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Recurrent tuberculosis among HIV-coinfected patients: a case series from KwaZulu-Natal.

ABSTRACT: Background:Recurrent tuberculosis (TB) following TB treatment completion in HIV-infected individuals remains a major public health burden. We assessed the role of various risk factors in mediating the development of recurrent TB and subsequent resistance to antiretroviral therapy and anti-TB drugs. Patients and methods:We analyzed secondary demographic, clinical, and laboratory data from medical records of five HIV-infected TB patients enrolled between 2009 and 2014 in a prospective observational study investigating TB recurrence. Paired clinical isolates of Myco-bacterium tuberculosis were typed by IS6110 restriction fragment length polymorphism analysis to determine the mechanism of TB recurrence. Plasma samples were genotyped to determine acquisition of HIV drug resistance mutations on antiretroviral treatment (ART). Results:All five patients were HIV-coinfected, with a previous history of TB infection and prior exposure to anti-TB treatment, and residual lung damage, and demonstrated poor treatment adherence - significant risk factors linked to the development of recurrent TB disease. Furthermore, three of the five patients had multiple episodes of drug-susceptible TB infection with subsequent drug-resistant TB infection. Genotyping of the initial and recurrent M. tuberculosis isolates demonstrated three cases of recurrent TB because of relapse and two because of reinfection. All five patients had no mutations at ART initiation; however, by the end of the study follow-up, all patients developed dual class resistance. Conclusion:This series demonstrates the complexity of recurrent TB in HIV coinfection. We highlight the challenges of managing coinfected patients and the increased propensity for the development of drug resistance. We report on the role of various risk factors mediating the development of resistance and subsequent clinical impact. This report underscores the need for structural clinical and adherence interventions for the management of complex treatment and dosing.

SUBMITTER: Naidoo K

PROVIDER: S-EPMC6130302 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Recurrent tuberculosis among HIV-coinfected patients: a case series from KwaZulu-Natal.

Naidoo Kogieleum K Dookie Navisha N Naidoo Kasavan K Yende-Zuma Nonhlanhla N Chimukangara Benjamin B Bhushan Ambika A Govender Dhineshree D Gengiah Santhanalakshmi S Padayatchi Nesri N

Infection and drug resistance 20180905

<h4>Background</h4>Recurrent tuberculosis (TB) following TB treatment completion in HIV-infected individuals remains a major public health burden. We assessed the role of various risk factors in mediating the development of recurrent TB and subsequent resistance to antiretroviral therapy and anti-TB drugs.<h4>Patients and methods</h4>We analyzed secondary demographic, clinical, and laboratory data from medical records of five HIV-infected TB patients enrolled between 2009 and 2014 in a prospecti ...[more]

PMID: 30233220

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Project description:BACKGROUND:Retinal cytomegalovirus (CMV) infection is a common opportunistic infection and remains a significant contributor to visual loss in patients with AIDS. We highlight the poor outcomes of CMV retinitis in three HIV-infected patients who were initiated on antiretroviral therapy (ART). We conducted a retrospective chart review of advanced stage HIV-infected patients with known CMV retinitis.Case 1. A 37-year-old man, with a CD4+ cell count of 35 cells/µL, presented for ART initiation with a 5-month history of visual loss in his left eye. Fundoscopy showed left eye CMV retinitis and right eye HIV retinopathy. ART and 5 months of weekly intravitreal ganciclovir injections (left eye) were commenced. Six-month outcomes included virological suppression, and visual acuity in the right eye of 6/6 and in the left eye of 3/60.Case 2. A 31-year-old woman, with a CD4+ cell count of 39 cells/µL and on tuberculosis therapy, presented for ART initiation. She presented with a 2-month history of decreased visual acuity. Fundoscopy showed bilateral CMV retinitis, which was more pronounced in the left eye. ART and 8 months of intravitreal ganciclovir injections were commenced. Six-month outcomes included virological suppression and visual acuity in the right eye of 6/9, and in the left eye of 6/24.Case 3. A 29-year-old woman, with a CD4+ cell count of 24 cells/µL, who was on tuberculosis therapy and ART, complained of blurred vision at her 2-month ART follow-up visit. Fundoscopy showed bilateral retinal detachment secondary to CMV retinitis. While silicone oil tamponade and subsequent retinectomy successfully repaired the right eye, extensive damage rendered the left eye irreparable. Six-month outcomes included virological suppression, with 6/120 visual acuity in the right eye and complete blindness in the left eye. CONCLUSION:CMV retinitis causes debilitating, permanent sequelae, which is preventable by ART initiation at higher CD4+ cell counts. Despite achieving virological suppression, vision could not be completely restored in these patients, irrespective of the severity of CMV retinitis.

