Does antiretroviral treatment reduce case fatality among HIV-positive patients with tuberculosis in Malawi?

SETTING: Thyolo district, Malawi. OBJECTIVES: To report on 1) case fatality among human immunodeficiency virus (HIV) positive tuberculosis (TB) patients while on anti-tuberculosis treatment and 2) whether antiretroviral treatment (ART) initiated during the continuation phase of TB treatment reduces case fatality. DESIGN: Retrospective cohort analysis. METHODS: Comparative analysis of treatment outcomes for TB patients registered between January and December 2004. RESULTS: Of 983 newly registered TB patients receiving diagnostic HIV testing, 658 (67%) were HIV-positive. A total of 132 (20%) patients died during the 8-month course of anti-tuberculosis treatment, of whom 82 (62%) died within the first 2 months of treatment when ART was not provided (cumulative incidence 3.0, 95%CI 2.5-3.6 per 100 person-years). A total of 576 TB patients started the continuation phase of anti-tuberculosis treatment, 180 (31%) of whom were started on ART. The case-fatality rate per 100 person-years was not significantly different for patients on ART (1.0, 95%CI 0.6-1.7) and those without ART (1.2, 95%CI 0.9-1.7, adjusted hazard ratio 0.86, 95%CI 0.4-1.6, P = 0.6) CONCLUSIONS: ART provided in the continuation phase of TB treatment does not have a significant impact on reducing case fatality. Reasons for this and possible measures to reduce high case fatality in the initial phase of TB treatment are discussed.

Developing a socio-economic measure to monitor access to tuberculosis services in urban Lilongwe, Malawi.

OBJECTIVES: To develop locally appropriate measures of poverty for the National Tuberculosis Programme (NTP), Malawi, and to assess access to tuberculosis (TB) services by different socio-economic groups by establishing a socio-economic profile of current TB patients DESIGN: A quantitative proxy measure of poverty was developed through regression analysis of data from the 1998 national Malawi Integrated Household Survey. A qualitative assessment of poverty was conducted in poor and non-poor settlements in urban Lilongwe to identify key indicators of socio-economic status. Both quantitative and qualitative indicators were used to assess the socioeconomic status of 179 TB patients who participated in a cross-sectional survey. FINDINGS: The proxy measure of poverty and the qualitative indicators demonstrated similar ability to measure the poverty status of patients. The poverty head count among patients using the quantitative and qualitative indicators were 78% and 70%, respectively. Geographical analysis showed that 60% were from non-poor areas and only 15% (26/139) were from squatter settlements. CONCLUSION: This study established a strategy for monitoring access to TB services using a proxy measure of poverty and qualitative indicators. This is a vital first step in developing an evidence base for pro-poor equitable TB services.

Can we get more HIV-positive tuberculosis patients on antiretroviral treatment in a rural district of Malawi?

The World Health Organization (WHO) has set a target of treating 3 million people with antiretroviral treatment (ART) by 2005. In sub-Saharan Africa, HIV-positive tuberculosis (TB) patients could significantly contribute to this target. ART (stavudine/lamivudine/nevirapine) was initiated in Thyolo district, Malawi, in April 2003, and all HIV-positive TB patients were considered eligible and offered ART. Despite this, only 44 (13%) of 352 TB patients were eventually started on ART by the end of November 2003. Most TB patients leave hospital after 2 weeks to complete the initial phase of anti-tuberculosis treatment (rifampicin-based) in the community, and ART is offered to HIV-positive TB patients after they have started the continuation phase of treatment (isoniazid/ ethambutol). ART is only offered at hospital, while the majority of TB patients take their continuation phase of anti-tuberculosis treatment from health centres. HIV-positive TB patients therefore find it difficult to access ART. In this paper, we discuss a series of options to increase the uptake of ART among HIV-positive TB patients. The main options are: 1) to hospitalise HIV-positive TB patients with a view to starting ART in the continuation phase in hospital; 2) to decentralise ART delivery so ART can be delivered at health centres; 3) to replace nevirapine with efavirenz so ART can be started earlier in the initial phase of anti-tuberculosis treatment. Decentralisation of ART from hospitals to health centres would greatly improve ART access.

WHO clinical staging of HIV infection and disease, tuberculosis and eligibility for antiretroviral treatment: relationship to CD4 lymphocyte counts.

SETTING: Thyolo district, Malawi. OBJECTIVES: To determine in HIV-positive individuals aged over 13 years CD4 lymphocyte counts in patients classified as WHO Clinical Stage III and IV and patients with active and previous tuberculosis (TB). DESIGN: Cross-sectional study. METHODS: CD4 lymphocyte counts were determined in all consecutive HIV-positive individuals presenting to the antiretroviral clinic in WHO Stage III and IV. RESULTS: A CD4 lymphocyte count of < or = 350 cells/microl was found in 413 (90%) of 457 individuals in WHO Stage III and IV, 96% of 77 individuals with active TB, 92% of 65 individuals with a history of pulmonary TB (PTB) in the last year, 91% of 89 individuals with a previous history of PTB beyond 1 year, 81% of 32 individuals with a previous history of extra-pulmonary TB, 93% of 107 individuals with active or past TB with another HIV-related disease and 89% of 158 individuals with active or past TB without another HIV-related disease. CONCLUSIONS: In our setting, nine of 10 HIV-positive individuals presenting in WHO Stage III and IV and with active or previous TB have CD4 counts of < or = 350 cells/microl. It would thus be reasonable, in this or similar settings where CD4 counts are unavailable for clinical management, for all such patients to be considered eligible for antiretroviral therapy.

