Factors affecting immunogenicity of BCG in infants, a study in Malawi, The Gambia and the UK.

BACKGROUND: BCG immunogenicity in infants differs between populations and these differences have been attributed to various factors. In this study, the influence of geographical location, season of birth, timing of vaccination, micronutrient status (zinc) and inflammatory status (C-reactive protein, CRP) were assessed. METHODS: Immunogenicity was assessed by cytokine signature in culture supernatants from diluted whole blood samples stimulated with M. tuberculosis PPD, using a multiplex bead assay. Results were correlated with the plasma zinc and CRP concentrations at the time of sampling, and with interview and household data. BCG vaccinated infants were recruited in Malawi, The Gambia and the UK. RESULTS: In Malawi, infants vaccinated within the first week after birth showed lower production of most cytokines measured than those vaccinated later. The number of cytokines showing significant differences between Malawian and Gambian infants decreased after adjusting for season of birth. In Malawi, a proportion of infants had zinc deficiency and elevated plasma CRP (>10 mg/L), but neither zinc deficiency nor high CRP was associated with production of any of the cytokines measured. CONCLUSIONS: The cytokine/chemokine signatures observed in response to M. tuberculosis PPD in infants at 3 months post BCG vaccination were affected by geographical location, season of birth, and timing of vaccination but not associated with the concentration of plasma zinc or inflammatory status. These factors should be considered in future trials of new TB vaccines.

Timing of antiretroviral therapy and regimen for HIV-infected patients with tuberculosis: the effect of revised HIV guidelines in Malawi.

BACKGROUND: In July 2011, the Malawi national HIV program implemented the integrated antiretroviral therapy (ART) and prevention of mother-to-child transmission (PMTCT) guidelines. Among the principle goals of the guidelines were increasing ART uptake among TB/HIV co-infected patients and treating TB/HIV patients with a different drug regimen. We, therefore, assessed the effects of the new guidelines on ART uptake, the factors associated with ART uptake and the frequency of ARV-related adverse events in TB/HIV co-infected patients. METHODS: This was an observational cohort study using routine program data. All ART-naïve adult TB/HIV co-infected patients starting TB treatment over the six months preceding and following implementation of 2011 integrated ART/PMTCT guidelines were included. RESULTS: A total of 685 adult TB/HIV co-infected patients were registered in the study; 377 (55%) before and 308 (45%) after the implementation of the new guidelines. ART uptake increased from 70% (240/308) before implementation of the new guidelines to 78% (262/377) after the inception of the new guidelines (P=0.013). The proportion of TB patients initiating ART within two weeks of starting TB treatment increased from 30% before implementation of the new guidelines to 46% after implementation of the new guidelines (p <0.001). The median time from the start of TB treatment to ART initiation dropped from 16 days (IQR 14-31) before the new guidelines to 14 days (IQR 9-20; p = 0.004) after implementing the new guidelines. Factors associated with ART uptake were enrolment in HIV care before starting TB treatment and being a retreatment TB patient. The overall frequency of ARV-related adverse events was higher in patients on d4T/3TC/NVP (35%) than those on TDF/3TC/EFV (25%) but not significantly different (P=0.052). CONCLUSION: Implementation of the 2011 Malawi Integrated ART/PMTCT guidelines was associated with an overall increase in ART uptake among TB/HIV patients and with an increase in the number of patients initiating ART within two weeks of starting their TB treatment. However, the reduction in time between initiating TB treatment and starting ART was small suggesting that further measures must be implemented to facilitate ART uptake. Early enrolment in HIV care provides opportunities for timely ART initiation among TB patients.

Incidence of pregnancy among women accessing antiretroviral therapy in urban Malawi: a retrospective cohort study.

Although previous studies investigated pregnancy rates among women on antiretroviral therapy (ART), incidence of, and factors associated with pregnancy among these women remain poorly understood. We, therefore, conducted a retrospective cohort study at a large public HIV clinic in Lilongwe, Malawi, between July 2007 and December 2010. At each clinic visit, pregnancy status was assessed. Time to event analysis was conducted using Poisson regression. Among 4,738 women, 589 pregnancies were observed. Pregnancy incidence was 9.3/100 person-years. After 6 months on ART, women on ART had similar total fertility rates to women in the urban population. In multivariable analysis, increasing age and advanced WHO clinical stage were associated with decreased probability of becoming pregnant while higher body mass index and longer time on ART were associated with increased probability of becoming pregnant. We recommend that ART clinics integrate comprehensive family planning services to address reproductive health needs among women on ART.

