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.     

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.     

The diagnosis of smear-negative pulmonary tuberculosis: the practice of sputum smear examination in Malawi.

SETTING: Forty hospitals in Malawi (3 central, 22 district and 15 mission) performing smear microscopy and registering tuberculosis patients. OBJECTIVE: To determine, in patients aged 15 years or above, 1) the proportion with smear-negative pulmonary tuberculosis (PTB) who had sputum smears examined, 2) the number of sputum smears examined per patient, and 3) the proportion of patients registered with smear-positive and smear-negative PTB. DESIGN: Data collection during three 6-month periods, from January 1997 to June 1998, using tuberculosis registers, laboratory sputum registers and quarterly reports. RESULTS: Of 6301 smear-negative PTB patients, 84% had sputum smears examined, the rate increasing from 76% in January-June 1997, to 85% in July-December 1997, to 89% in January-June 1998. Of patients who submitted sputum (where the number of smears was recorded), 99% had two or more smears examined and 93% had three smears examined. In district and mission hospitals performance improved over time, while in central hospitals results were more variable. During the same 18-month period 21 422 patients aged 15 years or more were registered with PTB: 59% with smear-positive PTB and 41% with smear-negative PTB; this pattern was similar in each 6-month period. CONCLUSION: The study suggests that it is reasonable to aim for a target of 90% or more of smear-negative PTB patients having sputum smears examined.     

Undiagnosed tuberculosis in a community with high HIV prevalence: implications for tuberculosis control

BACKGROUND: Although failure of tuberculosis (TB) control in sub-Saharan Africa is attributed to the HIV epidemic, it is unclear why the directly observed therapy short-course (DOTS) strategy is insufficient in this setting. We conducted a cross-sectional survey of pulmonary TB (PTB) and HIV infection in a community of 13,000 with high HIV prevalence and high TB notification rate and a well-functioning DOTS TB control program. METHODS: Active case finding for PTB was performed in 762 adults using sputum microscopy and Mycobacterium tuberculosis culture, testing for HIV, and a symptom and risk factor questionnaire. Survey findings were correlated with notification data extracted from the TB treatment register. RESULTS: Of those surveyed, 174 (23%) tested HIV positive, 11 (7 HIV positive) were receiving TB therapy, 6 (5 HIV positive) had previously undiagnosed smear-positive PTB, and 6 (4 HIV positive) had smear-negative/culture-positive PTB. Symptoms were not a useful screen for PTB. Among HIV-positive and -negative individuals, prevalence of notified smear-positive PTB was 1,563/100,000 and 352/100,000, undiagnosed smear-positive PTB prevalence was 2,837/100,000 and 175/100,000, and case-finding proportions were 37 and 67%, respectively. Estimated duration of infectiousness was similar for HIV-positive and HIV-negative individuals. However, 87% of total person-years of undiagnosed smear-positive TB in the community were among HIV-infected individuals. CONCLUSIONS: PTB was identified in 9% of HIV-infected individuals, with 5% being previously undiagnosed. Lack of symptoms suggestive of PTB may contribute to low case-finding rates. DOTS strategy based on passive case finding should be supplemented by active case finding targeting HIV-infected individuals.     

Mortality rates and recurrent rates of tuberculosis in patients with smear-negative pulmonary tuberculosis and tuberculous pleural effusion who have completed treatment.

SETTING: Queen Elizabeth Central Hospital, Blantyre, and Zomba Central Hospital, Zomba, Malawi. OBJECTIVE: To follow-up human immunodeficiency virus (HIV) seropositive and HIV-seronegative patients with smear-negative pulmonary tuberculosis (PTB) and pleural TB who had completed treatment with two different regimens in Blantyre and Zomba, and to assess rates of mortality and recurrent TB. DESIGN: Patients with smear-negative and pleural TB who had completed 8 months ambulatory treatment in Blantyre or 12 months standard treatment in Zomba and who were smear and culture negative for acid-fast bacilli at the completion of treatment were actively followed every 4 months for a total of 20 months. RESULTS: Of 248 patients, 150 with smear-negative PTB and 98 with pleural TB, who completed treatment and were enrolled, 205 (83%) were HIV-positive. At 20 months, 145 (58%) patients were alive, 85 (34%) had died and 18 (7%) had transferred out of the district. The mortality rate was 25.7 per 100 person-years, with increased rates strongly associated with HIV infection and age >45 years. Forty-nine patients developed recurrent TB. The recurrence rate of TB was 16.1 per 100 person-years, with increased rates strongly associated with HIV infection, having smear-negative PTB and having received 'standard treatment'. CONCLUSION: High rates of mortality and recurrent TB were found in patients with smear-negative PTB and pleural effusion during 20 months of follow-up. TB programmes in sub-Saharan Africa must consider appropriate interventions, such as co-trimoxazole and secondary isoniazid prophylaxis, to reduce these adverse outcomes.     

