A qualitative evaluation of hospital versus community-based management of patients on injectable treatments for tuberculosis.

BACKGROUND: Patients being treated for recurrent or multidrug-resistant tuberculosis (TB) require long courses of injectable anti-tuberculous agents. In order to maintain strong TB control programmes, it is vital that the experiences of people who receive long-term injectables for TB are well understood. To investigate the feasibility of a novel model of care delivery, a clinical trial (The TB-RROC Study) was conducted at two central hospitals in Malawi. Hospital-based care was compared to a community-based approach for patients on TB retreatment in which 'guardians' (patient-nominated lay people) were trained to deliver injections to patients at home. This study is the qualitative evaluation of the TB-RROC trial. It examines the experiences of people receiving injectables as part of TB treatment delivered in hospital and community-based settings. METHODS: A qualitative evaluation of the TB-RROC intervention was conducted using phenomenographic methods. Trial participants were purposively sampled, and in-depth interviews were conducted with patients and guardians in both arms of the trial. Key informant interviews and observations in the wards and community were performed. Thematic content analysis was used to derive analytical themes. RESULTS: Fourteen patients, 12 guardians and 9 key informants were interviewed. Three key themes relating to TB retreatment emerged: medical experiences (including symptoms, treatment, and HIV); the effects of the physical environment (conditions on the ward, disruption to daily routines and livelihoods); and trust (in other people, the community and in the health system). Experiences were affected by the nature of a person's prior role in their community and resulted in a range of emotional responses. Patients and guardians in the community benefited from better environment, social interactions and financial stability. Concerns were expressed about the potential for patients' health or relationships to be adversely affected in the community. These potential concerns were rarely realised. CONCLUSIONS: Guardian administered intramuscular injections were safe and well received. Community-based care offered many advantages over hospital-based care for patients receiving long-term injectable treatment for TB and their families.

The 'Practical Approach to Lung Health' in sub-Saharan Africa: a systematic review.

SETTING: There is a high burden of respiratory disease in sub-Saharan Africa. To address this problem, the World Health Organization launched the 'Practical approach to Lung Health' (PAL), i.e., locally applicable integrated syndromic algorithms, to improve primary care management of these diseases. OBJECTIVE: To examine the evidence for the impact of PAL on the diagnosis and management of tuberculosis (TB) and other common respiratory problems in sub-Saharan Africa. DESIGN: A systematic review of MEDLINE (1998-2015), EMBASE (1998-2015) and CINAHL (1998-2015) was conducted to find trials evaluating PAL implementation in sub-Saharan Africa. RESULTS: Five studies were found, evaluating three PAL variations: PAL in South Africa (PALSA), PALSA with integrated human immunodeficiency virus treatment (PALSA PLUS) and PAL in Malawi using lay health workers (PALM/LHW). PALSA increased TB diagnosis (OR 1.72, 95%CI 1.04-2.85), as did PALSA PLUS (OR 1.25, 95%CI 1.01-1.55). Cure or completion rates in retreatment cases in PALSA and PALSA PLUS were significantly improved (OR 1.78, 95%CI 1.13-2.76). PALM/LHW, which examined TB treatment success, found no significant improvement (P = 0.578). CONCLUSION: The limited research performed shows that PAL can be effective in TB diagnosis and partial treatment success; however, more evidence is needed to assess its effects on other respiratory diseases, especially in wider sub-Saharan Africa.

Feasibility of conducting a randomised controlled trial of a cookstove intervention in rural Malawi.

