Recurrence of HIV-related tuberculosis in an endemic area may be due to relapse or reinfection

doi:10.1016/0962-8479(94)90008-6

Tubercle and Lung Disease

Volume 75, Issue 3, June 1994, Pages 199-202

Tubercle and Lung Di...

https://doi.org/10.1016/0962-8479(94)90008-6 Get rights and content

Abstract

Setting: Two Research Clinics within Nairobi, Kenya, one in the Infectious Diseases Hospital, the national referral centre for tuberculosis, and one in a community based project in Pumwani district, and the Bacterial Molecular Genetics Unit at the London School of Hygiene and Tropical Medicine.

Objective: To determine whether recurrence of tuberculosis after ‘adequate’ treatment was due to reinfection with a different isolate of Mycobacterium tuberculosis or to relapse of the original infection.

Design: A retrospective comparison by DNA fingerprinting of sets of isolates of M. tuberculosis from patients with recurrence of tuberculosis and in whom isolates from the original episode had been stored was made. Five patients with recurrence of tuberculosis two to nineteen months after adequate treatment and documented clearance of disease were studied.

Results: In one patient, fingerprints of the isolates of M. tuberculosis from the recurrence were quite different to those from the original episode; in the other four, the fingerprints were identical.

Conclusion: Reinfection rather than relapse was the cause of recurrence in at least one patient. The high ‘relapse’ rates seen in HIV-related tuberculosis in Africa may in part be due to increased susceptibility to reinfection and not to treatment failure.

Résumé

Cadre: Deux cliniques de recherche à Nairobi, Kenya: une à l'hôpital des maladies infectieuses (Infectious Diseases Hospital), centre national de référence de la tuberculose, l'autre appartenant à un projet communautaire dans le district de Pumwani, et la ‘Bacterial Molecular Genetics Unit’ au London School of Hygiene and Tropical Medicine.

Objet: Déterminer si la reprise de la tuberculose après un traitement ‘adéquat’ a été due à une réinfection par un autre isolât de Mycobacterium tuberculosis ou à une rechute de l'infection originale.

Schéma: A été effectuée une comparaison rétrospective par ‘fingerprinting’ ADN des sets d'isolats de M. tuberculosis provenant de patients ayant subi une reprise de la tuberculose et dans lesquels des isolats de l'épisode original avait été stockés. Ont été étudiés 5 patients atteints d'une reprise de tuberculose 2 à 19 mois après un traitement adéquat et une résolution documentée de leur maladie.

Résultats: Chez l'un des patients les ‘fingerprints’ des isolats de M. tuberculosis provenant de la reprise étaient totalement différents de ceux de l'épisode original; chez les 4 autres les ‘fingerprints’ ont été identiques.

Conclusion: Une réinfection plutôt qu'une rechute a été la cause d'une reprise de la maladie chez au moins l'un des patients. Les taux élevés de ‘rechutes’ observés dans la tuberculose associée au VIH en Afrique pourraient être en partie dus à une susceptibilité accrue à la réinfection et non pas à un échec du traitement.

Resumen

Marco de referencia: Dos dispensarios de investigación en Nairobi, Kenia: uno en el Hospital de Enfermedades Infecciosas, el centro nacional de referencia para la tuberculosis, el otro en un proyecto comunitario en el distrito de Pumwani, y la Bacterial Molecular Genetics Unit en la London School of Hygiene and Tropical Medicine.

Objetivo: Determinar si la recurrencia de la tuberculosis después de un tratamiento ‘adecuado’ era debido a una reinfección con un aislado diferente de Mycobacterium tuberculosis o a una recaída de la infección original.

Método: Se realizó una comparación retrospectiva por identificación de huellas (fingerprints) del ADN de grupos de aislados de M. tuberculosis provenientes de pacientes con recurrencia de tuberculosis y en quienes se había conservado los aislados del episodio original. Se estudió 5 pacientes con recurrencia de tuberculosis 2 a 19 meses después de un tratamiento adecuado y una evolución bien documentada de la enfermedad.

Resultados: En uno de los pacientes, las huellas de los aislados de M. tuberculosis correspondientes a la recurrencia eran totalmente diferentes de aquéllas del episodio original; en los otros 4 las huellas eran idénticas.

Conclusión: En al menos uno de los pacientes la causa de la recurrencia era una reinfección más bien que una recaída. Las altas tasas de ‘recaídas’ observadas en la tuberculosis asociada al VIH en Africa podrían deberse en parte a una susceptibilidad aumentada a la reinfección y no a un fracaso del tratamiento.