Poor attendance at a child TB contact clinic in Malawi.

SETTING: Child tuberculosis (TB) contact clinic, Queen Elizabeth Central Hospital, Blantyre, Malawi. DESIGN: Patients registered with smear-positive pulmonary TB (PTB) were encouraged to bring childhood household contacts to the clinic for assessment and management. Data of TB cases registered over the same period were collected from the Blantyre District TB Office. RESULTS: Attendance at the contact clinic was very poor, representing only 7.7% of all adults registered with smear-positive PTB over 17 months, and was significantly lower for potential male source cases than females (OR 0.36, 95% CI 0.23-0.55, P < 0.001). DISCUSSION: Improved uptake and implementation of child contact management in Malawi is a challenge.     

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.     

Outcome of patients with tuberculosis who transfer between reporting units in Malawi.

SETTING: All 43 non-private hospitals in Malawi which in 1999 registered and treated patients with tuberculosis (TB). OBJECTIVE: To determine the proportion of TB patients who transferred from one reporting unit to another and their treatment outcome, and to compare outcome results between the main TB register and the transfer-in register. DESIGN: Retrospective data collection, using the main TB register and transfer-in register, on all patients registered in Malawi in 1999. RESULTS: There were 24,908 patients, of whom 3249 (13%) in total were transfers. Significantly more patients transferred from mission hospitals (23%) compared with central (8%) or district (5%) hospitals (P < 0.001). The date of transfer was recorded for 1406 patients, of whom 1170 (83%) transferred in the first 10 weeks. Respectively 45% and 58% of transfer patients had unknown outcomes in the main TB register and transfer-in register; these rates were significantly lower in smear-positive pulmonary TB (PTB) patients. A total of 1357 patients were entered into transfer-in registers; 694 patients had matched names and/or registration numbers in both registers. Of the matched patients, 373 (54%) had similar treatment outcomes. CONCLUSION: It is common for patients to transfer between treatment units, but the quality of the data for patients who transfer is poor, and needs to be improved.     

全国初治涂阴肺结核病例登记现状分析

目的分析全国各省初治涂阴肺结核病例登记现状,为评价初治涂阴肺结核病例诊断质量提供依据。方法根据2004—2005年全国结核病防治规划报表中初治涂阴和初治涂阳肺结核病例登记资料,分析各省2年初治涂阴肺结核病例登记率变化和增长幅度;统计各省及不同地区初治涂阴与初治涂阳肺结核病例登记率;对各省初治涂阴与初治涂阳肺结核病例登记率进行直线回归分析。结果2005年全国登记初治涂阴肺结核病例316 405例,登记率为24.27/10万,各省登记率在6.01/10万72.17/10万;2005年登记初治涂阴病例数比2004年增加了19.9%,其中2个省登记数呈负增长,其余各省登记数增长了0.5%62.3%;2005年全国初治涂阳病例登记率是涂阴病例登记率的1.5倍,其中23个省初治涂阳病例登记率高于涂阴病例登记率,8个省相反;初治涂阴病例占初治涂阳病人登记率的比例,京津沪地区为149.28%,非项目地区为83.6%,项目地区为50.3%;对涂阳和涂阴病例登记率进行直线回归分析,回归方程y=22.342+0.563 6x。结论对初治涂阴肺结核患者实行免费政策后,全国涂阴肺结核病例登记率提高。但各省初治涂阴病例登记率和增长幅度以及涂阴病例登记率与涂阳病例登记率的比例悬殊。由于涂阴病例诊断困难,对于涂阴病例登记率高或增长幅度大的地区,特别在DOTS执行时间短和人力资源有限的地区,应对涂阴病例诊断质量予以进一步检查和评价。     

A unified treatment regimen for new cases of tuberculosis in resource-poor countries: a study in a rural district in Malawi.