Simplifying ART cohort monitoring: can pharmacy stocks provide accurate estimates of patients retained on antiretroviral therapy in Malawi?

BACKGROUND: Routine monitoring of patients on antiretroviral therapy (ART) is crucial for measuring program success and accurate drug forecasting. However, compiling data from patient registers to measure retention in ART is labour-intensive. To address this challenge, we conducted a pilot study in Malawi to assess whether patient ART retention could be determined using pharmacy records as compared to estimates of retention based on standardized paper- or electronic based cohort reports. METHODS: Twelve ART facilities were included in the study: six used paper-based registers and six used electronic data systems. One ART facility implemented an electronic data system in quarter three and was included as a paper-based system facility in quarter two only. Routine patient retention cohort reports, paper or electronic, were collected from facilities for both quarter two [April-June] and quarter three [July-September], 2010. Pharmacy stock data were also collected from the 12 ART facilities over the same period. Numbers of ART continuation bottles recorded on pharmacy stock cards at the beginning and end of each quarter were documented. These pharmacy data were used to calculate the total bottles dispensed to patients in each quarter with intent to estimate the number of patients retained on ART. Information for time required to determine ART retention was gathered through interviews with clinicians tasked with compiling the data. RESULTS: Among ART clinics with paper-based systems, three of six facilities in quarter two and four of five facilities in quarter three had similar numbers of patients retained on ART comparing cohort reports to pharmacy stock records. In ART clinics with electronic systems, five of six facilities in quarter two and five of seven facilities in quarter three had similar numbers of patients retained on ART when comparing retention numbers from electronically generated cohort reports to pharmacy stock records. Among paper-based facilities, an average of 13 4 hours was needed to calculate patient retention for cohort reporting using patient registers as compared to 2.25 hours using pharmacy stock cards. CONCLUSION: The numbers of patients retained on ART as estimated using pharmacy stock records were largely similar to estimates based on either paper registers or electronic data system. Furthermore, less time and staff effort was needed to estimate ART patient retention using pharmacy stock records versus paper-based registers. Reinforcing ARV stock management may improve the precision of estimates.

BCG vaccination induces different cytokine profiles following infant BCG vaccination in the UK and Malawi.

BACKGROUND: BCG vaccination of infants is thought to provide good protection in all settings. This study investigated whether Malawian infants made weaker responses across a cytokine panel after BCG vaccination, compared with UK infants. METHODS: Diluted whole-blood samples were cultured with Mycobacterium tuberculosis purified protein derivative for 6 days from BCG-vaccinated infants 3 months (n = 40 Malawi, 28 UK) and 12 months (n = 34 Malawi, 26 UK) after vaccination, and also from UK unvaccinated infants (n = 9 at 3 months, n = 10 at 12 months). Forty-two cytokines were measured in supernatants using a multiplex bead array assay. Principal component analysis was used to summarize the overall patterns in cytokine responses. RESULTS: We found differences in median responses in 27 of the 42 cytokines: 7 higher in the UK and 20 higher in Malawi. The cytokines with higher responses in the UK were all T helper 1 related. The cytokines with higher responses in Malawi included innate proinflammatory cytokines, regulatory cytokines, interleukin 17, T helper 2 cytokines, chemokines, and growth factors. Principal component analysis separated the BCG-vaccinated infants from Malawi from the UK vaccinated infants and from the unvaccinated infants. CONCLUSIONS: Malawian infants make cytokine responses following BCG vaccination, but the cytokine profile is different from that in the UK. The different biosignatures following BCG vaccination in the 2 settings may indicate variability in the protective efficacy of infant BCG vaccination.

Early active follow-up of patients on antiretroviral therapy (ART) who are lost to follow-up: the 'Back-to-Care' project in Lilongwe, Malawi.

