High early death rate in tuberculosis patients in Malawi.

SETTING: Thirty-eight district and mission hospitals in Malawi. OBJECTIVES: In patients registered with all types of tuberculosis (TB) in 1997 to determine 1) treatment outcomes, and 2) when in the course of anti-tuberculosis treatment TB deaths occurred. DESIGN: A retrospective study using information from TB registers, health centre registers, TB treatment cards and TB ward admission books. RESULTS: A total of 16,004 patients were registered with all types of TB, 6471 with smear-positive pulmonary tuberculosis (PTB), 5305 with smear-negative PTB and 4228 with extra-pulmonary tuberculosis (EPTB). Of patients with all types of TB, 3720 (23%) died: death rates were 22% in smear-positive PTB, 26% in smear-negative PTB and 22% in EPTB. Month of death was known in 3371 patients (91% of those who died) and day of death in 3326 patients (89% of those who died). In patients who died, 19% of deaths occurred by day 7 and 41% by the end of the first month of treatment. A higher proportion of early deaths occurred in patients with smear-negative PTB and EPTB and in relation to increasing age. CONCLUSIONS: There was a high overall death rate in TB patients registered in 1997, with 40% of deaths occurring in the first month of treatment. Strategies to combat this problem are needed.     

Patient and health system delays in the diagnosis and treatment of tuberculosis in Southern Taiwan.

SETTING: Tainan city, Tainan county and 13 townships of Kaohsiung county, Southern Taiwan. OBJECTIVE: To measure delays in the diagnosis and treatment of sputum-positive tuberculosis (TB) and to determine factors associated with delays in seeking health care (patient delay) and in starting anti-tuberculosis treatment (health system delay). DESIGN: A population-based patient interview study. RESULTS: Median patient delay was 7 days (range 0-730). Median health system delay was 23 days (range 0-489), 13 for smear-positive patients and 37 for smear-negative patients (P < 0.005). Median total delay was 44 days (range 0-730). Age <65 years was associated with longer patient delay. Negative smear, absence of haemoptysis, not having a chest radiograph at the first medical consultation and visiting clinics for first consultation were associated with a longer health system delay. Age <65 years, negative smear and cough as the only presenting symptom were associated with longer total delay. CONCLUSION: Patient delay was substantially shorter than health system delay. To reduce health system delay, clinics need to be involved and the referral mechanism must be strengthened. Physicians should maintain high alert for TB and perform prompt sputum smear examinations.     

Patient and health system delays in the diagnosis of tuberculosis in Southern Thailand after health care reform.

SETTING: Seven public hospitals in a southern province of Thailand. OBJECTIVES: To measure delays in tuberculosis (TB) diagnosis and to examine the factors associated with these delays, with special focus on the effect of drug store utilisation and health insurance coverage on patient delay. DESIGN: A total of 202 newly diagnosed smear-positive and smear-negative pulmonary TB patients were interviewed using a structured questionnaire. RESULTS: The median patient, health system and total delay were 4.4, 2.8 and 9.4 weeks, respectively. Risk factors for patient delay were age 31-60 years, having mild illness, previous similar symptoms and first presenting to non-qualified providers. Health insurance was not associated with a shorter patient delay. Health system delay was significant longer for patients with health insurance and first presenting to low-level public health facility (i.e., community hospital, health centre, primary care unit or private clinic/hospital). CONCLUSIONS: The public should be informed how to recognise TB symptoms to shorten patient delay. The Thai National Tuberculosis Control Programme needs to supervise the private health sector, including drug stores, for better TB control. Drug store personnel need to be trained to recognise and refer TB suspects. The capacity of low-level public health facilities and private doctors in TB diagnosis needs improvement. A proper referral system should be developed.     

Patient and health care system delays in the diagnosis and treatment of tuberculosis.