An oral ambulatory unified treatment regimen was introduced in Ntcheu District, Malawi, between April 1996 and June 1997 for all new patients (600) with tuberculosis (TB). There was no change in the case finding pattern compared with the previous 5 years; 65% of new smear-positive pulmonary tuberculosis (PTB) patients completed treatment, not significantly different compared with the previous 3 years. Treatment completion was significantly lower in patients with smear-negative PTB and extra-pulmonary tuberculosis, due mainly to high mortality rates (40% and 41% respectively). In a rural district with high human immunodeficiency virus sero-prevalence rates in TB patients, case finding and end of treatment outcome of the oral unified regimen were comparable to those of previous regimens.     

The first-three year report of the Tuberculosis Control Project, Lumbini, Rupandehi

The Tuberculosis Control Project, Lumbini, Rupandehi (TCPLR) is a bilateral cooperative venture between two NGO's, the Nepal Anti-Tuberculosis Association (NATA) and the Japan Anti-Tuberculosis Association (JATA), which consists of planning and implementing pilot tuberculosis control activities in Lumbini, Rupandehi district in Nepal, aiming at achieving high cure rate of newly detected smear-positive pulmonary tuberculosis patients before introducing DOTS strategies. Between December 1993 and July 1996, 349 tuberculosis (TB) cases were enrolled in the TCPLR. The categories of cases were as follows: 138 cases (40%) of new smear-positive pulmonary TB [new Sm(+) PTB], and 54 cases (15%) of smear positive pulmonary TB other than new Sm(+) PTB [other Sm(+) PTB] including such cases as continued treatment and relapse, 106 cases (30%) of new smear-negative TB [new Sm(-) TB], and 51 cases (15%) of other smear-negative TB other than New Sm(-) PTB [other Sm(-) TB]. The number and proportion of new Sm(+) PTB cases enrolled in the project have been increasing [6 cases (23%) for the first year, 102 cases (54%) for the third year] although the proportion is still low (40% overall). The regimens of chemotherapy in the initial intensive and the continuation phases of treatment according to the categories of TB were as follows: New Sm(+) PTB; 2HRZE(S)/6HE, other Sm(+) PTB; 2HRZES/1HRZE/5HRE, and Sm(-) TB; 2HRZ/6HE. The proportion of cases treated by the appropriate regimen of chemotherapy has increased. The cohort analysis of the treatment outcome of the cases enrolled in the project showed the following. The proportion of cured cases plus smear-unconfirmed cases completing treatment among new Sm(+) PTB was 74% overall, however, the proportion of defaulters increased in the third year. The proportion of cured cases plus smear-unconfirmed cases completing treatment among other Sm(+) PTB cases was 66% overall, which is slightly lower than that of new Sm(+) PTB cases, however, the difference was not so marked. The proportion of treatment completed cases among smear-negative pulmonary TB cases was 77% overall, however, proportion of defaulters increased in the third year. The treatment outcome in this report was obtained before the adoption of DOTS strategies: However, it showed that cure and treatment completion rates were comparable to those obtained in the SEARO countries which adopt DOTS strategies. The treatment outcome could be improved after the introduction of DOTS strategies in 1997.     

Tuberculosis in health care workers in a central hospital in Malawi.

A retrospective study was carried out at Lilongwe Central Hospital, Malawi, to determine 1) the tuberculosis case notification rate in health care workers (HCW) in 2001, and 2) whether NTP guidelines were adhered to in diagnosing TB. Of 571 HCWs, 33 (6%) were notified with TB in 2001, giving a TB case notification rate of 5780/100,000. Patient attendants had higher rates of TB than nurses, ward attendants and doctors, but otherwise there were no significant differences between the HCW categories. NTP diagnostic guidelines were not properly followed, particularly in diagnosing smear-negative TB; in HCWs with smear-negative PTB, 64% had no sputum smears examined. The rate of TB in HCWs in a central hospital in Malawi was high, although lack of adherence to guidelines might have resulted in overdiagnosis.     