OBJECTIVES: To determine the proportion of patients returning to antiretroviral treatment (ART) and factors associated with their return in a resource-limited setting. METHODS: Between September 2006 and March 2009, at two ART-providing facilities in Lilongwe, Malawi, we identified patients who had missed clinic appointments by more than 3 weeks and therefore would have run out of antiretroviral drugs. We traced these individuals, documented reasons for missed appointments and, where appropriate, arranged another ART clinic appointment. RESULTS: Between April 2006 and March 2009, 2653 patients on ART had missed 3098 scheduled appointments. We successfully traced 85%, of whom 30% had died. Of the 1580 patients found alive, 25% had transferred to another ART clinic, 21% had collected drugs from other sources, 11% had treatment gaps; 40% had stopped taking drugs, 1% had not started taking drugs despite collecting them and 2% refused to be interviewed. Of the 1158 LTFU patients who had not died, transferred out or declined to be interviewed, 89% promised to return to their ART clinic and 74% actually did. The probability of returning to the clinic was significantly associated with being women, aged over 39 at ART initiation and having either treatment gaps or uninterrupted therapy. The B2C project reduced the proportion of patients finally classified as LTFU by 59%. CONCLUSION: Early active follow-up of LTFU patients resulted in marked improvement in known patient outcomes and improved retention in the treatment programme.

Different delivery models for antiretroviral therapy in sub-Saharan Africa in the context of 'universal access'.

In 10 years, in line with the concept of universal access, 25 million HIV-infected patients in sub-Saharan Africa might be on antiretroviral therapy (ART). There are different models of ART delivery, from the individualised, medical approach to the simple, public health approach, both having distinct advantages and disadvantages. This mini-review highlights the essential components of both models and argues that, whatever the mix of different models in a country, both must be underpinned by similar core principles so that uninterrupted drug supplies, patient adherence to therapy and compliance with follow up are assured. Failure to do otherwise is to court disaster.

Persistence of the immune response induced by BCG vaccination.

BACKGROUND: Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. METHODS: A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-gamma) response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD) in a whole blood assay before, 3 months, 12 months (n = 148) and 3 years (n = 19) after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16). RESULTS: A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13%) failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13%) or 3 (3/19; 16%) years. IFN-gamma response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81%) made a detectable IFN-gamma response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38%) matched unvaccinated controls (p = 0.012); teenagers vaccinated in infancy were 19 times more likely to make an IFN-gamma response of > 500 pg/ml than unvaccinated teenagers. CONCLUSION: BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the majority of vaccinees, although the magnitude of the peripheral blood response wanes from 3 months to 12 months and from 12 months to 3 years post vaccination. The data presented here suggest that because of such waning in the response there may be scope for boosting anti-tuberculous immunity in BCG vaccinated children anytime from 3 months post-vaccination. This supports the prime boost strategies being employed for some new TB vaccines currently under development.

Differences between naive and memory T cell phenotype in Malawian and UK adolescents: a role for Cytomegalovirus?

BACKGROUND: Differences in degree of environmental exposure to antigens in early life have been hypothesized to lead to differences in immune status in individuals from different populations, which may have implications for immune responses in later years. METHODS: Venous blood from HIV-negative adolescents and blood from the umbilical cords of babies, born to HIV-negative women, post-delivery was collected and analysed using flow cytometry. T cell phenotype was determined from peripheral blood lymphocytes and cytomegalovirus (CMV) seropositivity was assessed by ELISA in adolescents. RESULTS: HIV-negative Malawian adolescents were shown to have a lower percentage of naïve T cells (CD45RO-CD62Lhi CD11alo), a higher proportion of memory T cells and a higher percentage of CD28- memory (CD28-CD45RO+) T cells compared to age-matched UK adolescents. Malawian adolescents also had a lower percentage of central memory (CD45RA-CCR7+) T cells and a higher percentage of stable memory (CD45RA+CCR7-) T cells than UK adolescents. All of the adolescents tested in Malawi were seropositive for CMV (59/59), compared to 21/58 (36%) of UK adolescents. CMV seropositivity in the UK was associated with a reduced percentage of naïve T cells and an increased percentage of CD28- memory T cells in the periphery. No differences in the proportions of naïve and memory T cell populations were observed in cord blood samples from the two sites. CONCLUSION: It is likely that these differences between Malawian and UK adolescents reflect a greater natural exposure to various infections, including CMV, in the African environment and may imply differences in the ability of these populations to induce and maintain immunological memory to vaccines and natural infections.

