Decline in adverse outcomes and death in tuberculosis patients in Malawi: association with HIV interventions

Between 2000 and 2012, the annual numbers of patients treated for tuberculosis (TB) in Malawi declined by 28%, from 28 234 to 20 463. During this time, the proportion of TB patients tested for the human immunodeficiency virus (HIV) increased from 6% to 87%. Most HIV-infected patients received cotrimoxazole preventive therapy, and the proportion receiving antiretroviral therapy increased to 88%. Between 2000 and 2008 there was a significant decline in all adverse outcomes (from 31% to 14%), and particularly in deaths (from 23% to 10%) and loss to follow-up (from 5.2% to 1.9%, P < 0.001). After 2008, there was no decrease in any adverse outcome. Ways to further reduce TB-associated mortality are discussed.     

Decline in national tuberculosis notifications with national scale-up of antiretroviral therapy in Malawi

From 2000 to 2012, Malawi scaled up antiretroviral therapy (ART) from <3000 to 404 905 persons living with HIV/AIDS (human immunodeficiency virus/acquired immune-deficiency syndrome), representing an ART coverage of 40.6% among those living with HIV. During this time, annual tuberculosis (TB) notifications declined by 28%, from 28 234 to 20 463. Percentage declines in annual TB case notifications were as follows: new TB (26%), recurrent TB (40%), new smear-positive pulmonary TB (19%), new smear-negative pulmonary TB (42%), extra-pulmonary TB (19%), HIV-positive TB (30%) and HIV-negative TB (10%). The decline in TB notifications is associated with ART scale-up, supporting its value in controlling TB in high HIV prevalence areas in sub-Saharan Africa.     

Timing and uptake of ART during treatment for active tuberculosis in HIV co-infected adults in Malawi

Setting:

Uptake of antiretroviral therapy (ART) in patients co-infected with tuberculosis (TB) and the human immunodeficiency virus (HIV) has historically been low in Malawi. In response, the National TB Programme piloted the initiation of ART 2 weeks after initiation of TB treatment in 2008–2009, a change from the prior policy of 2 months.

Objective:

To determine at programme level if earlier initiation of ART in co-infected patients receiving TB treatment will increase the uptake and continuation of ART.

Design:

A prospective observational pilot programme evaluation using routinely collected monitoring data from the first two sites with integrated TB-HIV services in Malawi.

Results:

There was wide variability in the ART start time before and after the policy change. Before the policy change, 16% of patients initiated ART by 3 months compared to 24% after the policy change (P < 0.001). The proportion of all co-infected patients on ART increased from 32% before the policy change to 39% after (P < 0.001). Earlier initiation of ART did not increase the occurrence of side effects and did not reduce adherence to TB treatment.

Conclusion:

Earlier initiation of ART in co-infected patients receiving TB treatment improved the uptake and continuation of ART. Malawi ART guidelines in 2011 were changed from initiating ART after 2 months to as soon as possible after starting anti-tuberculosis treatment.     

Community support is associated with better antiretroviral treatment outcomes in a resource-limited rural district in Malawi

A study was carried in a rural district in Malawi among HIV-positive individuals placed on antiretroviral treatment (ART) in order to verify if community support influences ART outcomes. Standardized ART outcomes in areas of the district with and without community support were compared. Between April 2003 (when ART was started) and December 2004 a total of 1634 individuals had been placed on ART. Eight hundred and ninety-five (55%) individuals were offered community support, while 739 received no such support. For all patients placed on ART with and without community support, those who were alive and continuing ART were 96 and 76%, respectively (P<0.001); death was 3.5 and 15.5% (P<0.001); loss to follow-up was 0.1 and 5.2% (P<0.001); and stopped ART was 0.8 and 3.3% (P<0.001). The relative risks (with 95% CI) for alive and on ART [1.26 (1.21-1.32)], death [0.22 (0.15-0.33)], loss to follow-up [0.02 (0-0.12)] and stopped ART [0.23 (0.08-0.54)] were all significantly better in those offered community support (P<0.001). Community support is associated with a considerably lower death rate and better overall ART outcomes. The community might be an unrecognized and largely 'unexploited resource' that could play an important contributory role in countries desperately trying to scale up ART with limited resources.     

Characteristics and outcomes of tuberculosis patients who fail to smear convert at two months in Sri Lanka

Setting:

Five districts in Sri Lanka.

