Preventing recurrent tuberculosis in high HIV-prevalent areas in sub-Saharan Africa: what are the options for tuberculosis control programmes?

Several studies conducted in sub-Saharan Africa have pointed to an increased risk of recurrent TB in patients who are HIV-seropositive. Routine case notification data from the Malawi Tuberculosis Programme, which has improved its registration practices in the last two years, shows that recurrent TB (smear-positive and smear-negative TB) constitutes 9% of total notifications. The objectives of reducing rates of recurrent TB are 1) to complement other interventions to decrease TB incidence rates and transmission of disease, 2) to reduce TB-specific morbidity and mortality and 3) to restore confidence amongst health care staff and patients about the effectiveness of the current TB control strategy. Four possible options for reducing recurrent TB are discussed, and for each option this includes the evidence for effectiveness, current practice and operational considerations. The options are 1) using rifampicin and isoniazid (RH) in the continuation phase of treatment, 2) extending the duration of the continuation phase, 3) providing post-treatment isoniazid prophylaxis to HIV-positive patients who have completed treatment and 4) treating HIV-positive TB patients with highly active antiretroviral therapy (HAART). The last three options all require that TB patients know their HIV serostatus. The authors suggest that this issue of recurrent TB should be considered as one of the important areas for debate and action when considering the dual TB/HIV epidemic.

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.

Decentralisation of treatment for patients with tuberculosis in Malawi: moving from research to policy and practice.

SETTING: Five districts in Malawi. OBJECTIVE: A new oral anti-tuberculosis treatment regimen with different directly observed treatment (DOT) choices in the initial phase of treatment was introduced for new patients in the five districts. The objectives were to determine 1) the site of DOT during the initial phase of treatment, and 2) the effectiveness of the new regimen. DESIGN: Prospective data collection on all tuberculosis (TB) patients registered in a phased approach between 1 July 1997 and 31 December 1998, including site of DOT option in initial phase of treatment, 2-month and 8-month treatment outcomes, 2-month sputum smear conversion in smear-positive pulmonary tuberculosis (PTB) patients and in-patient hospital bed days. RESULTS: There were 6335 new patients: 2671 (42%) with smear-positive PTB, 2211 (35%) with smear-negative PTB and 1453 (23%) with extra-pulmonary TB. The site of the initial phase of treatment was determined in 5790 patients: 1759 (30%) received DOT from guardians, 1465 (25%) from a health centre, 753 (13%) as out-patients from the hospital TB ward and 1813 (32%) remained in hospital. Eight-month treatment completion was 67% for smear-positive PTB patients, 51% for smear-negative PTB patients and 56% for extra-pulmonary TB patients. Two-month outcomes and 8-month treatment outcomes for all out-patient sites of supervision were satisfactory, except that a higher proportion of smear-positive PTB patients under guardian DOT failed to smear convert at 2 months. Over two-thirds of patients received ambulatory treatment out of hospital during the initial phase. CONCLUSION: The new treatment strategy, tested in five districts, was associated with a reduction in hospital bed days and satisfactory treatment outcomes. The results of these studies were vital in helping the National TB Control Programme make an informed decision about phased expansion of the strategy countrywide.

District sputum smear microscopy services in Malawi.

SETTING: Government hospitals and health centres in 23 districts in Malawi. OBJECTIVE: To determine 1) the number and smear-positivity rate of sputum samples submitted at health centres and hospitals, and 2) the time for sputum samples to get from health centres to smear examination. DESIGN: Prospective data collection on sputum specimens coming from health centres to hospital laboratories, and over the equivalent time period, retrospective data collection from laboratory sputum registers. RESULTS: Information was collected over a period of 5.6 months during 1997. Of 21 527 patients submitting sputum samples, 16995 (79%) were from within the hospital and 4532 (21%) were from health centres. Of 15 833 new TB suspects, 12 804 (81%) submitted sputum within the hospital and 3029 (19%) were from health centres. The overall smear-positivity rate was 11.9%: the proportion of new suspects who were smear-positive was significantly higher in health centres (14.1%) compared with hospital-based patients (11.4%, P < 0.05); 27% of all sputum specimens from health centres took 8 days or longer to get to smear examination. Sputum smears were positive from 1-30 days between submission and laboratory examination. CONCLUSION: Fewer sputum samples are submitted at health centres compared with hospitals, and there may be long delays between sputum submission and smear examination. The precise reasons are unclear, but health centre staff need training about the importance of timely case finding procedures.