What causes smear-negative pulmonary tuberculosis in Malawi, an area of high HIV seroprevalence?

SETTING: The Central Hospital and the District Tuberculosis (TB) Registry in Lilongwe, the capital of Malawi. In this setting smear-negative pulmonary tuberculosis (PTB) is diagnosed using clinical and radiographic criteria for TB, and mycobacterial cultures are not routinely available. OBJECTIVE: To determine the proportion of patients being registered for smear-negative PTB treatment in Lilongwe who have TB that can be confirmed microbiologically. DESIGN: Prospective cohort study of patients about to start treatment under operational conditions for smear-negative PTB in Lilongwe between October 1997 and June 1998. Patients referred to the study team underwent a detailed clinical re-assessment, testing for human immunodeficiency virus (HIV), repeat sputum smear microscopy for acid-fast bacilli and mycobacterial cultures of sputum and blood. Bronchoscopy and bronchoalveolar lavage (BAL) were performed and BAL fluid was examined for TB, Pneumocystis carinii and other fungi. RESULTS: Of 352 smear-negative PTB suspects assessed, the diagnosis of TB was confirmed in 137 (39%) cases. Eighty-nine per cent of patients assessed were HIV-positive, of whom 81% met the expanded case definition for the acquired immune-deficiency syndrome (AIDS). CONCLUSION: TB was the most commonly confirmed diagnosis amongst patients about to start treatment for smear-negative PTB in an area of high background HIV seroprevalence.     

Management and outcome of tuberculosis patients who fail treatment under routine programme conditions in Malawi.

SETTING: All 43 non-private hospitals (three central, 22 district and 18 mission) in Malawi that registered and treated TB cases between 1 July 1999 and 30 June 2000. OBJECTIVES: To determine 1) the number of new smear-positive PTB patients who failed treatment, 2) the management of patients who failed, 3) their treatment outcome and 4) culture and drug sensitivity results. DESIGN: Retrospective data collection using TB registers and laboratory culture and drug sensitivity registers. RESULTS: Ninety patients failed treatment, 60 (67%) at 5 months and 30 (33%) at the end of treatment. Sixty-four (71%) failure patients were registered and commenced on anti-tuberculosis treatment. Of these, 95% were registered in the same hospital as before, 89% were given a different TB registration number, 67% were correctly registered as 'failures' and 61% were treated within one month of failing the previous regimen. Forty-eight (75%) re-treated patients were cured. Only 31 (34%) of the 90 patients had sputum sent for culture and drug sensitivity testing. In 11 patients with cultures of M. tuberculosis, eight were fully sensitive and three had mono-resistance to isoniazid. CONCLUSION: While the outcome of failure patients who start retreatment is good, there are several programmatic deficiencies that need to be corrected.     

Gender differences in relation to sputum submission and smear-positive pulmonary tuberculosis in Malawi.

OBJECTIVE: To examine gender differences in sputum submission and sputum smear positivity. METHODS: Laboratory registers in all diagnostic units in eight districts in Malawi were examined for the years 1995 and 1996. RESULTS: During a 12-month period (averaged between 1995 and 1996), 26,624 new TB suspects submitted sputum samples, 3282 of which (12.3%) were smear-positive. Significantly more males submitted sputum (52%) compared with females (48%), and significantly more males (53%) were smear-positive compared with females (47%, P < 0.05). Rates of sputum submission per 100,000 adults were also significantly higher for males (1203) than females (1032). CONCLUSION: In Malawi, fewer females are submitting sputum samples and are being diagnosed with smear-positive TB compared with males.     

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.     

Long-term outcome in patients registered with tuberculosis in Zomba, Malawi: mortality at 7 years according to initial HIV status and type of TB.