Objectives:

To determine: 1) the proportion of sputum smear-positive pulmonary tuberculosis (PTB) cases who failed to smear convert at 2 months, 2) their management, and 3) whether baseline characteristics and final treatment outcomes were different from those who did smear convert.

Design:

Cross-sectional retrospective review of medical files, tuberculosis (TB) registers and TB treatment records of new smear-positive PTB patients registered from January to December 2010.

Results:

Of 925 patients, 840 were available to submit sputum at 2 months, of whom 137 (16%) were smear-positive. Baseline sputum smears showing 3+ acid-fast bacilli and missing doses of anti-tuberculosis drugs during the initial phase of treatment were significantly associated with being smear-positive at 2 months. Management was poor: of 137 patients, 46 (34%) submitted sputum for culture and drug susceptibility testing and Mycobacterium tuberculosis was cultured in six cases; 120 (88%) received a 1-month extension of the initial phase, and of the 30 patients still smear-positive at 3 months there were no culture results available. Final treatment outcomes were similar, regardless of smear conversion at 2 or 3 months.

Conclusion:

Certain characteristics were risk factors for failure to smear convert at 2 months. However, treatment outcomes for all patients were good. These findings have implications for the modification of national programme recommendations.     

Monitoring the response to antiretroviral therapy in resource-poor settings: the Malawi model

With assistance from the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM), Malawi is scaling-up the delivery of antiretroviral (ARV) therapy to HIV-positive eligible patients. The country has developed National ARV Treatment Guidelines, which emphasize a structured and standardized approach for all aspects of ARV delivery, including monitoring and evaluation. Using the successful DOTS model adapted by National TB Control Programmes throughout the world, Malawi has developed a system of quarterly ARV cohort and cumulative ARV quarterly analyses. Thyolo district, in the southern region of Malawi, has been using this system since April 2003. This paper describes the standardized ARV treatment regimens and the treatment outcomes used in Thyolo to assess the impact of treatment, the registration and monitoring systems and how the cohort analyses are carried out. Data are presented for case registration and treatment outcome for the first quarterly cohort (April to June) and the combined cohorts (April to June and July to September). Such quarterly analyses may be useful for districts and Ministries of Health in assessing ARV delivery, although the burden of work involved in calculating the numbers may become large once ARV delivery systems have been established for several years.     

Effect of universal MODS access on pulmonary tuberculosis treatment outcomes in new patients in Peru

Setting:

Primary health care centres in Callao, Peru.

Objectives:

To evaluate the effect of universal access to the microscopic-observation drug susceptibility (MODS) assay on treatment outcomes in new and primary multidrug-resistant tuberculosis (MDR-TB) patients and on the process of drug susceptibility testing (DST).

Design:

Retrospective review of tuberculosis (TB) registers and clinical records before (2007) and after (2009) the introduction of MODS in 2008.

Results:

There were 281 patients in each cohort. Favourable treatment outcomes for 2007 (81%) and 2009 (77%) cohorts were similar. There was an increase in loss to follow-up (from 6% to 10%, P = 0.04) and a reduction in failure rates (from 4% to 0.4%, P = 0.01) in the 2009 compared with the 2007 cohort. In new MDR-TB cases (n = 22), a favourable treatment outcome was improved (from 46% to 82%, P = 0.183) in the 2009 cohort. DST coverage improved (from 24% to 74%, P < 0.001), and a significant reduction in time to diagnosis of drug-susceptible (from 118 to 33 days, P < 0.001) and MDR-TB (from 158 to 52 days, P = 0.003) was observed in the 2009 cohort.

Conclusion:

Universal access to MODS increased DST coverage, reduced the time required to obtain DST results and was associated with reduced failure rates. MODS can make an important contribution to TB management and control in Peru.     

Collaborative activities and treatment outcomes in patients with HIV-associated tuberculosis in Viet Nam