SETTING: All culture-positive tuberculosis patients without previous treatment for tuberculosis (n = 184), New York City, April 1994. OBJECTIVE: To examine factors associated with delays in presenting to a health care provider (patient delay) and in starting antituberculosis treatment (health care system delay). DESIGN: Retrospective medical record review and patient interviews. RESULTS: Median total delay was 57 days (range 4-764), 35 for acid-fast bacilli smear-positive patients and 79 for smear-negative patients (P < 0.001). Median patient delay was 25 (range 0-731). Median health care system delay was 15 days, 6 for smear-positive patients and 31 for smear-negative patients (P < 0.001). In logistic regression, age 55-64 years (adjusted odds ratio [OR(adj)] 10.6, 95% confidence interval [CI] 1.3-86.9), and primary language other than English (OR(adj) 2.5, 95%CI 1.0-5.8), were associated with longer patient delays. Homelessness (OR(adj) 7.1, 95%CI 1.05-33.5), not having a chest radiograph at the first medical visit (OR(adj) 2.4, 95%CI 1.0-5.4), negative smear (OR(adj) 10.2, 95%CI 4.4-23.3) and absence of cough (OR(adj) 2.9, 95%CI 1.2-6.8) were associated with longer health care system delays. CONCLUSION: To reduce delays, patients should be educated to seek care more quickly, and should be provided with culturally appropriate health care and language services. Physicians should maintain a high index of suspicion for tuberculosis and perform appropriate diagnostic tests.     

Evaluation of a unified treatment regimen for all new cases of tuberculosis using guardian-based supervision.

SETTING: Ntcheu District, Malawi, using an oral antituberculosis treatment regimen. OBJECTIVE: To determine whether directly observed treatment (DOT) during the initial phase of treatment supervised either in hospital, at health centres or by guardians in the community, was associated with 1) satisfactory 2-month and 8-month treatment outcomes, and 2) with a reduction of in-patient hospital-bed days. DESIGN: Prospective data collection of all tuberculosis (TB) patients registered between 1 April 1996 and 30 June 1997, with 2-month and 8-month treatment outcomes, sputum smear conversion in smear-positive pulmonary TB patients (PTB) and in-patient hospital-bed days. RESULTS: Among the 600 new patients, 302 had smear-positive PTB, 150 smear-negative PTB and 148 extrapulmonary TB (EPTB). Eight-month treatment completion was 65% for smear-positive PTB patients, which was significantly higher than in patients with smear-negative PTB (45%) and EPTB (54%), due mainly to high 8-month mortality rates. The site of the intensive phase was determined in 596 patients: 178 (30%) received DOT from guardians, 115 (19%) from a health centre and 303 (51%) in hospital. At 2 months, mortality rates were significantly higher in hospitalised patients. Two-month treatment outcomes (including sputum smear conversion rates in smear-positive PTB patients) were similar between patients receiving DOT at health centres or from guardians. Decentralised DOT resulted in a 25% reduction in hospital-bed days in patients alive at 2 months compared with that predicted using the old regimens. CONCLUSION: Decentralising DOT to health centres and to guardians during the intensive phase is associated with satisfactory treatment outcomes.     

Extra-pulmonary tuberculosis at a regional hospital in Thailand

The purpose of this study was to analyze the cases of extra-pulmonary tuberculosis (EPTB) at Maharat Nakhon Ratchasima Hospital, a tertiary care regional hospital in Northeast Thailand. There were 398 cases of EPTB (46.9%) and 450 cases of pulmonary tuberculosis (PTB) (53.1%). The mean age of EPTB patients (47.58 years) was lower than that of PTB patients (51.6 years) (p < 0.01). Human Immunodeficiency Virus (HIV) seropositivity was found in 50 cases of EPTB (12.6%) and 55 cases of PTB (12.2%) which was not significantly different. The common sites of extra-pulmonary involvement were the lymph nodes (29.7%), followed by the pleura (27.4%), the bones and spine (25.1%), the meninges and brain (4.5%), the pericardium (3.5%) and the gastrointestinal tract (3.0%). Disseminated TB occurred in only 8 cases (2.0%). HIV seropositivity rates were more common in disseminated TB (OR 41.51, 95% CI 4.98-34.5), TB of the meninges and brain (OR 4.47, 95% CI 1.57-12.6) and TB of the lymph nodes (OR 3.49, 95% CI 1.86-6.54) and were less common in TB of the bones and spine (OR 0.05, 95% CI 0.01-0.37) and TB of the pleura (OR 0.24, 95%CI 0.09-0.63).     

Diagnosing smear-negative tuberculosis using case definitions and treatment response in HIV-infected adults.

