The effect of HIV and antiretroviral therapy on characteristics of pulmonary tuberculosis in northern Malawi: a cross-sectional study.

BACKGROUND: HIV infection reduces the likelihood that individuals with pulmonary tuberculosis are smear positive and that they have cavitatory disease. Antiretroviral therapy (ART) may shift the pattern of disease to be more similar to that of HIV negative patients. This would aid diagnosis--which often depends on sputum smears--but would also increase infectiousness. We assessed the effect of HIV and ART on smear positivity and cavitatory disease in laboratory-confirmed pulmonary TB patients. METHODS: Three sputum samples were collected per pulmonary TB suspect and were examined using microscopy and culture. Chest radiographs were available for a subset of patients as part of another study. The effect of HIV and ART status on sputum smear positivity and lung cavitation were evaluated using multivariable logistic regression. RESULTS: Of 1024 laboratory-confirmed pulmonary TB patients who were identified between January 2005 and December 2011, 766 had HIV and ART status available. Positive sputum smears were significantly more common among HIV negative individuals than HIV positive individuals (adjusted OR = 2.91, 95% CI 1.53-5.55). Compared to those HIV positive but not on ART, patients on ART were more likely to be smear positive (adjusted OR = 2.33, 95% CI 1.01-5.39) if they had been on ART ≤ 6 months, but only slightly more likely to be smear positive (adjusted OR = 1.43, 95% CI 0.68-2.99) if they were on ART > 6 months. HIV negative patients were more likely than HIV positive patients to have cavitatory disease (adjusted OR = 1.97, 95% CI 1.20-3.23). Patients on ART > 6 months had a slight increase in cavitatory disease compared to HIV positive patients not on ART (adjusted OR = 1.68, CI 0.78-3.63). CONCLUSIONS: HIV infection is associated with less smear positivity and cavitation in pulmonary TB patients. Among HIV positive patients, the use of ART shifts the presentation of disease towards that seen in HIV-negative individuals, which facilitates diagnosis but which also could increase infectiousness

Whole Genome Sequencing Shows a Low Proportion of Tuberculosis Disease Is Attributable to Known Close Contacts in Rural Malawi.

BACKGROUND: The proportion of tuberculosis attributable to transmission from close contacts is not well known. Comparison of the genome of strains from index patients and prior contacts allows transmission to be confirmed or excluded. METHODS: In Karonga District, Malawi, all tuberculosis patients are asked about prior contact with others with tuberculosis. All available strains from culture-positive patients were sequenced. Up to 10 single nucleotide polymorphisms between index patients and their prior contacts were allowed for confirmation, and ≥ 100 for exclusion. The population attributable fraction was estimated from the proportion of confirmed transmissions and the proportion of patients with contacts. RESULTS: From 1997-2010 there were 1907 new culture-confirmed tuberculosis patients, of whom 32% reported at least one family contact and an additional 11% had at least one other contact; 60% of contacts had smear-positive disease. Among case-contact pairs with sequences available, transmission was confirmed from 38% (62/163) smear-positive prior contacts and 0/17 smear-negative prior contacts. Confirmed transmission was more common in those related to the prior contact (42.4%, 56/132) than in non-relatives (19.4%, 6/31, p = 0.02), and in those with more intense contact, to younger index cases, and in more recent years. The proportion of tuberculosis attributable to known contacts was estimated to be 9.4% overall. CONCLUSIONS: In this population known contacts only explained a small proportion of tuberculosis cases. Even those with a prior family contact with smear positive tuberculosis were more likely to have acquired their infection elsewhere

The impact of HIV and ART on recurrent tuberculosis in a sub-Saharan setting.

OBJECTIVE: To estimate the impact of antiretroviral therapy (ART) on the incidence of recurrent tuberculosis (TB) in an African population. DESIGN: A long-term population cohort in Karonga District, northern Malawi. METHODS: Patients who had completed treatment for laboratory-confirmed TB diagnosed since 1996 were visited annually to record vital status, ART use and screen for TB. Survival analysis estimated the effect of HIV/ART status at completion of treatment on mortality and recurrence. Analyses were stratified by time since treatment completion to estimate the effects on relapse (predominates during first year) and reinfection disease (predominates later). RESULTS: Among 1133 index TB cases contributing 4353 person-years of follow-up, there were 307 deaths and 103 laboratory-confirmed recurrences (recurrence rate 4.6 per 100 person-years). Half the recurrences occurred in the first year since completing treatment. HIV infection increased the recurrence rate [rate ratio adjusted for age, sex, period and TB type 2.69, 95% confidence interval (CI) 1.69-4.26], but with less effect in the first year (adjusted rate ratio 1.71, 95% CI 0.87-3.35) than subsequently (adjusted rate ratio 4.2, 95% CI 2.16-8.15). Recurrence rates on ART were intermediate between those of HIV-negative individuals and HIV-positive individuals without ART. Compared with HIV-positive individuals without ART, the adjusted rate ratio was 0.74 (95% CI 0.27-2.06) in the first year, and 0.43 (95% CI 0.11-1.73) later. CONCLUSION: The increased incidence of TB recurrence observed in HIV-positive patients appeared to be reduced by ART. The effects are mostly on later (likely reinfection) disease so the impact of ART on reducing recurrence will be highest in high TB incidence settings

HIV and the risk of tuberculosis due to recent transmission over 12 years in Karonga District, Malawi☆

Tuberculosis (TB) patients with strains common to other recent cases (‘clustering’) suggest recent transmission. HIV status and age may affect proportions clustered. We investigated TB clustering by HIV and age in a population-based study in Malawi. Among 746 patients, HIV infection increased the proportion clustered. Sex-period-adjusted odds ratios for the association of HIV and clustering were 1.26 (95% CI 0.4–4.1) for ages 15–25 years, 1.40 (0.9–2.3) for 25–50 years and 10.44 (2.3–47.9) for >50 years and remained stable over two periods examined. These results suggest that HIV increases the proportion of TB due to recent transmission in the elderly

Flow-chart of patients included in the study.

<p>Flow-chart of patients included in the study.</p

Estimate of the proportion of first episode culture-confirmed cases attributable to known smear positive contacts.

<p>*The proportion with other contacts excludes those with family contacts as well</p><p>PAF = population attributable fraction.</p><p>Estimate of the proportion of first episode culture-confirmed cases attributable to known smear positive contacts.</p

Number of confirmed transmissions by characteristics of the prior contact, the case, and the relationship between them among 163 case-prior contact pairs in which the prior contact had smear positive pulmonary tuberculosis.

<p>* from Χ² tests or Fisher’s exact tests if numbers are small.</p><p>Number of confirmed transmissions by characteristics of the prior contact, the case, and the relationship between them among 163 case-prior contact pairs in which the prior contact had smear positive pulmonary tuberculosis.</p

Number of SNPs between index patients and identified prior contacts, by sputum smear status of the prior contact.

<p>Number of SNPs between index patients and identified prior contacts, by sputum smear status of the prior contact.</p

Number of SNPs by time interval between successive cases in 62 case-contact pairs with confirmed transmission.

<p>(Random noise has been introduced to allow those with identical numbers of SNPs to be visualised).</p