Setting: The National Tuberculosis (TB) Programme in Viet Nam and Ho Chi Minh City (HCMC).Objectives: To determine 1) at national level between 2011 and 2013, the relationship between human immunodeficiency virus (HIV) testing, uptake of TB-HIV interventions and adverse treatment outcomes among TB-HIV patients; and 2) in HCMC in 2013, patient characteristics associated with adverse outcomes.Design: An ecological study reviewing aggregate nationwide data and a retrospective cohort review in HCMC.Results: Nationwide, from 2011 to 2013, HIV testing increased in TB patients from 58% to 68% and antiretroviral therapy (ART) increased in TB-HIV patients from 54% to 63%. Adverse treatment outcomes in TB-HIV patients increased from 24% to 27%, largely due to transfer out (5–9% increase) and death. The Northern and Highland regions showed poor uptake of TB-HIV interventions. In HCMC, 303 (27%) of 1110 TB-HIV patients had adverse outcomes, with higher risks observed in those with previously treated TB, those diagnosed as HIV-positive before TB onset and those never placed on cotrimoxazole or ART.Conclusion: Despite improving HIV testing rates and TB-HIV interventions, adverse outcomes in TB-HIV patients remain at about 26%. Characteristics predicting higher risk of adverse outcomes must be addressed if Viet Nam wishes to end the TB epidemic by 2030.     

Diagnostic management and outcomes of pulmonary tuberculosis suspects admitted to a central hospital in Malawi

Setting:

Zomba Central Hospital, Malawi.

Objective:

To determine diagnostic management and outcomes of pulmonary tuberculosis (PTB) suspects admitted to adult wards.

Design:

A retrospective, cross-sectional review of medical records of patients admitted to hospital between July and September 2010.

Results:

There were 141 PTB suspects. Sputum examination was requested and performed in 67 (48%) suspects, but none were smear-positive. Chest X-ray (CXR) was requested and performed in 26 (39%) suspects whose sputum smears were negative. Eleven suspects had a CXR suggestive of PTB: two were started on TB treatment and eight died before treatment started. Human immunodeficiency virus (HIV) status was known for 50 patients (35% of all suspects) on admission, all of whom were HIV-positive. HIV testing was requested for 37 patients, but was only performed in 12, five of whom were HIV-positive. Only one patient was referred for antiretroviral treatment. There were 41 (29%) deaths, eight of whom had probable TB and were not treated. In the remaining 33 patients who died, only nine (27%) had sputum smears examined and four (12%) had a CXR.

Conclusion:

The study shows inadequacies in the diagnostic management of PTB suspects in the Zomba Central Hospital, but suggests opportunities for improvement.     

Sputum smear examination and time to diagnosis in patients with smear-negative pulmonary tuberculosis in the Pacific

Setting:

National tuberculosis programmes (NTPs) in Kiribati and the Marshall Islands, 2006–2010.

Objective:

To determine the proportion of all tuberculosis (TB) cases that were pulmonary smear-negative, and for these patients to determine how many sputum smears were examined and the time from sputum smear examination to registration.

Design:

A retrospective cross-sectional study involving a record review of national TB and laboratory registers.

Results:

Of 2420 TB cases identified, 709 (29%) were registered as smear-negative pulmonary TB. Of the 695 (98%) with information on smear examination, 222 (32%) had no smear recorded, 61 (9%) had one smear, 86 (12%) two smears and 326 (47%) three smears. Among the 473 patients who had at least one smear, 238 (50%) were registered before sputum examination, 131 (28%) within 1 week, 72 (15%) between 1 and 4 weeks, and 34 (7%) >4 weeks after sputum examination.

Conclusion:

NTPs in Kiribati and the Marshall Islands are diagnosing 29% of all TB patients as smear-negative pulmonary TB. Many patients do not have smears done or are registered before undergoing smear examination. Corrective measures are needed.     

Screening tuberculosis patients for diabetes mellitus in Fiji: notes from the field

Diabetes (DM) is a problem in Fiji and threatens tuberculosis (TB) control efforts. A review was conducted of all TB patients registered in Fiji in 2011 to assess routine practices of screening for DM. Of 221 TB patients, 138 (62%) had their DM status recorded in their case folders; 18 (13%) had a known history of DM. Random blood glucose (RBG) was performed in 91 (76%) of the remaining 120 patients: 47(52%) had RBG ≥ 6.1 mmol/l, but only three were further investigated, of whom one was diagnosed with DM. There are deficiencies in screening TB patients for DM in Fiji, and improvements are needed.     

Characteristics and treatment outcomes of tuberculosis retreatment cases in three regional hospitals,Uganda

Setting:

Three regional referral hospitals in Uganda with a high burden of tuberculosis (TB) and human immunodeficiency virus (HIV) cases.

Objective:

To determine the treatment outcomes of TB retreatment cases and factors influencing these outcomes.

Design:

A retrospective cohort study of routinely collected National Tuberculosis Programme data between 1 January 2009 and 31 December 2010.