OBJECTIVE: To assess the diagnostic utility of expanded case definitions for HIV-associated smear-negative pulmonary tuberculosis (PTB) and extra-pulmonary TB (EPTB), and to derive objective criteria for response to anti-tuberculosis treatment. DESIGN: A prospective cohort study of HIV-infected adults who met expanded clinical case definitions for smear-negative PTB and EPTB. METHODS: All participants were started on rifampicin-based anti-tuberculosis treatment after mycobacterial cultures from multiple sites. At weeks 2, 4 and 8, response to treatment (RTT) was assessed by measuring changes in weight, haemoglobin, C-reactive protein, Karnofsky performance score and symptom count ratio. RESULTS: Of 147 participants enrolled, 105 (71%) were diagnosed with definite (culture-positive) or probable (histological features) TB and 25 (17%) with possible TB (treatment response). The positive predictive value for the most common case definitions ranged from 89% to 96%. Significant improvements in all the RTT parameters occurred in the subjects with confirmed TB (P < 0.001). Clinically relevant RTT criteria were derived, two or more of which were met at week 8 in 97.5% of subjects with confirmed TB, 91.3% of subjects with possible TB and none of the subjects without TB. CONCLUSION: Expanded case definitions could enhance the diagnosis of PTB and EPTB in HIV-infected adults in resource-limited settings. Using objective criteria, RTT can be assessed within 8 weeks of initiating anti-tuberculosis treatment.     

Delay in the treatment of pulmonary TB in a changing demographic scenario.

OBJECTIVE: To quantify patient and health care delays in the treatment of pulmonary tuberculosis (PTB) in Emilia-Romagna region, Italy, and to study the association between migration status and delay. DESIGN: All patients with symptomatic PTB, aged >15 years, who were notified in Emilia-Romagna during 2003 and were alive at time of data collection, were included. An individual form was completed for each notified patient by the local health authority officer in charge of surveillance data. RESULTS: Median patient delay, health care delay and total delay were 7, 36 and 65 days, respectively. Recent migrants (stay in Italy < or = 3 years) had the longest patient delay (16 days), while Italian patients had the longest health care delay (60 days). Migration status was independently associated with both patient and health care delay, although the direction of association changed according to which delay was considered. CONCLUSION: Public health interventions aiming to reduce delay in treatment of PTB should improve the access of recent migrants to health care and increase suspicion of TB among Italian patients. Studies on delays in treatment of TB should investigate patient delay and health care delay as distinct outcomes.     

Recurrent tuberculosis: definitions and treatment regimens.

Within the National Tuberculosis Control Programme of Malawi, misunderstandings sometimes occur about the diagnosis and management of recurrent tuberculosis (TB). Patients with smear-positive pulmonary tuberculosis (PTB) who have had a previous, treated episode of smear-negative TB may be registered as 'new cases' rather than relapse cases, and thus denied the benefits of a retreatment regimen. Patients with a recurrent episode of smear-negative PTB or extra-pulmonary TB (EPTB) may also be wrongly registered as 'new cases' rather than recurrent cases. International guidelines about the treatment of recurrent smear-negative PTB and EPTB are not explicit, resulting in confusion about how best to manage these cases. It is suggested that all such cases be considered for re-treatment regimen because of concerns about acquired drug resistance. WHO and IUATLD guidelines on the diagnosis and management of recurrent and relapse TB need to be improved, and operational research studies should be conducted to provide answers to some outstanding questions.     

Childhood tuberculosis in Malawi: nationwide case-finding and treatment outcomes.

