuberculosis (TB) in Nigeria and evaluated the pattern and frequency of mycobacterial infections over twelve calendar months period. Methods Sputum samples from 1,603 consecutive new cases with presumptive diagnosis of TB were collected from August 2010 to July 2011. All sputum samples were incubated for detection of mycobacterial growth and those with positive acid fast bacilli (AFB) growth were tested to detect mycobacterium tuberculosis (MTB) complex and characterized to differentiate between MTB complex species. Cultures suggestive of Non-tuberculous mycobacterial infections (NTM) were sub-cultured and characterized. Results Of the 1,603 patients screened, 444 (28%) culture-positive cases of pulmonary tuberculosis were identified. Of these, 375 (85%) were due to strains of MTB complex (354 cases of M. tuberculosis, 20 M. africanum and one case of M. bovis) and 69 (15%) were due to infection with NTM. In contrast to the MTB complex cases, the NTM cases were more likely to have been diagnosed during the calendar months of the Harmattan dust season (OR = 2.34, 1.28–4.29; p = 0.01), and aged older than 35 years (OR = 2.77, 1.52–5.02, p = 0.0007), but less likely to have AFB identified on their sputum smear (OR = 0.06, 0.02–0.14, p<0.0001). Among those with NTM infection, cases 35 years or younger were more likely to have co-infection with HIV (3.76, 1.72–8.22; p = 0.0009) compared to those older than 35 years. Interpretation The high proportion of younger patients with clinical pulmonary TB due to NTM and co-infection with HIV and the likely role of the seasonal dust exposure in the occurrence of the disease, present novel public health challenges for prevention and treatment.
Operational Implementation of LED Fluorescence Microscopy in Screening Tuberculosis Suspects in an Urban HIV Clinic in Uganda  [PDF]
Heidi Albert, Lydia Nakiyingi, Joseph Sempa, Olive Mbabazi, Sheena Mukkada, Barnabas Nyesiga, Mark D. Perkins, Yukari C. Manabe
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0072556
Abstract: Background Light emitting diode (LED) fluorescence microscopy (FM) is an affordable, technology targeted for use in resource-limited settings and recommended for widespread roll-out by the World Health Organization (WHO). We sought to compare the operational performance of three LED FM methods compared to light microscopy in a cohort of HIV-positive tuberculosis (TB) suspects at an urban clinic in a high TB burden country. Methods Two spot specimens collected from TB suspects were included in the study. Smears were stained using auramine O method and read after blinding by three LED-based FM methods by trained laboratory technicians in the Infectious Diseases Institutelaboratory. Leftover portions of the refrigerated sputum specimens were transported to the FIND Tuberculosis Research Laboratory for Ziehl Neelsen (ZN) smear preparation and reading by experienced technologist as well as liquid and solid culture. Results 174 of 627 (27.8%) specimens collected yielded one or more positive mycobacterial cultures. 94.3% (164/174) were M. tuberculosis complex. LED FM was between 7.3–11.0% more sensitive compared to ZN microscopy. Of the 592 specimens examined by all microscopy methods, there was no significant difference in sensitivity between the three LED FM methods. The specificity of the LED FM methods was between 6.1% and 7.7% lower than ZN microscopy (P<0.001), although exclusion of the single poor reader resulted in over 98% specificity for all FM methods. Conclusions Laboratory technicians in routine settings can be trained to use FM which is more sensitive than ZN microscopy. Despite rigorous proficiency testing, there were operator-dependent accuracy issues which highlight the critical need for intensive quality assurance procedures during LED FM implementation. The low sensitivity of FM for HIV-positive individuals particularly those with low CD4 T cell counts, will limit the number of additional patients found by LED FM in countries with high rates of HIV co-infection.