Informatics solutions for bridging the gap between clinical and laboratory services in a low-resource setting.

Background: There has been little formal analysis of laboratory systems in resource-limited settings, despite widespread consensus around the importance of a strong laboratory infrastructure. Objectives: This study details the informational challenges faced by the laboratory at Kamuzu Central Hospital, a tertiary health facility in Malawi; and proposes ways in which informatics can bolster the efficiency and role of low-resource laboratory systems. Methods: We evaluated previously-collected data on three different aspects of laboratory use. A four-week quality audit of laboratory test orders quantified challenges associated with collecting viable specimens for testing. Data on tests run by the laboratory over a one-year period described the magnitude of the demand for laboratory services. Descriptive information about the laboratory workflow identified informational process breakdowns in the pre-analytical and post-analytical phases and was paired with a 24-hour sample of laboratory data on results reporting. Results: The laboratory conducted 242 242 tests over a 12-month period. The four-week quality audit identified 54% of samples as untestable. Prohibitive paperwork errors were identified in 16% of samples. Laboratory service workflows indicated a potential process breakdown in sample transport and results reporting resulting from the lack of assignment of these tasks to any specific employee cadre. The study of result reporting time showed a mean of almost six hours, with significant variation. Conclusions: This analysis identified challenges in each phase of laboratory testing. Informatics could improve the management of this information by streamlining test ordering and the communication of test orders to the laboratory and results back to the ordering physician.

gamma delta T cells infiltrating sensory nerve biopsies from patients with inflammatory neuropathy.

Sensory nerve biopsy specimens from patients with Guillain Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and controls consisting of other neuropathies, were examined in order to characterise the nature and intensity of any inflammatory infiltrate. In order to establish whether gamma delta T cells were present in these infiltrates we examined the expression of alpha beta and gamma delta T cell receptors in the biopsy specimens from patients with inflammatory neuropathy. A section of each biopsy specimen was simultaneously cultured in order to attempt to establish T cell lines. T cell lines were established in 4 out of 7 patients with GBS of which 2 were gamma delta in phenotype. There was a significant correlation between the number of mononuclear cells detected by immunostaining within the biopsy specimens and the chance of successfully establishing a T cell line. Histological studies detected gamma delta T cell receptor in 2 out of the 7 patients with GBS, 14 out of the 20 with CIDP and in 5 out of the 13 controls (vasculitis 3, paraneoplastic 1, axonal neuropathy of uncertain cause 1). The presence of T cells of a gamma delta T cell receptor phenotype in nerve biopsy specimens from patients with inflammatory neuropathy is consistent with a possible pathogenetic role of a cellular immune response against non-protein antigens such as gangliosides.

Comparison of treatment outcomes of new smear-positive pulmonary tuberculosis patients by HIV and antiretroviral status in a TB/HIV clinic, Malawi.

BACKGROUND: Smear-positive pulmonary TB is the most infectious form of TB. Previous studies on the effect of HIV and antiretroviral therapy on TB treatment outcomes among these highly infectious patients demonstrated conflicting results, reducing understanding of important issues. METHODS: All adult smear-positive pulmonary TB patients diagnosed between 2008 and 2010 in Malawi's largest public, integrated TB/HIV clinic were included in the study to assess treatment outcomes by HIV and antiretroviral therapy status using logistic regression. RESULTS: Of 2,361 new smear-positive pulmonary TB patients, 86% had successful treatment outcome (were cured or completed treatment), 5% died, 6% were lost to follow-up, 1% failed treatment, and 2% transferred-out. Overall HIV prevalence was 56%. After adjusting for gender, age and TB registration year, treatment success was higher among HIV-negative than HIV-positive patients (adjusted odds ratio 1.49; 95% CI: 1.14-1.94). Of 1,275 HIV-infected pulmonary TB patients, 492 (38%) received antiretroviral therapy during the study. Pulmonary TB patients on antiretroviral therapy were more likely to have successful treatment outcomes than those not on ART (adjusted odds ratio : 1.83; 95% CI: 1.29-2.60). CONCLUSION: HIV co-infection was associated with poor TB treatment outcomes. Despite high HIV prevalence and the integrated TB/HIV setting, only a minority of patients started antiretroviral therapy. Intensified patient education and provider training on the benefits of antiretroviral therapy could increase antiretroviral therapy uptake and improve TB treatment success among these most infectious patients.