SETTING: All 43 non-private hospitals (three central, 22 [corrected] district and 18 [corrected] mission) in Malawi that register and treat adult and paediatric TB cases. OBJECTIVE: To assess the rate, pattern and treatment outcome of childhood TB case notifications in Malawi in 1998. DESIGN: Retrospective data collection using TB registers, treatment cards and information from health centre registers. Information was collected on number of cases, types of TB and treatment outcomes using standardised definitions. RESULTS: There were 22,982 cases of TB registered in Malawi in 1998, of whom 2,739 (11.9%) were children. Children accounted for 1.3% of all case notifications with smear-positive pulmonary TB (PTB), 21.3% with smear-negative PTB and 15.9% with extra-pulmonary TB (EPTB). Estimated rates of TB in children were 78/ 100,000 in those aged less than one year, 83/100,000 in those aged 1-4 years and 33/100,000 in those aged 5-14 years. A significantly higher proportion of TB cases was diagnosed in central hospitals. Only 45% of children completed treatment. There were high rates of death (17%), default (13%) and unknown treatment outcomes (21%). Treatment outcomes were worse in younger children and in children with smear-negative PTB. Treatment completion was best (76%) and death rates lowest (11%) for the 127 children with smear-positive PTB. CONCLUSION: Childhood TB is common in Malawi and treatment outcomes are poor. Research should be directed towards improved diagnosis and follow-up of children with TB, and the National TB Programme should support appropriate management of childhood contacts of smear positive PTB cases.     

Comparison of extra-pulmonary and pulmonary tuberculosis cases: factors influencing the site of reactivation.

SETTING: Mycobacterium tuberculosis bacilli spread by the hematogenous route during primary infection and reactivate later. OBJECTIVE: To compare factors influencing the reactivation site. DESIGN: A total of 236 pulmonary tuberculosis (PTB) and 139 extra-pulmonary TB (EPTB) cases were compared in terms of age, co-morbid disease, immunosuppressive drug use, history of contact with a PTB case in a close relative, history of tuberculosis, smoking habit and alcohol intake. RESULTS: The sex ratio of EPTB and PTB cases was significantly different (P < 0.001): respectively 74% of EPTB cases and 34% of PTB cases were females; 53.3% of PTB cases and 23% of EPTB cases were smokers (P < 0.001); and the disease appeared within the first 5 years after contact in 23.7% of EPTB cases compared to 72.6% in PTB cases (P < 0.001). In logistic regression analysis, gender (OR = 3.69), smoking habit (OR = 0.54) and interval between contact and disease (OR = 1.07) were found to influence the reactivation site. CONCLUSION: The probability of PTB development was higher in males, in smokers and within the first 5 years of contact. In contrast, the probability of EPTB development was higher in females and after 5 years of contact.     

Extra-pulmonary manifestations in a large metropolitan area with a low incidence of tuberculosis.

BACKGROUND: The increases in extra-pulmonary tuberculosis (EPTB) have been largely due to human immunodeficiency virus co-infection. The rates of EPTB have remained constant despite the decline in pulmonary tuberculosis (PTB) cases. OBJECTIVE: To evaluate covariates associated with EPTB. METHODS: A 4-year cohort of EPTB patients was compared with PTB cases. Enrollees were assessed for TB risk, medical records were reviewed, and Mycobacterium tuberculosis isolates were fingerprinted. RESULTS: We identified 538 EPTB cases (28.6%) in a total of 1878 enrollees. The most common sites of infection were lymph nodes (43%) and pleura (23%). EPTB cases included 320 (59%) males, 382 (71%) patients were culture-positive, and 332 (86.9%) patient isolates were fingerprinted. Fewer EPTB than PTB patients belonged to clustered M. tuberculosis strains (58% vs. 65%; P = 0.02). A multivariate model identified an increased risk for EPTB among African Americans (OR = 1.9, P = 0.01), HIV-seropositive (OR = 3.1, P < 0.01), liver cirrhosis (OR = 2.3, P = 0.02), and age <18 years (OR = 2.0, P = 0.04). Patients with concomitant pulmonary and extra-pulmonary infections were more likely to die within 6 months of TB diagnosis (OR = 2.3, P < 0.01). CONCLUSIONS: African American ethnicity is an independent risk factor for EPTB. Mortality at 6 months is partly due to the dissemination of M. tuberculosis and the severity of the underlying co-morbidity.     