Factors associated with pastoral community knowledge and occurrence of mycobacterial infections in Human-Animal Interface areas of Nakasongola and Mubende districts, Uganda
Clovice Kankya, Adrian Muwonge, Susan Olet, Musso Munyeme, Demelash Biffa, John Opuda-Asibo, Eystein Skjerve, James Oloya
BMC Public Health , 2010, DOI: 10.1186/1471-2458-10-471
Abstract: Two hundred and fifty three (253) individuals were subjected to a questionnaire survey across the study districts of Nakasongola and Mubende. Data were analyzed using descriptive statistics and multivariable logistic regression analysis.Humans sharing of the water sources with wild animals from the forest compared to savannah ecosystem (OR = 3.3), the tribe of herding pastoral community (OR = 7.9), number of rooms present in household (3-5 vs. 1-2 rooms) (OR = 3.3) were the socio-demographic factors that influenced the level of knowledge on mycobacterial infections among the pastoral communities. Tribe (OR = 6.4), use of spring vs. stream water for domestic use (OR = 4.5), presence of sediments in household water receptacle (OR = 2.32), non separation of water containers for drinking and domestic use (OR = 2.46), sharing of drinking water sources with wild animals (OR = 2.1), duration of involvement of >5 yrs in cattle keeping (OR = 3.7) and distance of household to animal night shelters (>20 meters) (OR = 3.8) were significant socio-demographic factors associated with the risk of occurrence of mycobacterioses among the pastoral communities in Uganda.The socio-demographic, environmental and household related factors influence the risk of occurrence as well as pastoralists' knowledge of mycobacterial infections in the pastoral households at the human-environment-livestock/wildlife pastoral interface areas of Uganda.Nontuberculous mycobacteria (NTM) are emerging opportunistic pathogens whose role in human and animal disease is increasingly being recognized [1,2]. In the last few decades, the incidence of classical tuberculosis (TB) in man has been on the increase alongside tuberculosis-like disease caused by NTMs [3]. Currently, the major concern is their increasing role as opportunistic pathogens in HIV/AIDS infections and potent immunosuppressive therapies [4]. The apparent increase in the frequency of isolation of NTM's from clinical specimens and the mounting evid
Aetiology of Pulmonary Symptoms in HIV-Infected Smear Negative Recurrent PTB Suspects in Kampala, Uganda: A Cross-Sectional Study  [PDF]
Alphonse Okwera, Freddie Bwanga, Irene Najjingo, Yusuf Mulumba, David K. Mafigiri, Christopher C. Whalen, Moses L. Joloba
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0082257
Abstract: Introduction Previously treated TB patients with pulmonary symptoms are often considered recurrent TB suspects in the resource-limited settings, where investigations are limited to microscopy and chest x-ray. Category II anti-TB drugs may be inappropriate and may expose patients to pill burden, drug toxicities and drug-drug interactions. Objective To determine the causes of pulmonary symptoms in HIV-infected smear negative recurrent pulmonary tuberculosis suspects at Mulago Hospital, Kampala. Methods Between March 2008 and December 2011, induced sputum samples of 178 consented HIV-infected smear negative recurrent TB suspects in Kampala were subjected to MGIT and LJ cultures for mycobacteria at TB Reference Laboratory, Kampala. Processed sputum samples were also tested by PCR to detect 18S rRNA gene of P.jirovecii and cultured for other bacteria. Results Bacteria, M. tuberculosis and Pneumocystis jirovecii were detected in 27%, 18% and 6.7% of patients respectively and 53.4% of the specimens had no microorganisms. S. pneumoniae, M. catarrhalis and H. influenzae were 100% susceptible to chloramphenicol and erythromycin but co-trimoxazole resistant. Conclusion At least 81.5% of participants had no microbiologically-confirmed TB. However our findings call for thorough investigation of HIV-infected smear negative recurrent TB suspects to guide cost effective treatment.