Are they really lost? "true" status and reasons for treatment discontinuation among HIV infected patients on antiretroviral therapy considered lost to follow up in Urban Malawi.

INTRODUCTION: Patients who are lost to follow-up (LTFU) while on antiretroviral therapy (ART) pose challenges to the long-term success of ART programs. We describe the extent to which patients considered LTFU are misclassified as true disengagement from care when they are still alive on ART and explain reasons for ART discontinuation using our active tracing program to further improve ART retention programs and policies. METHODS: We identified adult ART patients who missed clinic appointment by more than 3 weeks between January 2006 and December 2010, assuming that such patients would miss their doses of antiretroviral drugs. Patients considered LTFU who consented during ART registration were traced by phone or home visits; true ART status after tracing was documented. Reasons for ART discontinuation were also recorded for those who stopped ART. RESULTS: Of the 4,560 suspected LTFU cases, 1,384 (30%) could not be traced. Of the 3,176 successfully traced patients, 952 (30%) were dead and 2,224 (70%) were alive, of which 2,183 (99.5%) started ART according to phone-based self-reports or physical verification during in-person interviews. Of those who started ART, 957 (44%) stopped ART and 1,226 (56%) reported still taking ART at the time of interview by sourcing drugs from another clinic, using alternative ART sources or making brief ART interruptions. Among 940 cases with reasons for ART discontinuations, failure to remember (17%), too weak/sick (12%), travel (46%), and lack of transport to the clinic (16%) were frequently cited; reasons differed by gender. CONCLUSION: The LTFU category comprises sizeable proportions of patients still taking ART that may potentially bias retention estimates and misdirect resources at the clinic and national levels if not properly accounted for. Clinics should consider further decentralization efforts, increasing drug allocations for frequent travels, and improving communication on patient transfers between clinics to increase retention and adherence.

Combination of cytokine responses indicative of latent TB and active TB in Malawian adults.

BACKGROUND: An IFN-γ response to M. tuberculosis-specific antigens is an effective biomarker for M. tuberculosis infection but it cannot discriminate between latent TB infection and active TB disease. Combining a number of cytokine/chemokine responses to M. tuberculosis antigens may enable differentiation of latent TB from active disease. METHODS: Asymptomatic recently-exposed individuals (spouses of TB patients) were recruited and tuberculin skin tested, bled and followed-up for two years. Culture supernatants, from a six-day culture of diluted whole blood samples stimulated with M. tuberculosis-derived PPD or ESAT-6, were measured for IFN-γ, IL-10, IL-13, IL-17, TNF-α and CXCL10 using cytokine ELISAs. In addition, 15 patients with sputum smear-positive pulmonary TB were recruited and tested. RESULTS: Spouses with positive IFN-γ responses to M. tuberculosis ESAT-6 (>62.5 pg/mL) and TB patients showed high production of IL-17, CXCL10 and TNF-α. Higher production of IL-10 and IL-17 in response to ESAT-6 was observed in the spouses compared with TB patients while the ratios of IFN-γ/IL-10 and IFN-γ/IL-17 in response to M. tuberculosis-derived PPD were significantly higher in TB patients compared with the spouses. Tuberculin skin test results did not correlate with cytokine responses. CONCLUSIONS: CXCL10 and TNF-α may be used as adjunct markers alongside an IFN-γ release assay to diagnose M. tuberculosis infection, and IL-17 and IL-10 production may differentiate individuals with LTBI from active TB.

Schistosoma co-infection protects against brain pathology but does not prevent severe disease and death in a murine model of cerebral malaria.

