Multidrug- and isoniazid-resistant tuberculosis in three high HIV burden African regions.

SETTING: Despite major progress in the surveillance of drug-resistant tuberculosis (TB), data are lacking for many low-resource countries. World Health Organization estimates of multidrug-resistant TB (MDR-TB) rates in Africa are low, and based on very limited data from the African continent. OBJECTIVE: To measure MDR-TB prevalence in sub-Saharan African regions with a high prevalence of human immunodeficiency virus (HIV). METHOD: We conducted three anti-tuberculosis drug resistance surveys in sub-Saharan African regions with high HIV-TB coinfection prevalence: Homa Bay (Kenya), Chiradzulu (Malawi) and West Nile region (Uganda). RESULTS: The prevalence of MDR-TB in new patients was found to be low in the three regions: 1.4% (95%CI 0.2-2.6) in Homa Bay, 2.0% (95%CI 0.4-3.6) in Chiradzulu and 0.6% (95%CI 0.0-1.5) in the West Nile region. We found no significant association between MDR-TB and HIV infection. Nonetheless, ≥ 10% of the new cases surveyed were resistant to isoniazid (INH). CONCLUSION: The relatively high rate of resistance to INH highlights the need for rapid detection of INH resistance in addition to rifampicin (RMP) resistance, to allow rapid modification of treatment to avoid the acquisition of RMP resistance. Drug resistance should be monitored periodically.

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.

Developing Research Partnerships to Bring Change : Experiences from REACH Trust Malawi

Drawing on the experiences of REACH Trust; this paper highlights practical lessons of using research processes and outcomes to promote equity in health policy and practice. The REACH Trust is first introduced. Case studies are then used to highlight how REACH Trust has worked in a participatory manner with key stakeholders at community; national and international levels. In addition to participatory working there are a number of cross-cutting themes that facilitate the uptake of research findings which is discussed in turn: (1) multi-disciplinary and multi-method approaches (2) advocating research findings at strategic forums; and (3) the use of strategic frames. In the conclusion it is argued that research has a critical role to play in responding to the urgent need for the Malawian health sector to develop and act on evidence-based practice in a more gender equitable and pro-poor manner

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.

Scaling up antiretroviral therapy in Africa: learning from tuberculosis control programmes--the case of Malawi.

The rapid and massive scale-up of antiretroviral drug therapy (ART) so needed in sub-Saharan Africa will not be possible using a 'medicalised' model. A more simple approach is required. DOTS has been used now for many years to provide successful anti-tuberculosis treatment to millions of patients in poor countries of the world, and many of the established concepts can be used for the delivery of ART. Malawi, a small and impoverished country in sub-Saharan Africa, is embarking on a national scale-up of ART. In this review we describe how we have adopted several of the principles of DOTS for delivering ART in Malawi: case finding and registration, treatment, monitoring, drug procurement, staffing and the issue of free drugs. We also discuss ART for HIV-infected TB patients. We hope that by using the DOTS approach we will be able to deliver ART to large numbers of HIV-infected patients under controlled conditions, and minimise the risk of developing drug resistance.

Scaling up HIV/AIDS and joint HIV-TB services in Malawi.

Two country-wide surveys were undertaken to assess progress in scaling up human immunodeficiency virus/ acquired immune-deficiency syndrome (HIV/AIDS) and HIV-tuberculosis (TB) services in the public health sector in Malawi between 2002 and 2003. In 2003, 118 sites were performing counselling and HIV testing compared with 70 in 2002. There were 215 269 HIV tests carried out in 2003 compared with 149 540 in 2002, the largest increases being in pregnant women (from 5059 to 26791), patients with TB (from 2130 to 3983) and patients/clients attending health facilities (from 35 407 to 79 584). In 2003, 3703 patients with AIDS were started on antiretroviral therapy compared with 1220 patients in 2002.

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.

Human resources for control of tuberculosis and HIV-associated tuberculosis.

The global targets for tuberculosis (TB) control were postponed from 2000 to 2005, but on current evidence a further postponement may be necessary. Of the constraints preventing these targets being met, the primary one appears to be the lack of adequately trained and qualified staff. This paper outlines: 1) the human resources and skills for global TB and human immunodeficiency virus (HIV) TB control, including the human resources for implementing the DOTS strategy, the additional human resources for implementing joint HIV-TB control strategies and what is known about human resource gaps at global level; 2) the attempts to quantify human resource gaps by focusing on a small country in sub-Saharan Africa, Malawi; and 3) the main constraints to human resources and their possible solutions, under six main headings: human resource planning; production of human resources; distribution of the work-force; motivation and staff retention; quality of existing staff; and the effect of HIV/AIDS. We recommend an urgent shift in thinking about the human resource paradigm, and exhort international policy makers and the donor community to make a concerted effort to bridge the current gaps by investing for real change.

Performance-related allowances within the Malawi National Tuberculosis Control Programme.