Incremental Yield of Serial Sputum Cultures for Diagnosis of Tuberculosis among HIV Infected Smear Negative Pulmonary TB Suspects in Kampala, Uganda  [PDF]
Willy Ssengooba, Noah Kiwanuka, David P. Kateete, Achilles Katamba, Moses L. Joloba
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0037650
Abstract: Background Sputum culture is the gold standard for diagnosis of pulmonary tuberculosis (PTB). Although mostly used for research, culture is recommended by the World Health Organization for TB diagnosis among HIV infected smear negative PTB suspects. Even then, the number of sputum samples required remains unspecified. Here, we determined the Incremental Yield (IY) and number of samples required to diagnose an additional PTB case upon second and third serial sputum culture. Methods/Findings This was a cross sectional study done between January and March 2011. Serial sputum samples were provided by participants within two days and cultured using Lowenstein Jensen (LJ) and Mycobacteria Growth Indicator Tube (MGIT) methods. A PTB case was defined as a positive culture on either one or both methods. The IY from the second and third serial cultures was determined and the reciprocal of the product of the fractions of IY provided the number of samples required for an additional PTB case. Of the 170 smear negative PTB suspects, 62 (36.5%) met the case definition. The IY of the second sample culture was 12.7%, 23.6% and 12.6% and for the third sample culture was 6.8%, 7.5% and 7.3% with LJ, MGIT and LJ or MGIT, respectively. The number of samples required for an additional PTB case and 95% CI upon the second sample culture were 29.9 (16.6, 156.5), 11.3 (7.6, 21.9) and 20.8 (12.5, 62.7); while for the third sample culture were 55.6 (26.4, 500.4), 35.7 (19.0, 313.8) and 36.1 (19.1, 330.9) by LJ, MGIT and LJ or MGIT respectively. Conclusions/Significance Among HIV infected smear negative PTB suspects in Kampala, 93% of PTB cases are diagnosed upon the second serial sputum culture. The number of cultures needed to diagnose an additional PTB case, ranges from 11–30 and 35–56 by the second and third sputum samples, respectively.
Investigation Outcomes of Tuberculosis Suspects in the Health Centers of Addis Ababa, Ethiopia  [PDF]
Amare Deribew,Nebiyu Negussu,Zenebe Melaku,Kebede Deribe
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018614
Abstract: Little is known about the prevalence of tuberculosis (TB) and HIV among TB suspects in primary health care units in Ethiopia.
The anti-mycobacterial activity of Lantana camara a plant traditionally used to treat symptoms of tuberculosis in South-western Uganda
C Kirimuhuzya, P Waako, M Joloba, O Odyek
African Health Sciences , 2009,
Abstract: Introduction: Tuberculosis continues to be a devastating public health problem. Many communities in Uganda use medicinal plants to treat various infections, including respiratory tract infections. There are claims that some can treat tuberculosis. Verifying some of these claims could lead to discovery of lead compounds for development of a TB drug. Methods: Chloroform and methanol extracts of L. camara collected from South-western Uganda were screened against three strains of Mycobacterium tuberculosis using the agar-well diffusion method. H37Rv, the rifampicin-resistant TMC-331 and a non-resistant wild strain (28-25271). The MIC and MBC were determined using the Agar dilution method on Middle brook 7H11. Results: The methanol extract showed the highest activity against all the three strains used, with zones of inhibition of 18.0-22.5 mm and MIC values of 20 μg/ml for H37Rv and 15 μg/ml for both TMC-331 and wild stain. The values for rifampicin were 1.0 μg/ml for both H37Rv and wild strain but rifampicin hardly showed any activity on TMC-331. The MBC value for the methanol extract of L. camara was 30μg/ml for the H37Rv, and 20μg/ml for both the TMC-331 and wild strains of M. tuberculosis. The MBC for rifampicin was 2.0μg/ml for both H37Rv and the wild strain. Conclusion: We conclude that L. camara contains principles active against M. tuberculosis, which merit further research.