Is oral intermittent initial phase anti-tuberculosis treatment associated with higher mortality in high HIV-prevalent areas in sub-Saharan Africa?

The Malawi Tuberculosis Programme has evaluated an oral ambulatory treatment regimen (2R3H3Z3E3/6HE) in five districts, and observed a mortality rate of 23% in 2671 new patients with smear-positive pulmonary tuberculosis (PTB). Three studies were performed comparing treatment outcomes between patients treated with 2R3H3Z3E3/6HE and 2SRHZ/6HE using historical data in the same districts and concurrent data in different districts. Using historical comparisons, mortality was significantly higher with 2R3H3Z3E3/6HE than 2SRHZ/6HE. Using concurrent comparisons, mortality was similar, although there was a higher death rate in the first month with the intermittent regimen. The intermittent regimen may be inferior to the established regimen.

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.

Safety in laboratories carrying out sputum smear microscopy: a dilemma for resource-poor countries.

Laboratory conditions and procedures for sputum smear microscopy (acid-fast bacilli) were assessed in 38 hospitals throughout Malawi. Of these, 17 (45%) had an area of less than 25 m2, eight (21%) had a separate room for tuberculosis work, and five (13%) had a safety cabinet. All laboratory personnel wore gloves, but in several hospitals there was no white coat, face mask, protective apron or soap for washing hands. Different disinfectants were used to clean work surfaces, only one laboratory decontaminated sputum specimens before disposal, and the laboratory cleaner was usually responsible for waste disposal. Laboratory conditions and safety procedures in Malawi are poor, indicating a need for education, training and supervision of staff.

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.

Viability of stored sputum specimens for smear microscopy and culture.

A laboratory study was performed to determine how long sputum specimens from smear-positive tuberculosis patients can be stored at room temperature or in the refrigerator and retain a positive acid-fast bacilli (AFB) smear or a positive mycobacterial culture. Sputum samples from 30 patients were examined up to 4 weeks and samples from 13 patients examined up to 8 weeks. Provided samples had not dried out, all sputum smears remained AFB positive up to 4 and 8 weeks. In both patient groups, at 4 weeks 37-39% of specimens at room temperature grew mycobacteria compared with 54-67% of specimens stored in the refrigerator. These results have implications for tuberculosis programme policy.

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.

Characteristics, management and outcome of patients with recurrent tuberculosis under routine programme conditions in Malawi.

SETTING: All 43 non-private hospitals in Malawi, which registered TB cases between 1 July 1999 and 30 June 2000. OBJECTIVES: To determine 1) the characteristics, management and treatment outcome, 2) timing of the previous episode of TB, and 3) pattern of drug resistance in patients registered with recurrent smear-positive pulmonary TB. DESIGN: Retrospective data collection using TB registers and laboratory culture and drug sensitivity registers. RESULTS: There were 748 recurrent patients; data were available for 747. Of these, 487 (65%) successfully completed a re-treatment regimen, 185 (25%) died and the remainder had another outcome. Information about previous TB was recorded for 491 (66%) patients. In 286 (58%) there were 2 years or less between completing and re-starting treatment. Only 307 (41%) patients had sputum sent for culture and drug sensitivity tests. In 164 patients with cultures of Mycobacterium tuberculosis, 122 (81%) were fully sensitive, 25 (15%) had resistance to isoniazid and/or streptomycin, and 6 (4%) had resistance to isoniazid and rifampicin (MDR-TB). CONCLUSION: Patients with recurrent TB had acceptable treatment outcomes, and most had fully sensitive organisms. Over half had recurrent TB 2 years or less after completing treatment. Ways to prevent recurrence need to be investigated and implemented in the field.

Decentralisation of tuberculosis services in an urban setting, Lilongwe, Malawi.