Results:

The study included 331 retreatment patients (68% males), with a median age of 36 years, 93 (28%) of whom were relapse smear-positive, 21 (6%) treatment after failure, 159 (48%) return after loss to follow-up, 26 (8%) relapse smear-negative and 32 (10%) relapse cases with no smear performed. Treatment success rates for all categories of retreatment cases ranged between 28% and 54%. Relapse smear-positive (P = 0.002) and treatment after failure (P = 0.038) cases were less likely to have a successful treatment outcome. Only 32% of the retreatment cases received a Category II treatment regimen; there was no difference in treatment success among patients who received Category II or Category I treatment regimens (P = 0.73).

Conclusion:

Management of TB retreatment cases and treatment success for all categories in three referral hospitals in Uganda was poor. Relapse smear-positive or treatment after failure cases were less likely to have a successful treatment outcome.     

Low prevalence of diabetes mellitus in patients with tuberculosis in Cotonou,Benin

Setting: The three Basic Management Units (BMUs) of the National Tuberculosis Programme (NTP) in Cotonou, Benin.Objective: To determine the prevalence of diabetes mellitus (DM) among tuberculosis (TB) patients in Cotonou.Design: A cross-sectional study of consecutively registered TB patients treated for a minimum of 2 weeks between June and July 2014 in the three BMUs, with measurement of their fasting blood glucose (FBG). A patient was considered as having DM if venous FBG was ⩾7 mmol/l or if they reported a known history of DM.Result: There were 159 patients assessed: 114 with new smear-positive pulmonary tuberculosis (PTB), 5 with new smear-negative PTB, 8 with extra-pulmonary TB, 21 retreatment patients with fully susceptible bacilli and 11 with multidrug-resistant TB. Of these, respectively 31 (19%), 18 (11%) and 10 (6%) were human immunodeficiency virus co-infected, smokers and hypertensive. Eight patients (5%) had impaired fasting glucose and three (1.9%) had DM (FBG ⩾ 7 mmol/l), of whom two were already known to have the disease and one was newly diagnosed.Conclusion: DM may not be an important risk factor for TB in Cotonou. A larger study on TB and DM in the whole country is needed.     

Management and treatment outcomes of patients enrolled in MDR-TB treatment in Viet Nam

Setting: The programmatic management of drug-resistant tuberculosis (TB) in Viet Nam has been rapidly scaled up since 2009.Objectives: To document the annual numbers of patients enrolled for multidrug-resistant tuberculosis (MDR-TB) treatment during 2010–2014 and to determine characteristics and treatment outcomes of patients initiating treatment during 2010–2012.Design: A retrospective cohort study using national reports and data from the national electronic data system for drug-resistant TB.Results: The number of patients enrolled annually for MDR-TB treatment increased from 97 in 2010 to 1522 in 2014. The majority of patients were middle-aged men who had pulmonary disease and had failed a retreatment regimen; 77% had received ⩾2 courses of TB treatment. Favourable outcomes (cured and treatment completed) were attained in 73% of patients. Unfavourable outcomes included loss to follow-up (12.5%), death (8%) and failure (6.3%). Having had ⩾2 previous treatment courses and being human immunodeficiency virus-positive were associated with unfavourable outcomes.Conclusion: Increasing numbers of patients are being treated for MDR-TB each year with good treatment outcomes under national programme management in Viet Nam. However, there is a need to increase case detection—currently at 30% of the estimated 5100 MDR-TB cases per year, reduce adverse outcomes and improve monitoring and evaluation.     

True outcomes for patients on antiretroviral therapy who are "lost to follow-up" in Malawi

PROBLEM: In many resource-poor countries that are scaling up antiretroviral therapy (ART), 5-25% of patients are reported as "lost to follow-up". This figure is 9% in Malawi. There is no published information about the true outcome status of these patients. APPROACH: In four facilities in northern Malawi, ART registers and master cards were used to identify patients who had not attended the facility for 3 months or more and were thus registered as "lost to follow-up". Clinic staff attempted to trace these patients and ascertain their true outcome status. LOCAL SETTING: Of 253 patients identified as "lost to follow-up", 127 (50%) were dead, 58% of these having died within 3 months of their last clinic visit. Of the 58 patients (23%) found to be alive, 21 were still receiving ART and 37 had stopped treatment (high transport costs being the main reason for 13 patients). Sixty-eight patients (27%) could not be traced, most commonly because of an incorrect address in the register. Fewer patients were alive and more patients could not be traced from the central hospital compared with the peripheral hospitals. RELEVANT CHANGES:Better documentation of patients addresses and prompt follow-up of patients who are late for their appointments are required. LESSONS LEARNED: ART clinics in resource-poor countries should ensure that patients addresses are correct and comprehensive. Clinics should also undertake contact tracing as soon as possible in the event of non-attendance, consider facilitating access to ART clinics and take loss to follow-up into consideration when assessing death rates.     