An Early Morning Sputum Sample Is Necessary for the Diagnosis of Pulmonary Tuberculosis, Even with More Sensitive Techniques: A Prospective Cohort Study among Adolescent TB-Suspects in Uganda  [PDF]
Willy Ssengooba,David P. Kateete,Anne Wajja,Eric Bugumirwa,Gerald Mboowa,Carolyn Namaganda,Germine Nakayita,Maria Nassolo,Francis Mumbowa,Benon B. Asiimwe,James Waako,Suzanne Verver,Philippa Musoke,Harriet Mayanja-Kizza,Moses L. Joloba
Tuberculosis Research and Treatment , 2012, DOI: 10.1155/2012/970203
Abstract: The World Health Organization (WHO) recommends collection of two sputum samples for tuberculosis (TB) diagnosis, with at least one being an early morning (EM) using smear microscopy. It remains unclear whether this is necessary even when sputum culture is employed. Here, we determined the diagnostic yield from spot and the incremental yield from the EM sputum sample cultures among TB-suspected adolescents from rural Uganda. Sputum samples (both spot and early-morning) from 1862 adolescents were cultured by the Lowenstein-Jensen (LJ) and Mycobacterium Growth Indicator Tube (MGIT) methods. For spot samples, the diagnostic yields for TB were 19.0% and 57.1% with LJ and MGIT, respectively, whereas the incremental yields (not totals) of the early-morning sample were 9.5% and 42.9% ( ) with LJ and MGIT, respectively. Among TB-suspected adolescents in rural Uganda, the EM sputum culture has a high incremental diagnostic yield. Therefore, EM sputum in addition to spot sample culture is necessary for improved TB case detection. 1. Background Tuberculosis (TB) remains a global emergency, causing high mortality and morbidity particularly in sub-Saharan Africa [1]. Some studies have shown that the incidence of TB in adolescents (12–18 years old) has increased by 22% compared with a 38% decrease in children less than 5 years old [2]. Although there is scant data on TB in adolescents in Uganda and worldwide in general, their protective response against Mycobacterium tuberculosis (MTB) infection seems to be less effective [3]. Adolescents also have unique clinical presentations for TB; they are more asymptomatic and are more likely to have cavitary disease [4]. Reports indicate that many adolescents with active TB are diagnosed during late stage of the disease [2]. Additionally, the demographic and clinical characteristics of adolescents with TB differ from adults and children [5]. Furthermore, it is quite difficult to obtain quality sputum samples, which makes TB diagnosis among adolescents challenging. Indeed, many adolescents with TB are prone to producing smear negative sputum samples [6]. The World Health organization (WHO) and the International Union Against Tuberculosis and Lung Diseases (IUATLD) recommended collection of two sputum samples for smear microscopy with at least one being an early-morning (EM) sample. This aimed at reducing the workload per serial sample examined [7, 8]. However, these recommendations seem to work in settings serving the general population where external quality assurance (EQA) methods are well established. As such, those
Factors Affecting Aflatoxin Contamination of Harvested Maize in the Three Agroecological Zones of Uganda  [PDF]
A.N. Kaaya,W. Kyamuhangire,S. Kyamanywa
Journal of Applied Sciences , 2006,
Abstract: A survey was conducted in 2003 to establish aflatoxin levels in maize and the associated farmer practices in the three agroecological zones of Uganda. Maize kernels obtained from farmers in the Mid-Altitude (moist) zone had the highest aflatoxin contaminated samples (83%) and mean aflatoxin levels of 9.7 ppb followed by those from the Mid-Altitude (dry) where 70% were contaminated with a mean of 7.7 ppb, while the kernels sampled from the Highland zone had the least contaminated samples (55%) and mean aflatoxin levels of 3.9 ppb. Aflatoxin contamination in maize grain was positively related to leaving maize to dry in the field for more than three weeks, drying maize without husks, drying maize on bare ground, shelling maize by beating, heaping maize on the floor during storage and use of baskets for storage of maize. The practices that negatively impacted on aflatoxin development in maize in the agroecological zones were sorting before storage, storage of maize in shelled form, storage of maize in bags, use of improved granary as storage structures, storage of maize above fireplace and use of synthetic pesticides. Thus, those practices that reduce aflatoxin contamination of maize should be adopted by all farmers in Uganda to reduce the health hazards associated with consumption of contaminated maize grain.
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