SETTING: Zomba Central Hospital, Malawi. OBJECTIVES: To determine the outcome of all adult patients who were registered for tuberculosis (TB) treatment 7 years previously according to initial human immunodeficiency virus (HIV) status and type of TB. DESIGN: A retrospective cohort study of adult patients registered for TB treatment between July and December 1995. Follow-up at patients' homes was performed at the end of treatment, at 32 months and at 84 months (7 years) from the time of TB registration. FINDINGS: Eight hundred and twenty-seven TB patients were registered: 793 had concordant HIV test results, of whom 612 (77%) were HIV-positive. At 7 years, 136 (17%) patients were alive, 539 (65%) had died and 152 (18%) were lost to follow-up. The death rate for all TB patients was 23.7 per 100 person-years of observation. HIV-positive patients had higher death rates than HIV-negative patients (hazard ratio [HR] 2.2, 95% confidence interval [95%CI] 1.7-2.8). Death rates in smear-negative pulmonary TB patients (HR 2.1, 95%CI 1.7-2.6) and in patients with extra-pulmonary TB (HR 1.7, 95% CI 1.3-2.0) were higher than in patients with smear-positive PTB. CONCLUSIONS: There was a high mortality rate in TB patients during and after anti-tuberculosis treatment. Adjunctive treatments to reduce death rates are urgently needed.     

Pulmonary tuberculosis in young Korean soldiers: incidence, drug resistance and treatment outcomes.

OBJECTIVE: To determine the incidence and treatment outcomes of pulmonary tuberculosis (PTB) in young soldiers of South Korea. DESIGN: From 2000 to 2004, all soldiers with a new diagnosis of tuberculosis (TB) were enrolled in the study, based on the official records of the Armed Forces Medical Command. The demographic and clinical data of the cases were evaluated retrospectively. RESULTS: A total of 3115 TB cases were reported during the study period, of whom 2071 (66.5%) were reported as PTB. The annual incidence rates of PTB were 96.4 per 100,000 population in 2000, 89.3 in 2001, 67.6 in 2002, 60.2 in 2003, and 63.1 in 2004. A total of 270 patients diagnosed and treated at the Armed Forces Capital Hospital were analysed. Of the Mycobacterium tuberculosis isolates, 87.4% were susceptible to all available anti-tuberculosis drugs; 253 (93.7%) patients eventually completed initial anti-tuberculosis treatment. Among the patients with smear-positive PTB, the cure rate was 89.3% (100/112). CONCLUSION: Our results demonstrate that the incidence of PTB in Korean soldiers, although still high, was declining steadily. With good case management, the overall success rate of initial treatment was approximately 90%.     

Efficacy of an unsupervised ambulatory treatment regimen for smear-negative pulmonary tuberculosis and tuberculous pleural effusion in Malawi.

SETTING: Queen Elizabeth Central Hospital, Blantyre, and Zomba Central Hospital, Zomba, Malawi. OBJECTIVE: To evaluate treatment outcome of unsupervised ambulatory treatment (2R3H3Z3/2TH[EH]/4H) in Blantyre and 'standard' treatment (1STH[SEH]/11TH[EH]) in Zomba in human immunodeficiency virus (HIV) seropositive and seronegative patients with smear-negative pulmonary tuberculosis (PTB) and pleural TB. DESIGN: All patients with smear-negative and pleural TB registered between 1 April and 31 December 1995 were assessed for enrolment in the study. Study patients were followed up and 12-month treatment outcomes were recorded. RESULTS: A total of 434 patients, 296 with smear-negative PTB and 138 with pleural TB, were enrolled: 366 (84%) of patients were HIV-positive; 220 (51%) completed treatment, and 144 (33%) died by 12 months. In patients from Blantyre and Zomba, baseline characteristics were similar, apart from older age in those from Zomba, and the proportion of patients who completed treatment and who died were similar. In both sites, significantly higher case fatality rates were found in older patients, HIV-positive patients and patients with pulmonary parenchymal lung disease. CONCLUSION: Unsupervised ambulatory treatment evaluated in this study had an efficacy similar to that of 'standard' treatment. For operational reasons, however, it will not be recommended for widespread use in Malawi's National Tuberculosis Control Programme.