Co-infections of helminths and malaria parasites are common in human populations in most endemic areas. It has been suggested that concomitant helminth infections inhibit the control of malaria parasitemia but down-modulate severe malarial disease. We tested this hypothesis using a murine co-infection model of schistosomiasis and cerebral malaria. C57BL/6 mice were infected with Schistosoma mansoni and 8-9 weeks later, when Schistosoma infection was patent, mice were co-infected with Plasmodium berghei ANKA strain. We found that a concomitant Schistosoma infection increased parasitemia at the beginning of the P. berghei infection. It did not protect against P. berghei-induced weight loss and hypothermia, and P. berghei-mono-infected as well as S. mansoni-P. berghei-co-infected animals showed a high case fatality between days 6 and 8 of malarial infection. However, co-infection significantly reduced P. berghei-induced brain pathology. Over 40% of the S. mansoni-P. berghei-co-infected animals that died during this period were completely protected against haemorrhaging, plugging of blood vessels and infiltration, indicating that mortality in these animals was not related to cerebral disease. Schistosoma mansoni-P. berghei-co-infected mice had elevated plasma concentrations of IL-5 and IL-13 and on day 6 lower levels of IFN-γ, IL-10, monocyte chemoattractant protein-1 (MCP-1) and monokine induced by IFN-γ (MIG) than P. berghei-mono-infected mice. We conclude that in P. berghei infections, disease and early death are caused by distinct pathogenic mechanisms, which develop in parallel and are differentially influenced by the immune response to S. mansoni. This might explain why, in co-infected mice, death could be induced in the absence of brain pathology.

Antiretroviral drug supply challenges in the era of scaling up ART in Malawi.

The number of people receiving antiretroviral treatment (ART) has increased considerably in recent years and is expected to continue to grow in the coming years. A major challenge is to maintain uninterrupted supplies of antiretroviral (ARV) drugs and prevent stock outs. This article discusses issues around the management of ARVs and prevention of stock outs in Malawi, a low-income country with a high HIV/AIDS burden, and a weak procurement and supply chain management system. This system for ARVs, paid for by the Global Fund to Fight AIDS, Tuberculosis and Malaria, and bypassing the government Central Medical Stores, is in place, using the United Nations Children's Fund's (UNICEF's) procurement services. The system, managed by a handful of people who spend limited time on supply management, is characterized by a centrally coordinated quantification based on verified data from all national ART clinics, parallel procurement through UNICEF, and direct distribution to ART clinics. The model worked well in the first years of the ART programme with a single first-line ARV regimen, but with more regimens becoming available (e.g., alternative first-line, second-line and paediatric regimens), it has become more difficult to administer. Managing supplies through a parallel system has the advantage that weaknesses in the national system have limited influence on the ARV procurement and supply chain management system. However, as the current system operates without a central warehouse and national buffer stock capacity, it diminishes the ability to prevent ARV stock outs. The process of ordering ARVs, from the time that estimates are made to the arrival of supplies in health facilities, takes approximately one year. Addressing the challenges involved in maintaining ARVs through an efficient procurement and supply chain management system that prevents ARV stock outs through the establishment of a dedicated procurement team, a central warehouse and/or national buffer stock is a priority.

Re-treatment tuberculosis cases categorised as "other": are they properly managed?

BACKGROUND: Although the World Health Organization (WHO) provides information on the number of TB patients categorised as "other", there is limited information on treatment regimens or treatment outcomes for "other". Such information is important, as inappropriate treatment can lead to patients remaining infectious and becoming a potential source of drug resistance. Therefore, using a cohort of TB patients from a large registration centre in Lilongwe, Malawi, our study determined the proportion of all TB re-treatment patients who were registered as "other", and described their characteristics and treatment outcomes. METHODS: This retrospective observational study used routine program data to determine the proportion of all TB re-treatment patients who were registered as "other" and describe their characteristics and treatment outcomes between January 2006 and December 2008. RESULTS: 1,384 (12%) of 11,663 TB cases were registered as re-treatment cases. Of these, 898 (65%) were categorised as "other": 707 (79%) had sputum smear-negative pulmonary TB and 191 (21%) had extra pulmonary TB. Compared to the smear-positive relapse, re-treatment after default (RAD) and failure cases, smear-negative "other" cases were older than 34 years and less likely to have their HIV status ascertained. Among those with known HIV status, "other" TB cases were more likely to be HIV positive. Of TB patients categorised as "other", 462 (51%) were managed on the first-line regimen with a treatment success rate of 63%. CONCLUSION: A large proportion of re-treatment patients were categorised as "other". Many of these patients were HIV-infected and over half were treated with a first-line regimen, contrary to national guidelines. Treatment success was low. More attention to recording, diagnosis and management of these patients is warranted as incorrect treatment regimen and poor outcomes could lead to the development of drug resistant forms of TB.