BACKGROUND: Exposure to household air pollution (HAP) causes 4 million deaths annually, and strategies to reduce HAP exposure are urgently required. OBJECTIVE: To evaluate the acceptability and feasibility of conducting a trial of a cookstove intervention in rural Malawi. DESIGN: Non-smoking women were randomised to continuing to use an open fire (control) or to using a wood-burning clay cookstove (intervention). Symptom burden, oxygen saturation and exhaled carbon monoxide (eCO) were assessed at baseline and 7-day follow-up. A subset of women underwent HAP exposure monitoring. RESULTS: Of 51 women recruited, 50 (98%) completed the main study. The methodology was acceptable to participants. Headache, back pain and cough were the most commonly reported symptoms at baseline and follow-up. Median eCO was within normal limits, but with a difference of 0.5 parts per million (ppm) in median change of eCO from baseline to follow-up seen between the two groups (P = 0.035). The peak ambient CO concentration detected was 150 ppm. CONCLUSION: This study suggests that a large cookstove intervention trial in Malawi would be feasible with careful community sensitisation. Monitoring exposure to HAP is challenging, and further studies evaluating potential biomarkers of exposure, including eCO, should be undertaken.

Surveillance of tuberculosis in Malawian prisons.

SETTING: The Malawi National Tuberculosis Programme (NTP) has collaborated with the Prison Health Services (PHS) on tuberculosis (TB) control in prisons since 1996. Information on case finding and treatment outcomes is routinely collected, but there has not been any recent countrywide review of these prison data. OBJECTIVES: To determine 1) the number of prisoners registered for TB in 2007, 2) TB treatment outcomes in 2006 and 3) training of prison health care staff in all Malawian prisons. DESIGN: Descriptive study involving a review of 2006 and 2007 data collected by the NTP during surveillance in 2008. RESULTS: In 2007, 278 TB patients were registered in Malawian prisons, representing a TB case notification rate of 835 per 100 000 (higher than that in the general population, at 346/100 000). The treatment success rate for new smear-positive TB cases for 2006 was 73%, lower than the national average of 78%. In all, 52 prison health care staff had received 1 week of training in TB management, usually just after starting work in the prison. CONCLUSIONS: TB case notifications in Malawian prisons were higher than in the general population and treatment outcomes less favourable. The NTP and PHS need better collaboration to improve TB control in Malawian prisons.

Prevalence of smear-positive pulmonary tuberculosis among prisoners in Malawi: a national survey.

A cross-sectional cell-to-cell survey was conducted in 18 of 22 prisons in Malawi to determine the period prevalence of smear-positive pulmonary tuberculosis (PTB). In each prison, prisoners were interviewed using a structured questionnaire. Prisoners with cough of >1 week's duration were investigated by sputum smear examination. Of 7661 prisoners, 3887 had cough of > or =1 week, of whom 3794 submitted three sputum specimens: 54 (0.7%) had smear-positive PTB. The prevalence of PTB was higher in large urban prisons (1.1%) than in district prisons (0.3%, P < 0.001). More needs to be done to improve TB control in urban prisons.

Short communication: antituberculosis drug-induced hepatotoxicity is unexpectedly low in HIV-infected pulmonary tuberculosis patients in Malawi.

The proportion of patients with antituberculosis drug-induced hepatotoxicity (ATDH) was unexpectedly low during a trial on cotrimoxazole prophylaxis in Malawian HIV-positive pulmonary tuberculosis patients. About 2% of the patients developed grade 2 or 3 hepatotoxicity during tuberculosis (TB) treatment, according to WHO definitions. Data on ATDH in sub-Saharan Africa are limited. Although the numbers are not very strong, our trial and other papers suggest that ATDH is uncommon in this region. These findings are encouraging in that hepatotoxicity may cause less problem than expected, especially in the light of combined HIV/TB treatment, where drug toxicity is a major cause of treatment interruption.

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.

High mortality rates in tuberculosis patients in Zomba Hospital, Malawi, during 32 months of follow-up.