SETTING: Lilongwe, the capital of Malawi, one of the countries in the world badly affected by the human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS) epidemic. OBJECTIVE: In the face of a rising burden of tuberculosis (TB) fuelled by HIV, to evaluate the impact on the Lilongwe district tuberculosis programme performance of decentralisation of TB services, including extending the range of options for supervision of directly observed treatment (DOT) during the initial phase of treatment, and using a fully oral, intermittent regimen. DESIGN: Prospective assessment under programme conditions of 1) duration of hospital stay, 2) bed occupancy and 3) 8-month treatment outcomes in a cohort of patients registered before (1997) and after (1998) the introduction of decentralisation of TB services. RESULTS: The number of new patients (all forms) registered in Lilongwe district was 3144 in 1997 and 3761 in 1998. There were significant differences (P < 0.05) between all outcomes that were compared. In 1998, bed occupancy dropped by 38%; among smear-positive patients, the average length of hospital stay fell from 58 days in 1997 to 16, the cure rate was higher (64% vs. 56%), default rate was lower (5% vs. 19%), and treatment completion rate was lower (2% vs. 4%); among smear-negative patients, the treatment completion rate was higher (50% vs. 33%), default rate was lower (23% vs. 55%), and death rate was higher (17% vs. 4%). This death rate is attributable to improved follow-up and reporting of outcomes, rather than to increased deaths. CONCLUSION: Programme implementation of decentralised TB services in Lilongwe, including an extended range of supervision options for DOT and the use of an ambulatory treatment regimen, achieved reduced hospital stay and bed occupancy and good treatment outcomes.

Using a bus service for transporting sputum specimens to the Central Reference Laboratory: effect on the routine TB culture service in Malawi.

SETTING: All non-private hospitals in Malawi that registered TB cases in 2001, during which there was a bus service for transporting sputum specimens to the Central Reference Laboratory (CRL) for mycobacterial culture and drug sensitivity testing (CDST). OBJECTIVES: To determine the performance of the system of collecting and processing sputum specimens from patients with recurrent smear-positive pulmonary TB through to CDST. DESIGN: Structured interviews with TB Officers, and retrospective data collection using TB and laboratory registers. RESULTS: There were 964 patients with recurrent smear-positive PTB. TB Officers took responsibility for collecting and transporting sputum to the CRL, and 73% reported using the bus service. Sputum specimens from 384 (40%) patients arrived at the CRL. Of these, 40% were found to have negative concentrated smears at the CRL, and 36% of specimen sets arriving at CRL were successfully cultured for DST. Most specimens had been collected after the start of anti-tuberculosis treatment. Although delays in collection adversely affected culture, only 43% of specimen sets collected on or before the first day of treatment yielded Mycobacterium tuberculosis. CONCLUSION: Problems were identified at all stages of the system and strategies to remedy these are being put in place.

Tuberculosis control in Malawian prisons: from research to policy and practice.

Following an operational research study in Zomba Central Prison, Malawi, in 1996, the National Tuberculosis Control Programme (NTP) and the Prison Medical Services worked together to improve the diagnosis and treatment of tuberculosis (TB) in prisoners. Prisoners are screened for TB on admission and during their prison sentences. A system was established of treating patients, according to NTP guidelines, while in prison and on discharge from prison. Monitoring and evaluation is undertaken using TB officers at district and regional level, and 6-monthly meetings are held with all stakeholders and the central unit to collate data and review prison TB control activities.

Auditing the new decentralised oral treatment regimens in Malawi.

SETTING: All 44 non-private hospitals in Malawi treating tuberculosis (TB) cases in which oral regimens were used allowing patients during the initial phase to receive directly observed treatment (DOT) from health centres or guardians at home. OBJECTIVES: A country-wide audit of the oral regimens to determine: 1) TB ward bed occupancy rates, 2) patient DOT options, 3) patients' knowledge of treatment and 4) treatment outcomes compared to those obtained with previous treatment regimens. DESIGN: Retrospective data collection using registers and treatment cards. Prospective interviews with patients. Inspections of TB wards. RESULTS: There were 1513 TB beds occupied by 807 (53%) TB patients. Over 50% of 4793 patients registered with different types of TB chose guardian-based DOT. For 266 patients with pulmonary TB the correct knowledge about total duration of treatment (45%), all three DOT options (62%) and the months for giving follow-up sputum (16%), was poor. There were differences in treatment outcomes between TB patients on oral compared with previous regimens. With oral regimens, rates of unknown outcome were high. CONCLUSION: Oral treatment regimens are associated with reduced bed occupancy rates on TB wards. However, rates of unknown outcome are increased, and TB control is therefore weakened.

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.