Characteristics of adults and children diagnosed with tuberculosis in Lilongwe,Malawi: findings from an integrated HIV/TB clinic

Objectives To describe initial registration characteristics of adult and paediatric TB patients at a large, public, integrated TB and HIV clinic in Lilongwe, Malawi, between January 2008 and December 2010. Methods Routine data on patient with TB category and TB type, stratified by HIV and ART status, were used to explore differences in proportions among TB only, TB/HIV co‐infected patients not on ART and TB/HIV co‐infected patients on ART using chi‐square tests. Trends over time illustrate strengths and weaknesses of integrated service provision. Results Among 10 143 adults, HIV ascertainment and ART uptake were high and increased over time. The proportion of relapse was highest among those on ART (5%). The proportion of smear‐positive pulmonary TB (PTB) was highest among HIV‐negative patients with TB (34.9%); extra‐pulmonary TB (EPTB) was lowest among TB only (16.2%). Among 338 children <15 years, EPTB and smear‐positive PTB were more common among TB‐only patients. Time trends showed significant increases in the proportion of adults with smear‐positive PTB and the proportion of adults already on ART before starting TB treatment. However, some co‐infected patients still delay ART initiation. Conclusions HIV ascertainment and ART uptake among co‐infected patients are successful and improving over time. However, delays in ART initiation indicate some weakness linking TB/HIV patients into ART during TB follow‐up care. Improved TB diagnostics and screening efforts, especially for paediatric patients, may help improve quality care for co‐infected patients. These results may aid efforts to prioritise TB and HIV prevention, education and treatment campaigns for specific populations.     

Pathways from first health care seeking to diagnosis: obstacles to tuberculosis care in rural China.

OBJECTIVE: To examine health care seeking pathways for patients with tuberculosis (TB) and barriers related to these pathways in counties under the National TB Control Programme in rural China. METHODS: A cross-sectional study was conducted in two counties of east China in 2004-2005. A total of 557 TB patients were recruited and interviewed by physicians at the time of TB diagnosis. RESULTS: Of 557 participants, 13.3% had presented to a specialised county TB dispensary (CTD) directly after onset of symptoms, 31.4% had first sought care at a village health station and 51.2% had visited a township or county hospital first. The proportion of referral by a first health care provider to a CTD was highest in county level hospitals (73.5%) and lowest in village health stations (21.7%). The most prompt pathway from first health care seeking to TB diagnosis was to visit a CTD directly, with a median provider's delay of only one day. There was an increase in provider's delay when more health facilities were involved. CONCLUSION: To improve direct referral from general health care providers, especially village health care workers, to TB specialists would significantly shorten the delays in TB diagnosis in rural China.     

Patient and health care system delays in Queensland tuberculosis patients, 1985-1998.

SETTING: Queensland tuberculosis (TB) control centre QTCC). OBJECTIVE: To investigate patient and health care system delays in the diagnosis of active TB in Queensland. DESIGN: Analysis of data extracted from the QTCC database and review of charts. Symptomatic patients with bacteriologically or histologically proven TB were considered as a total group and a pulmonary smear-positive (PSP) group. RESULTS: The median patient delays were 29 days (total group) and 30 days (PSP group). The median health care system delays were 22 days (total group) and 11 days (PSP group). There were significant trends towards increasing health care system delays with increasing age and longer residency of migrants in Australia. Health care system delays were significantly longer for females and those aged over 45. Migrants from countries of high TB incidence and indigenous Australians had shorter health care system delays compared to non-indigenous Australians. Common reasons for diagnostic delays of more than 90 days were failure to perform appropriate investigations and misdiagnosis of chest X-rays. CONCLUSION: Physicians need to consider including TB in the differential diagnosis in older age groups and migrants with longer residency in Australia. There should be a low threshold for obtaining chest X-rays and sputum samples in patients with persistent cough.     

Factors related to health system delays in the diagnosis of pulmonary tuberculosis in Estonia.

OBJECTIVE: To estimate health system delays (HSD) in the diagnosis of pulmonary tuberculosis (PTB) and its risk factors after major social changes in Estonia, and to assess the ability of a completely reformed health care system to diagnose patients with PTB. METHODS: All newly detected symptomatic culture-positive patients with PTB aged > or = 16 years from Southern Estonia during 2002-2003 (n = 185) were interviewed. HSD was defined as the interval from a patient's first contact with a medical provider to the date of TB diagnosis. RESULTS: The factors significantly associated with HSD greater than the median (19 days) and the 75th percentile (40 days) were smear negativity, absence of cough among symptoms, absence of chest X-ray during the first visit and age > 60 years. A significantly shorter HSD was determined in non-Estonians and unemployed patients. HSD was not associated with the specialty of the doctor first contacted by the patient. CONCLUSION: This study in Southern Estonia shows that the health care system is still managing the diagnosis of PTB without significant delays, even after substantial modifications in the health care system resulting from social reform in a post-socialist country, and that family physicians can manage PTB patients successfully.     