There is little information about long-term follow-up in patients with smear-negative pulmonary tuberculosis (PTB) or extrapulmonary tuberculosis (EPTB) who have been treated under routine programme conditions in sub-Saharan Africa. A prospective study was carried out to determine outcome 32 months from start of treatment in an unselected cohort of 827 adults TB inpatients registered at Zomba Hospital, Malawi, in 1 July-31 December 1995. By 32 months, 351 (42%) patients had died. Death rates were 30% (95% confidence interval [95% CI] 25-35%) in 386 patients with smear-positive PTB, 60% (95% CI 53-67%) in 211 patients with smear-negative PTB and 47% (95% CI 40-54%) in 230 patients with EPTB. Of the 793 patients with concordant HIV test results 612 (77%) were HIV seropositive: 47% HIV-positive patients were dead by 32 months compared with 27% HIV-negative patients (adjusted hazard ratio [HR] 2.3; 95% CI 1.7-3.1, P < 0.001). Smear-negative PTB patients had the highest death rates during the 32-month follow-up (HR 2.7; 95% CI 2.1-3.5, P < 0.001 compared to smear-positive patients), followed by EPTB patients (HR 1.9; 95% CI 1.5-2.5, P < 0.001 compared to smear-positive patients). When analysis was restricted to after the treatment period had finished (i.e., months 12-32), the differences in mortality were maintained for HIV-serostatus and for types of TB. Low-cost, easy to implement strategies for reducing mortality in HIV-positive TB patients in sub-Saharan Africa (such as the use of trimethoprim-sulphamethoxazole prophylaxis) need to be tested urgently in programme settings.

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.

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.

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.

Treatment outcome of an unselected cohort of tuberculosis patients in relation to human immunodeficiency virus serostatus in Zomba Hospital, Malawi.

There is little information about treatment outcome in patients with smear-negative pulmonary tuberculosis (PTB) or extrapulmonary tuberculosis (EPTB) treated under routine programme conditions in subsaharan Africa. A prospective study was carried out to determine treatment outcome in an unselected cohort of TB patients admitted to Zomba General Hospital, Malawi. Eight hundred and twenty-seven adult TB patients (451 men and 376 women) were registered between 1 July and 31 December 1995. Standardized treatment outcomes of treatment completion, death, default, and transfer to another district were assessed in relation to type of TB, human immunodeficiency virus (HIV) serostatus, age and gender. Two hundred and fifty-four patients (31%) died by the end of treatment, half of the deaths occurring in the first month. Death rates were 19% among 386 patients with smear-positive PTB, 46% among 211 patients with smear-negative PTB, and 37% among 230 patients with EPTB; 77% of the patients were HIV seropositive. Among new patients, HIV-positive patients had higher death rates than HIV-negative patients (hazard ratio [HR] 2.5; 95% confidence interval [95% CI] 1.6-3.8). Smear-negative patients had the highest death rates (HR 3.9; 95% CI 2.7-5.5 compared to smear-positive patients), followed by EPTB patients (HR 2.6, 95% CI 1.8-3.7 compared to smear-positive patients). Death rates increased with age but were similar in men and women. Adult patients in Malawi with smear-negative PTB and EPTB have low treatment completion and high death rates, related to high levels of HIV infection. National TB control programmes in areas of high HIV prevalence should no longer ignore treatment outcomes in patients with smear-negative PTB or EPTB.

Management of pulmonary tuberculosis suspects with negative sputum smears and normal or minimally abnormal chest radiographs in resource-poor settings.

SETTING: Queen Elizabeth Central Hospital, Blantyre, Malawi. OBJECTIVES: 1) To determine the proportion of pulmonary tuberculosis (PTB) suspects with negative sputum smears and a normal/minimally abnormal chest radiograph (CXR) who are culture-positive for Mycobacterium tuberculosis, and 2) to determine how many develop smear or radiographic evidence of PTB (TB CXR) during follow-up. METHODS: PTB suspects with negative sputum smears and a normal/minimally abnormal CXR were given a second course of antibiotics and followed up at 3-week intervals over 3 months with repeat sputum smears and chest radiography. RESULTS: Of 79 patients (38 men and 41 women, mean age 33 years) with negative smears and a normal/minimally abnormal CXR, 16 (21%) were culture-positive for M. tuberculosis. Of 15 culture-positive patients who were alive and attended follow-up, seven (47%) developed a TB-CXR by 3 months. Of 41 culture-negative patients who were alive and attended follow-up, 13 (32%) developed a TB-CXR, including one patient who became sputum smear-positive. TB-CXRs were found only in patients with a cough. CONCLUSION: TB suspects with negative smears and normal/minimally abnormal CXRs in high human immunodeficiency virus (HIV) prevalent countries should be given a second course of antibiotics. If cough improves, patients can be advised not to return for further follow-up. If cough continues, patients should return for further follow-up with sputum smear examination and chest radiography. Approximately 50% of those who have culture-positive PTB will develop a TB-CXR by 3 months and can be identified if radiographic facilities are available.