Tuberculosis treatment outcomes among retreatment patients registered by private practitioners in Myanmar

The objectives of this retrospective cohort study were to report treatment outcomes and identify factors associated with treatment failure among all retreatment tuberculosis (TB) patients registered in the public-private mix DOTS programme of Populations Services International–Myanmar over 6 years. Among 3643 retreatment patients, 2657 (73%) were successfully treated and 309 (8.5%) failed. This study shows that retreatment patients who have failed treatment for their first TB episode are almost twice as likely to fail a second time (13.5%). We have identified some key programmatic challenges associated with retreatment TB in the private sector, and steps are being taken to address this issue.     

Antiretroviral therapy during tuberculosis treatment and marked reduction in death rate of HIV-infected patients, Thailand

Antiretroviral therapy (ART) is lifesaving in patients with advanced HIV infection, but the magnitude of benefit in HIV-infected patients receiving tuberculosis (TB) treatment remains uncertain, and population-based data from developing countries are limited. We prospectively collected data about HIV-infected TB patients from February 2003 through January 2004 in Ubon-ratchathani, Thailand. During 12 months, HIV was diagnosed in 329 (14%) of 2,342 patients registered for TB treatment. Of patients with known outcomes, death during TB treatment occurred in 5 (7%) of 71 who received ART and 94 (43%) of 219 who did not. Using multivariate analysis, we found a large reduction in the odds of death for patients receiving ART before or during TB treatment (odds ratio, 0.2; 95% confidence interval, 0.1-0.5), adjusting for CD4 count, smear status, co-trimoxazole use, and treatment facility. ART is associated with a substantial reduction in deaths during TB treatment for HIV-infected TB patients in Thailand.     

Targeting CD4 testing to a clinical subgroup of patients could limit unnecessary CD4 measurements, premature antiretroviral treatment and costs in Thyolo District, Malawi

Malawi offers antiretroviral treatment (ART) to all HIV-positive adults who are clinically classified as being in WHO clinical stage III or IV without 'universal' CD4 testing. This study was conducted among such adults attending a rural district hospital HIV/AIDS clinic (a) to determine the proportion who have CD4 counts >or=350 cells/microl, (b) to identify risk factors associated with such CD4 counts and (c) to assess the validity and predictive values of possible clinical markers for CD4 counts >or=350 cells/microl. A CD4 count >or=350 cells/microl was found in 36 (9%) of 401 individuals who are thus at risk of being placed prematurely on ART. A body mass index (BMI) >22 kg/m(2), the absence of an active WHO indicator disease at the time of presentation for ART, and a total lymphocyte count >1,200 cells/microl were significantly associated with such a CD4 count. The first two of these variables could serve as clinical markers for selecting subgroups of patients who should undergo CD4 testing. In a resource-limited district setting, assessing the BMI and checking for active opportunistic infections are routine clinical procedures that could be used to target CD4 measurements, thereby minimising unnecessary CD4 measurements, unnecessary (too early) treatment and costs.     

The social construction of AIDS during a time of evolving access to antiretroviral therapy in rural Malawi

This paper draws upon a set of conversational journals collected over the past decade in rural Malawi, to understand how perceptions of AIDS are constructed as talk of antiretroviral therapy (ART) filters through social networks. Three distinct treatment eras frame our analysis: the early ART era (2001–2003), the ART expansion era (2004–2006) and the later ART era (2007–2009). We find that the early ART era was characterised by widespread fatalism as people recalled experiences with dying family and friends from what was perceived as an incurable and deadly disease. During the ART expansion era, AIDS fatalism was gradually replaced with a sense of uncertainty as rural Malawians became faced with two opposing realities: death from AIDS and prolonged life after ART. In the later ART era, the journals chart the rise of more optimistic beliefs about AIDS as rural Malawians slowly became convinced of ART's therapeutic payoffs. We conclude with an example of how ART created difficulties for rural Malawians to socially diagnose the disease and determine who was a safe sexual partner.