Defining and assessing the maximum number of visits patients should make to a health facility to obtain a diagnosis of pulmonary tuberculosis.

SETTING: All non-private hospitals in Malawi. OBJECTIVES: To determine 1) how many patients with pulmonary tuberculosis (PTB) exceed the maximum number of visits needed for registration as defined by the National Tuberculosis Control Programme, and 2) the factors associated with this delay. DESIGN: Cross-sectional study interviewing hospitalised patients with new smear-positive and smear-negative PTB. RESULTS: Of 380 patients with PTB admitted to the 44 hospitals visited between April and June 2002, 329 (212 smear-positive and 117 smear-negative PTB) were interviewed: 64 (30%) smear-positive PTB patients needed more than five visits, and 44 (37%) smear-negative PTB patients needed more than six visits before being registered and started on treatment. Factors associated with exceeding the maximum number of visits were the first visit being to a health centre, submission of > 1 set of sputum specimens, and > 1 course of antibiotics. The main consequence of exceeding the maximum number of visits was increased duration of cough and increased time spent at health facilities. CONCLUSION: One third of patients exceed the maximum number of visits for registration of PTB. The main consequence of this is an increased duration of cough and an increased time spent at health facilities. Ways to reduce this delay need to be found.     

Clinical diagnosis of smear-negative pulmonary tuberculosis: an audit of diagnostic practice in hospitals in Malawi.

SETTING: Thirty-seven hospitals in Malawi. OBJECTIVE: To audit the hospital practice of clinically diagnosing adults with smear-negative pulmonary tuberculosis (PTB). DESIGN: A cross-sectional survey of adults aged 15 years or above who were registered and receiving inpatient treatment for smear-negative PTB. An assessment of each patient was carried out to determine 1) the number of recommended diagnostic guidelines (cough >3 weeks, no response to antibiotics, negative sputum smears and a chest radiograph compatible with PTB) used by hospital staff in making the diagnosis of PTB, and 2) whether the clinical diagnosis of smear-negative PTB was correct according to criteria set by the study. RESULTS: There were 259 patients, 127 men and 132 women, with a mean age of 37 years; 93% had a cough >3 weeks, 95% had received one or more courses of antibiotics, 92% had submitted sputum samples for smear examination and 97% had chest radiographs performed. In 148 (57%) patients, all four diagnostic guidelines were used, and in 238 (92%) patients three or more were used. The diagnosis of smear-negative PTB was considered correct by study criteria in 203 (78%) patients. In the remainder, 22 (8%) were considered to have extrapulmonary TB and 34 (14%) another diagnosis. CONCLUSION: Hospital practices in the diagnosis of smear-negative PTB are reasonable, although there is room for improvement with in-service training and regular audits of practice.     

Clinical and epidemiological evaluation of tuberculosis in Serbia, 1990-2004.

SETTING: Republic of Serbia, excluding Kosovo. OBJECTIVE: To estimate the clinical and epidemiological pattern of tuberculosis (TB) in Serbia during the period 1990-2004. DESIGN: A retrospective analysis of clinical and epidemiological data on TB patients registered in annual TB reports. RESULTS: During the 15-year period, TB incidence levelled off in Serbia. The slightly decreasing trend occurred in both total pulmonary TB (PTB) and laboratory confirmed PTB (PTB+) incidence (P > 0.05), while the trend of extra-pulmonary TB (EPTB) incidence increased slightly (P > 0.05). During the same period, TB mortality showed a significantly decreasing trend (P < 0.05). The mean annual proportion of PTB+ cases among newly reported PTB cases was 62.7%. The mean proportion of EPTB cases among total TB cases was 6.1%. The mean percentage of cases with resistance to at least one anti-tuberculosis drug was 4.8%. CONCLUSION: Thanks to the good organisation and efficient work of anti-tuberculosis dispensaries in Serbia, as well as to the low incidence of AIDS and low frequency of Mycobacterium tuberculosis resistant strains, TB incidence did not increase during the period observed and TB mortality significantly decreased, despite markedly deteriorated socio-economic conditions during the 1990s.