Prevalence of tuberculosis in TB suspects with short duration of cough.

The prevalence of pulmonary tuberculosis (PTB) in patients with short duration of cough was determined. Ninety-eight adult out-patients (60 men, 38 women; mean age 32 years) at Queen Elizabeth Central Hospital, Blantyre, Malawi, who had cough for 1-3 weeks which was unresponsive to a course of antibiotics, were successfully screened by microscopy and culture of 2 or 3 sputum specimens and chest radiography; 34 (35%) had PTB. Ten patients were sputum smear-positive and 24 were smear-negative and culture-positive. There was no difference in age, gender or clinical features of general illness, respiratory disease and HIV-related disease between patients with PTB and those with no evidence of PTB. Nine patients (26%) with microbiologically confirmed tuberculosis (TB) had chest radiograph abnormalities consistent with TB, compared with 5 (8%) of patients with no microbiological evidence of TB. Certain classes of patients with a short history of cough would benefit from PTB screening strategies with the emphasis on sputum examination rather than chest radiography, which is unreliable in such patients. The classes include (i) patients with other features of TB whose cough has not improved with antibiotic therapy, (ii) seriously ill patients, and (iii) patients in high risk institutions such as prisons and refugee camps.

Tuberculous meningitis. Short course of chemotherapy.

In March 1986, we began a 6-month short course trial of therapy for tuberculous meningitis, in which 28 patients were analyzed. The diagnosis was based on the following cerebrospinal fluid test results: in 53.5% of the cases, Mycobacterium tuberculosis was identified by direct smear; in 57%, culture in Löwenstein-Jensen medium was positive; in 83.3%, the detection of anti-bacille Calmette-Guérin (BCG) antibodies by enzyme-linked immunosorbent assay was positive; and in 74%, the dosification of adenosine deaminase activity was positive. In addition, in 21.4% of the cases, the diagnosis was established by means of autopsy findings. Moreover, the diagnosis was supported by bacteriological analyses from another tissue or body fluids. Despite the administration of an antituberculous therapy, 32.4% of the patients died: all of the decreased had reached the last stage of the disease by the beginning of treatment. Sixteen percent of the patients who survived after more than 18 months of follow-up after therapy had ended suffered neurological sequelae. With the 6-month therapeutic regimen, the morbidity/mortality is similar to that found in the longer-course therapies. The latter regimen is therefore thought to be a good and acceptable therapeutic option for the treatment of tuberculous meningitis.

Faecal mycobacteria and their relationship to HIV-related enteritis in Lusaka, Zambia.

The prevalence of infection with mycobacteria, both typical and atypical, is increasing along with prevalence of infection with HIV. Patients with pulmonary tuberculosis (PTB) and patients with chronic diarrhoea are forming a growing proportion of the patient population in hospitals in central Africa. To investigate the possibility that mycobacteria may be responsible for some of the HIV-related enteropathy seen in Lusaka, we studied 89 patients in four different diagnostic groups, clinically, by Mantoux test and by microscopy and culture of stool specimens for mycobacteria. In the HIV-positive group with chronic diarrhoea (n = 31), two patients were found to have mycobacteria on faecal smear and three were culture positive while of the 15 HIV-negative controls, three were smear positive and three were culture positive. Of the 15 patients with proven PTB, three had positive faecal smears but none were culture positive. In the fourth group of 24 patients with suspected PTB, seven were smear positive and five, culture positive. Only in this last group was there some correlation between smear results and culture results. Although this last finding is difficult to explain, it appears that there is no correlation between the symptom of chronic diarrhoea and the presence of mycobacteria in the stool. We conclude that mycobacteria do not play a significant role in the pathogenesis of HIV-related enteropathy in Lusaka.