'Lost' smear-positive pulmonary tuberculosis cases: where are they and why did we lose them?

SETTING: Ntcheu District, rural Malawi. OBJECTIVES: 1) To locate smear-positive pulmonary tuberculosis patients who were identified during the first 6 months of 2000 but did not start treatment ('lost cases'); 2) to describe these patients' pathways to diagnosis, health status and socio-demographic characteristics; and 3) to explore why these patients did not start treatment. METHODS: Lost cases were traced from programme registers and interviewed using the qualitative research critical incidents narrative (CIN) interviews technique. Results were triangulated with responses from health care workers through focus group discussions. RESULTS: The laboratory registered 157 new smear-positive patients. Twenty three (15%) of these were 'lost' (did not appear in the treatment register). CIN interviews were conducted with five lost patients and 14 carers of lost patients who had died. Long pathways to diagnosis were the norm. Health system structural barriers were the main factors behind these pathways, including requirement for hospital attendance, delays in symptom recognition and receipt of sputum results, and the misconception that negative smears excluded tuberculosis. CONCLUSION: Some smear-positive cases experience very long pathways to diagnosis and are lost from this free public health system. The diagnostic process needs to become more responsive to patients' needs.

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.

Risk of infection with Mycobacterium tuberculosis in Malawi: national tuberculin survey 1994.

OBJECTIVE: To estimate the annual risk of tuberculosis infection among schoolchildren in Malawi. METHODS: A school survey was conducted in twelve randomly selected districts in Malawi. Children in standard 1-4 and aged 6-11 years were eligible. Tuberculin skin testing was performed according to World Health Organization/International Union Against Tuberculosis and Lung Disease guidelines. RESULTS: Of the 17123 eligible children, 80% were tested. Of those tested 79% were read. The prevalence of infection according to various criteria was 9-12% in children without bacille Calmette-Guerin (BCG) scar. The prevalence of reactions of 10 mm or more was lower in girls than in boys, increased with age, and was higher in those with than in those without BCG scar. The annual risk of infection was estimated to be within the range 0.6-1.4%. CONCLUSION: Annual risk of infection in Malawi was in the order of 1%. This study is expected to provide valuable baseline information for an assessment of the impact of human immunodeficiency virus (HIV) on tuberculosis transmission in Malawi.

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.

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.

Moderate to severe malnutrition in patients with tuberculosis is a risk factor associated with early death.

A study was conducted in new patients registered with tuberculosis (TB) in a rural district of Malawi to determine (i) the prevalence of malnutrition on admission and (ii) the association between malnutrition and early mortality (defined as death within the first 4 weeks of treatment). There were 1181 patients with TB (576 men and 605 women), whose overall rate of infection with human immunodeficiency virus (HIV) was 80%. 673 TB patients (57%) were malnourished on admission (body mass index [BMI] < 18.5 kg/m2). There were 259 patients (22%) with mild malnutrition (BMI 17.0-18.4 kg/m2), 168 (14%) with moderate malnutrition (BMI 16.0-16.9 kg/m2) and 246 (21%) with severe malnutrition (BMI < 15.9 kg/m2). 95 patients (8%) died during the first 4 weeks. Significant risk factors for early mortality included increasing degrees of malnutrition, age > 35 years, and HIV seropositivity. Among all the 1181 patients, 10.9% of the 414 patients with moderate to severe malnutrition died in the first 4 weeks compared with 6.5% of the 767 patients with normal to mild malnutrition (odds ratio 1.8, 95% confidence interval 1.1-2.7). In patients with TB, BMI < 17.0 kg/m2 is associated with an increased risk of early death.

Changes in Escherichia coli resistance to co-trimoxazole in tuberculosis patients and in relation to co-trimoxazole prophylaxis in Thyolo, Malawi.

In Thyolo district, Malawi, an operational research study is being conducted on the efficacy and feasibility of co-trimoxazole prophylaxis in preventing deaths in HIV-positive patients with tuberculosis (TB). A series of cross-sectional studies were carried out in 1999 and 2001 to determine (i) whether faecal Escherichia coli resistance to co-trimoxazole in TB patients changed with time, and (ii) whether the resistance pattern was different in HIV-positive TB patients who were taking co-trimoxazole prophylaxis. Co-trimoxazole resistance among E. coli isolates in TB patients at the time of registration was 60% in 1999 and 77% in 2001 (P < 0.01). Resistance was 89% among HIV-infected TB patients (receiving cotrimoxazole), while in HIV-negative patients (receiving anti-TB therapy alone) it was 62% (P < 0.001). The study shows a significant increase of E. coli resistance to co-trimoxazole in TB patients which is particularly prominent in HIV-infected patients on co-trimoxazole prophylaxis. Since a high degree of plasmid-mediated transfer of resistance exists between E. coli and the Salmonella species, these findings could herald limitations on the short- and long-term benefits to be expected from the use of co-trimoxazole prophylaxis in preventing non-typhoid Salmonella bacteraemia and enteritis in HIV-infected TB patients in Malawi.

Factors contributing to a successful tuberculosis control programme in Malawi

A discription of the revised National Tuberculosis Programme [NTP] and the reasons for the continued improvement from year to year despite the relatively small number of core tuberculosis personnel. These factors include: political stability; pragmatic governmental policies; self-sufficiency in food; standardized tuberculosis control strategies; constant staff training and supervision; and community participation

Malawi national TB programme: report on evaluation of TB treatment; 1st quarter; April; 1989

The results of 558 patients enrolled by the National Tuberculosis Programme [NTP] on Short Course Chemotherapy under routine conditions were satisfactory with 82 percent reporting negative at the end