Care seeking behaviour and diagnostic processes in patients with smear-positive pulmonary tuberculosis in Malawi.

SETTING: Government hospitals in five districts in Malawi. OBJECTIVE: To determine care seeking behaviour and diagnostic processes in patients newly diagnosed with smear-positive pulmonary tuberculosis (PTB). DESIGN: Structured questionnaires completed by interview between January to September 1998. RESULTS: During the study period 1,518 patients were registered with PTB, of whom 1,099 (72%) were interviewed. The median delay between onset of cough and diagnosis was 8 weeks. There was a variable pattern of care seeking behaviour, with 70% of patients initially visiting a place of orthodox medical care and 30% visiting traditional healers, grocery shops, etc. Of these, 867 (79%) patients had one or more subsequent contacts for help, with these visits targeted more to orthodox medical care. At all stages, antibiotics resulted in symptomatic improvement in up to 40% of cases. There was a median time of 7 weeks between cough and first submission of sputum specimens. Almost all patients received sputum smear results after a median length of 4 days; 474 (43%) of patients were only aware of their diagnosis at the time of receiving smear results, this observation being significantly associated with lack of schooling and not knowing another person with TB. CONCLUSION: More needs to be done to educate communities and non-orthodox care providers about the diagnosis and treatment of TB.

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.

Tuberculosis in health care workers in Malawi.

Although sub-Saharan Africa has the highest rates of tuberculosis (TB) and human immunodeficiency virus (HIV) infection in the world, the rates of TB amongst its health care workers (HCWs) are poorly documented. We therefore conducted a country-wide investigation. All district/government and mission hospitals in Malawi that diagnose and care for TB patients were visited in order to obtain information on hospital-based HCWs and their incidence of TB in 1996. Hospital TB case loads, country-wide TB notification numbers and national population estimates for 1996 were obtained, which enabled TB case notification rates to be calculated. In 1996, 108 (3.6%) of 3042 HCWs from 40 hospitals were registered and treated for TB: 22 with smear-positive pulmonary TB (PTB), 40 with smear-negative PTB and 46 with extrapulmonary TB. The overall case fatality rate was 24%. Compared with the adult general population aged > or = 15 years, the relative risk [95% confidence interval (CI)] in HCWs of all types of TB was 11.9 [9.8-14.4], of smear-positive PTB 5.9 [3.9-9.0], of smear-negative PTB 13.0 [9.5-17.7] and of extrapulmonary TB 18.4 [13.8-24.6], P < 0.05. The 1996 hospital TB case load ranged from 29 to 915: there were no cases of TB in HCWs in hospitals whose case load was < or = 100 patients, while the TB case rate among HCWs was similar in hospitals with annual case loads of 101-300 or > 300. The annual risk of TB was high among all categories of HCW, especially clinical officers. This study shows a high rate of TB in HCWs in Malawi, and emphasizes the need for practical and affordable control measures for the protection of HCWs from TB in low-income countries.

Treatment outcome of patients with smear-negative and smear-positive pulmonary tuberculosis in the National Tuberculosis Control Programme, Malawi.

National tuberculosis control programmes (NTPs) in sub-Saharan Africa do not routinely record or report treatment outcome data on smear-negative pulmonary tuberculosis (PTB) patients. Twelve-month treatment outcome on patients with smear-negative PTB registered in all district and mission hospitals in Malawi during the year 1995 was collected, and was compared with 8-month treatment outcome in smear-positive PTB patients registered during the same period. Of 4240 patients with smear-negative PTB, 35% completed treatment, 25% died, 9% defaulted and 7% were transferred to another district with no treatment outcome results available. In 24% of patients treatment cards were lost and treatment outcome was unknown. These results were significantly inferior to those obtained in 4003 patients with smear-positive PTB in whom 72% completed treatment, 20% died, 4% defaulted, 2% were transferred and 1% had positive smears at the end of treatment. These differences between patients with smear-negative and smear-positive PTB were similar when analysed by sex and by most age-groups. Higher mortality rates in patients with smear-negative PTB are probably attributable to advanced HIV-related immunosuppression, and higher default and treatment unknown rates probably reflect the lack of attention paid by TB programme staff to this group of patients. As a result of this country-wide study the Malawi NTP has started to record routinely the treatment outcomes of smear-negative TB patients and has set treatment completion targets of 50% or higher for this group of patients.