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 to determine i) whether faecal Escherichia coli (E.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 co-trimoxazole), 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 anticipated from the use of co-trimoxazole prophylaxis in preventing non-typhoidal salmonella bacteraemia and enteritis in HIV infected TB patients in Malawi.     

Tuberculosis in health care workers in a central hospital in Malawi.

A retrospective study was carried out at Lilongwe Central Hospital, Malawi, to determine 1) the tuberculosis case notification rate in health care workers (HCW) in 2001, and 2) whether NTP guidelines were adhered to in diagnosing TB. Of 571 HCWs, 33 (6%) were notified with TB in 2001, giving a TB case notification rate of 5780/100,000. Patient attendants had higher rates of TB than nurses, ward attendants and doctors, but otherwise there were no significant differences between the HCW categories. NTP diagnostic guidelines were not properly followed, particularly in diagnosing smear-negative TB; in HCWs with smear-negative PTB, 64% had no sputum smears examined. The rate of TB in HCWs in a central hospital in Malawi was high, although lack of adherence to guidelines might have resulted in overdiagnosis.     

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.     

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.     

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.