Reduced tuberculosis case notification associated with scaling up antiretroviral treatment in rural Malawi.

OBJECTIVE: To report on the trends in new and recurrent tuberculosis (TB) case notifications in a rural district of Malawi that has embarked on large-scale roll-out of antiretroviral treatment (ART). METHODS: Descriptive study analysing TB case notification and ART enrolment data between 2002 and 2009. RESULTS: There were a total of 10,070 new and 755 recurrent TB cases. ART scale-up started in 2003, and by 2007 an estimated 80% ART coverage had been achieved and was sustained thereafter. For new TB cases, an initial increase in case notifications in the first years after starting ART (2002-2005) was followed by a highly significant and sustained decline from 259 to 173 TB cases per 100,000 population (χ(2) for trend 261, P < 0.001, cumulative reduction for 2005-2009 = 33%, 95%CI 27-39). For recurrent TB, the initial increase was followed by a significant drop, from 20 to 15 cases/100,000 (χ(2) for linear trend = 8.3, P = 0.004, constituting a 25% (95%CI 9-49) cumulative reduction between 2006 and 2009. From 2005 to 2009, ART averted an estimated 1164 (95%CI 847-1480) new TB cases and 78 (95%CI 23-151) recurrent TB cases. CONCLUSIONS: High ART implementation coverage is associated with a very significant declining trend in new and recurrent TB case notifications at population level.

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.

Voluntary counselling, HIV testing and adjunctive cotrimoxazole are associated with improved TB treatment outcomes under routine conditions in Thyolo District, Malawi.

SETTING: Two rural districts in Malawi: Thyolo, where voluntary counselling and human immunodeficiency virus (HIV) testing (VCT) is offered to all tuberculosis (TB) patients and adjunctive cotrimoxazole to HIV positives, and Mulanje, where no such interventions are offered. OBJECTIVES: For all TB patients registered in 2001: 1) to determine the uptake of VCT and cotrimoxazole in Thyolo, and 2) to compare treatment outcomes between Thyolo and Mulanje. DESIGN: A cohort study using routinely collected programme data. RESULTS: There were 1239 TB patients in Mulanje and 1103 in Thyolo. In Thylo, 1064 (97%) patients consented to VCT, 1006 were HIV tested (91%) and 761 (69%) were started on cotrimoxazole a median of 4 days from registration; 77% of patients tested in Thyolo were HIV-positive. For all TB patients, in Thyolo and Mulanje, treatment success was respectively 75% and 61% (P < 0.001); death was 21% and 25% (P = 0.026); and other outcomes were 4% and 14% (P < 0.001). The adjusted relative risks of treatment success (1.23), death (0.84) and other outcomes (0.26) in Thyolo were significantly different from those in Mulanje (P < 0.001). CONCLUSION: VCT and adjunctive cotrimoxazole is well accepted by TB patients in Thyolo and, with other HIV care and support services, is associated with good treatment outcome indicators for the National Tuberculosis Programme. This intervention is being expanded to other districts in Malawi, and other African countries should consider a similar approach to the dual HIV-TB epidemic.

Passive versus active tuberculosis case finding and isoniazid preventive therapy among household contacts in a rural district of Malawi.

SETTING: Thyolo district, rural Malawi. OBJECTIVES: To compare passive with active case finding among household contacts of smear-positive pulmonary tuberculosis (TB) patients for 1) TB case detection and 2) the proportion of child contacts aged under 6 years who are placed on isoniazid (INH) preventive therapy. DESIGN: Cross-sectional study. METHODS: Passive and active case finding was conducted among household contacts, and the uptake of INH preventive therapy in children was assessed. RESULTS: There were 189 index TB cases and 985 household contacts. Human immunodeficiency virus (HIV) prevalence among index cases was 69%. Prevalence of TB by passive case finding among 524 household contacts was 0.19% (191/100000), which was significantly lower than with active finding among 461 contacts (1.74%, 1735/100000, P = 0.01). Of 126 children in the passive cohort, 22 (17%) received INH, while in the active cohort 25 (22%) of 113 children received the drug. Transport costs associated with chest X-ray (CXR) screening were the major reason for low INH uptake. CONCLUSIONS: Where the majority of TB patients are HIV-positive, active case finding among household contacts yields nine times more TB cases and is an opportunity for reducing TB morbidity and mortality. The need for a CXR is an obstacle to the uptake of INH prophylaxis.

Cotrimoxazole prophylaxis in HIV-infected individuals after completing anti-tuberculosis treatment in Thyolo, Malawi.

SETTING: Thyolo, rural southern Malawi. OBJECTIVES: To determine 1) the proportion who continue with cotrimoxazole prophylaxis for the prevention of opportunistic infections, and 2) the reasons for continuing or stopping prophylaxis, in human immunodeficiency virus (HIV) infected individuals with tuberculosis (TB) who complete anti-tuberculosis treatment. DESIGN: A cross-sectional study. METHODS: A questionnaire study of all HIV-infected TB patients who had been registered over a 3-month period to receive anti-tuberculosis treatment and cotrimoxazole prophylaxis and who had completed antituberculosis treatment 3-6 months earlier. RESULTS: Of 82 HIV-infected individuals who were alive at the time of interview, 76 (93%) were continuing with cotrimoxazole and wished to do so indefinitely. The most common reason for continuing the drug was to prevent illness associated with HIV, while the most common reason for stopping was long distances to the health facility. Ninety-six percent of patients received cotrimoxazole free of charge from a health centre. Of those who wished to continue indefinitely, the majority (63%) could not afford to pay for the drug. CONCLUSIONS: In a rural setting, the great majority of HIV-infected individuals continued with cotrimoxazole after completing anti-tuberculosis treatment. Making the drug available and providing it free of charge is essential if it is to remain accessible for longer term prevention.

Compliance with cotrimoxazole prophylaxis for the prevention of opportunistic infections in HIV-positive tuberculosis patients in Thyolo district, Malawi.

OBJECTIVE: To verify compliance with cotrimoxazole prophylaxis in human immunodeficiency virus (HIV) infected tuberculosis (TB) patients during the continuation phase of anti-tuberculosis treatment, and to assess the sensitivity, specificity and positive predictive values of verbal verification and pill counts as methods of checking compliance. DESIGN: Cross-sectional study. METHODS: Cotrimoxazole compliance was assessed in a cohort of TB patients who were attending four TB follow-up centres during the continuation phase of anti-TB treatment between months 4 and 6. Verbal verification of drug intake, physical verification of pill count balance, and urine trimethoprim detection by gas chromatography and mass spectrometry were used for assessing compliance. RESULTS: Using urine trimethoprim detection as the gold standard for compliance, trimethoprim was detected in 82 (94%) of 87 patients in the cohort. Verbal verification of cotrimoxazole intake and objective pill count balances showed high sensitivity and positive predictive values compared with the gold standard of urine trimethoprim detection. CONCLUSIONS: In a rural district in Malawi, compliance with cotrimoxazole as an adjunct to anti-tuberculosis treatment in HIV-infected TB patients was good, and can be assessed simply and practically by verbal verification and pill counts.