Project description:BackgroundThe current understanding of airborne tuberculosis (TB) transmission is based on classic 1950s studies in which guinea pigs were exposed to air from a tuberculosis ward. Recently we recreated this model in Lima, Perú, and in this paper we report the use of molecular fingerprinting to investigate patient infectiousness in the current era of HIV infection and multidrug-resistant (MDR) TB.Methods and findingsAll air from a mechanically ventilated negative-pressure HIV-TB ward was exhausted over guinea pigs housed in an airborne transmission study facility on the roof. Animals had monthly tuberculin skin tests, and positive reactors were removed for autopsy and organ culture for M. tuberculosis. Temporal exposure patterns, drug susceptibility testing, and DNA fingerprinting of patient and animal TB strains defined infectious TB patients. Relative patient infectiousness was calculated using the Wells-Riley model of airborne infection. Over 505 study days there were 118 ward admissions of 97 HIV-positive pulmonary TB patients. Of 292 exposed guinea pigs, 144 had evidence of TB disease; a further 30 were tuberculin skin test positive only. There was marked variability in patient infectiousness; only 8.5% of 118 ward admissions by TB patients were shown by DNA fingerprinting to have caused 98% of the 125 characterised cases of secondary animal TB. 90% of TB transmission occurred from inadequately treated MDR TB patients. Three highly infectious MDR TB patients produced 226, 52, and 40 airborne infectious units (quanta) per hour.ConclusionsA small number of inadequately treated MDR TB patients coinfected with HIV were responsible for almost all TB transmission, and some patients were highly infectious. This result highlights the importance of rapid TB drug-susceptibility testing to allow prompt initiation of effective treatment, and environmental control measures to reduce ongoing TB transmission in crowded health care settings. TB infection control must be prioritized in order to prevent health care facilities from disseminating the drug-resistant TB that they are attempting to treat.

Project description:ObjectivesResearch on migration and HIV has largely focused on male migration, often failing to measure HIV risks associated with migration for women. We aimed to establish whether associations between migration and HIV infection differ for women and men, and identify possible mechanisms by which women's migration contributes to their high infection risk.DesignData on socio-demographic characteristics, patterns of migration, sexual behavior and HIV infection status were obtained for a population of 11,677 women aged 15-49 and men aged 15-54, resident members of households within a demographic surveillance area participating in HIV surveillance in 2003-04.MethodsLogistic regression was conducted to examine whether sex and migration were independently associated with HIV infection in three additive effects models, using measures of recent migration, household presence and migration frequency. Multiplicative effects models were fitted to explore whether the risk of HIV associated with migration differed for males and females. Further modeling and simulations explored whether composition or behavioral differences accounted for observed associations.ResultsRelative to non-migrant males, non-migrant females had higher odds of being HIV-positive (adjusted odds ratio [aOR] = 1.72; 95% confidence interval [1.49-1.99]), but odds were higher for female migrants (aOR = 2.55 [2.07-3.13]). Female migrants also had higher odds of infection relative to female non-migrants (aOR = 1.48 [1.23-1.77]). The association between number of sexual partners over the lifetime and HIV infection was modified by both sex and migrant status: For male non-migrants, each additional partner was associated with 3% higher odds of HIV infection (aOR = 1.03 [1.02-1.05]); for male migrants the association between number of partners and HIV infection was non-significant. Each additional partner increased odds of HIV infection by 22% for female non-migrants (aOR = 1.22 [1.12-1.32]) and 46% for female migrants (aOR = 1.46 [1.25-1.69]).ConclusionsHigher risk sexual behavior in the context of migration increased women's likelihood of HIV infection.

Project description:SETTING: The dual epidemics of HIV-TB including MDR-TB are major contributors to high morbidity and mortality rates in South Africa. Rifampicin (RIF) resistance is regarded as a proxy for MDR-TB. Currently available molecular assays have the advantage of rapidly detecting resistant strains of MTB, but the GeneXpert does not detect isoniazid (INH) resistance and the GenoTypeMTBDRplus(LPA) assay may underestimate resistance to INH. Increasing proportions of rifampicin mono-resistance resistance (RMR) have recently been reported from South Africa and other countries. OBJECTIVE: This laboratory based study was conducted at NHLS TB Laboratory, Durban, which is the reference laboratory for culture and susceptibility testing in KwaZulu-Natal. We retrospectively determined, for the period 2007 to 2009, the proportion of RMR amongst Mycobacterium tuberculosis (MTB) isolates, that were tested for both RIF and INH, using the gold standard of culture based phenotypic drug susceptibility testing (DST). Gender and age were also analysed to identify possible risk factors for RMR. DESIGN: MTB culture positive sputum samples from 16,748 patients were analysed for susceptibility to RIF and INH during the period 2007 to 2009. RMR was defined as MTB resistant to RIF and susceptible to INH. For the purposes of this study, only the first specimen from each patient was included in the analysis. RESULTS: RMR was observed throughout the study period. The proportion of RMR varied from a low of 7.3% to a high of 10.0% [overall 8.8%]. Overall, males had a 42% increased odds of being RMR as compared to females. In comparison to the 50 plus age group, RMR was 37% more likely to occur in the 25-29 year age category. CONCLUSION: We report higher proportions of RMR ranging from 7.3% to 10% [overall 8.8%] than previously reported in the literature. To avoid misclassification of RMR, detected by the GeneXpert, as MDR-TB, culture based phenotypic DST must be performed on a second specimen, as recommended by the SA NDOH TB guidelines as well as WHO. We suggest that two sputum samples should be obtained at the first visit. The second sputum sample should be stored at 4°C. The latter sample is then readily available for performing additional DST (phenotypic or genotypic) for 2nd lines drugs, resulting in a decreased waiting period for DST results to become available.

Dataset Information

Recurrent tuberculosis among HIV-coinfected patients: a case series from KwaZulu-Natal.

Publications

Recurrent tuberculosis among HIV-coinfected patients: a case series from KwaZulu-Natal.

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