SETTING: National Tuberculosis (TB) Control Programme (NTP), Malawi. OBJECTIVES: To determine the feasibility and effectiveness of performance-related allowances for NTP personnel working at central and regional levels in Malawi. In particular, to determine 1) whether programme staff can complete 6-monthly self-assessment forms related to the tasks they are expected to perform during that period, and 2) whether the NTP can achieve four key programme targets related to case finding, treatment outcome and the sending of sputum specimens for drug resistance monitoring. DESIGN: A descriptive study. RESULTS: For January to June 2003, 25 personnel completed self-assessment forms, and in all cases individual performance was judged satisfactory. For July to December 2003, 21 personnel completed self-assessment forms, and in 20 cases individual performance was judged satisfactory. In the first quarter of 2003, only one target was achieved for the country, and NTP personnel were awarded one quarter of the performance payment. In the third quarter, two targets were achieved and NTP personnel were awarded one half of the performance payment. CONCLUSION: It is feasible to implement performance-related payments for NTP personnel. Ways to routinely introduce such a system for NTP and other staff in the health sector urgently need to be explored.

'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.

Childhood tuberculosis in Malawi: caseload, diagnostic practices and treatment outcomes.

There were 22,982 cases of TB registered in Malawi in 1998, of which 2739 (11.9%) were children. Children accounted for 11.3% of all case notifications with smear-positive pulmonary TB (PTB), 21.3% with smear-negative PTB and 15.9% with extrapulmonary TB (EPTB). A significantly higher proportion of TB cases were diagnosed in central hospitals. Only 45% of children completed treatment. There were high rates of death (17%), default (13%) and unknown treatment outcomes (21%). Treatment outcomes were worse in younger children and in children with smear-negative PTB. In 2001, all 44 non-private hospitals in Malawi that register and treat children with tuberculosis (TB) were surveyed to determine actual diagnostic practice. This cross sectional study identified 150 children aged 14 years or below in hospital receiving anti-TB treatment, 98 with pulmonary TB (PTB) and 52 with extrapulmonary TB (EPTB). Median duration of illness was 8 weeks. Most patients had fever, no response to anti-malarial treatment and antibiotics, and 40% had a positive family history of TB. Nearly 45% had weight for age < 60%. Diagnosis was mainly based on clinical features and radiography, with less than 10% having tuberculin skin tests or HIV serology, and very few having other sophisticated investigations. Diagnostic difficulties make it difficult to accurately define the actual burden of childhood TB in Malawi. Diagnostic practices are poor and treatment outcomes unsatisfactory.

Geographical Information Systems in TB control

Geographical Information Systems (GIS) is becoming a useful tool in disease control by health planners. However little is known about its potential in tuberculosis (TB) control. In 2000 the National TB Programme (NTP) in Malawi assessed its usefulness. Routinely collected case-finding data from the 3 previous years (1997 to 1999) were entered into a system containing a digital map of Malawi. District performance was mapped. We concluded that GIS may be complementary in monitoring TB programme performance; and may be useful for target setting; advocacy; and research. World Health Organisation (WHO) now provides free GIS software (Health Mapper) and training. However; the use of GIS in TB control still needs further piloting and expansion without constraining the locally available resources or disrupting the present TB data management system

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.

Counselling, HIV testing and adjunctive cotrimoxazole for TB patients in Malawi: from research to routine implementation.

SETTING: Fifteen hospitals in Malawi that offer voluntary counselling and testing (VCT) for the human immunodeficiency virus (HIV) for tuberculosis (TB) patients and cotrimoxazole (CTX) for patients found to be HIV-positive. OBJECTIVES: 1) To describe the process of developing a national TB-HIV plan, conducting a country-wide situational assessment, and producing national guidelines on VCT and CTX for TB patients, and 2) to assess the implementation of VCT and CTX for TB patients registered between July and September 2003. DESIGN: A descriptive study. RESULTS: The 3-year HIV-TB plan was finalised in 2002. Between January and March 2003, an assessment was carried out of HIV/AIDS and joint HIV-TB services in Malawi and a decision made to support 15 hospitals in implementing VCT and CTX for TB patients. Between April and June 2003, national guidelines on VCT and CTX were developed through a consultative process, and treatment units were prepared for implementation. Between July and September 2003, 2397 TB patients were registered, and 1404 (59%) accepted VCT; 956 (68%) were HIV-positive, of whom 927 (97%) started CTX. Deficiencies in the registration process and in patient understanding about VCT and CTX were identified. CONCLUSION: The results show that it is feasible to routinely implement VCT and CTX for TB patients.

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.

Prescriptions and dosages of anti-tuberculosis drugs in the National Tuberculosis Control Programme of Malawi.

SETTING: All 44 non-private hospitals in Malawi treating pulmonary tuberculosis (PTB) patients with an oral regimen (0.5RHZE/1.5R3H3Z3E3/6HE). OBJECTIVES: In new smear-positive PTB patients, to determine whether: 1) numbers of tablets were correctly prescribed according to pre-treatment weights, and 2) medication dosages were adequate, too low or too high. DESIGN: Retrospective review of TB registers and TB treatment cards for patients registered with new smear-positive PTB between 1 October and 31 December 2001. RESULTS: Of 1970 patients aged > or = 15 years, 1211 (62%) had treatment cards and pre-treatment weights. Incorrect prescriptions were given to 88 (7%), and many of these received dosages of anti-tuberculosis drugs that were too high or too low. For those receiving correct prescriptions, daily treatment in the initial and continuation phases was generally associated with adequate dosages of drugs. However, in the initial intermittent phase, between 3% and 40% of patients received anti-tuberculosis drug dosages that were too low. CONCLUSION: A small percentage of patients receive incorrect prescriptions, which can be resolved by training and supervision. In those receiving correct prescriptions, intermittent treatment provides dosages that are sometimes too low. Weight bands for intermittent treatment should be re-examined.