References (15)

P Nunn et al.
Cutaneous hypersensitivity reactions due to thiacetazone in HIV-1 seropositive patients treated for tuberculosis
Lancet
(1991)
P Godfrey-Faussett et al.
Tuberculous pericarditis confirmed by DNA amplification
Lancet
(1991)
A Kochi
Government intervention programs in HIV/tuberculous infection
Bull Int Union Tuberc Lung Dis
(1991)
CJL Murray et al.
Tuberculosis in developing countries: burden, intervention and cost
Bull Int Union Tuberc Lung Dis
(1990)
World Health Organisation
WHO expert committe on tuberculosis. Ninth report
WHO Tech Rep Ser
(1974)
P Nunn et al.
Treating Tuberculosis in HIV-Positive Africans
Lancet
(1991)
JH Perriens et al.
Increased mortality and tuberculosis treatment failure rate among human immunodeficiency virus (HIV) seropositive compared with HIV seronegative patients with pulmonary tuberculosis treated with ‘standard’ chemotherapy in Kinshasa, Zaire
Am Rev Respir Dis
(1991)

There are more references available in the full text version of this article.

Cited by (45)

Exogenous reinfection in tuberculosis
2005, Lancet Infectious Diseases
Citation Excerpt :
Further analysis revealed that four (18%) of these 22 cases occurred in people with previously documented tuberculosis infection or disease, which suggests exogenous reinfection. The development of genotyping methods for M tuberculosis provided a new basis for investigating the transmission of tuberculosis.25–37 One genotyping method for M tuberculosis is based on restriction fragment length polymorphisms (RFLPs) generated by variabilities in both the copy numbers and the chromosomal positions of an insertion sequence (IS6110) among clinical isolates of M tuberculosis.27,28
Whether the development of active tuberculosis in people with previous tuberculous infection represents an episode of endogenous reactivation or exogenous reinfection has been debated for decades. Articles proposing the unitary concept of pathogenesis of tuberculosis in the 1960s initiated a period in which reinfection was considered to be an uncommon cause of tuberculosis. To review evidence demonstrating the occurrence of tuberculosis due to exogenous reinfection, we did a literature search covering publications from 1966 until the present, and found that there was substantial evidence—both experimental and epidemiological—supporting the role of exogenous reinfection in tuberculosis. However, only models based on estimates of the annual risk of infection and the incidence of tuberculosis provided a quantitative estimate of the relative contribution of exogenous reinfection to the burden of tuberculosis. Better estimates of the contribution of exogenous reinfection to new cases of tuberculosis may need to be considered in tuberculosis control strategies.
Molecular epidemiology: A tool for understanding control of tuberculosis transmission
2005, Clinics in Chest Medicine
Recurrent tuberculosis in patients with coinfection by HIV
2003, Revista Clinica Espanola
Analizar e identificar factores asociados a la recurrencia de la tuberculosis (TB) en pacientes infectados por el virus de la inmunodeficiencia humana (VIH).
Se seleccionaron pacientes infectados por VIH diagnosticados de TB entre 1995-2000 y que completaron el tratamiento correctamente. Se compararon aquellos pacientes que presentaron una recurrencia de enfermedad tuberculosa con los que no lo hicieron. Se realizó análisis multivariante por regresión logística para identificar factores asociados a un nuevo episodio de TB.
De un total de 223 pacientes infectados por VIH diagnosticados de TB, 159 (71,3%) completaron adecuadamente el tratamiento y fueron considerados curados. El resto fueron excluidos por fallecer antes de completar el tratamiento (5,8%), perdidos en el seguimiento (11,7%), abandono terapéutico (9,4%) y fracaso terapéutico (1,8%). De los 159 pacientes evaluables, 14 (8,8%) presentaron posterior recurrencia. Los pacientes con TB recurrente presentaron un mayor grado de inmunodepresión, más eventos previos diagnósticos de sida y mayor frecuencia de TB extrapulmonar en el episodio inicial. Tras el análisis multivariante, un recuento de linfocitos CD4 inferior a 100/mm3 en el primer episodio de TB se asoció con enfermedad tuberculosa recurrente (odds ratio [OR]: 4,6; intervalo de confianza [IC] 95%:1,3-18,2). En los episodios recurrentes la mortalidad fue alta (35,7%).
La recurrencia de TB en pacientes coinfectados por VIH ocurre en individuos con inmunodepresión profunda y se asocia a una alta mortalidad.
Analysis and identification of factors associated with the tuberculosis (TB) recurrence in HIV-infected patients.
The HIV-infected patients diagnosed with TB between 1995-2000 and with correct completion of the treatment were selected. There were compared those patients who presented a tuberculous disease recurrence with those which did not presented it. Multivariate analysis was carried out by logistic regression in order to identify factors associated with a new episode of TB.
In the total sample of 223 diagnosed HIV-infected patients with TB, 159 (71.3%) patients completed adequately the treatment and were considered cured. The rest were excluded because of: death before completing the treatment (5.8%), lost in the follow-up (11.7%), therapeutic abandonment (9.4%), and therapeutic failure (1.8%). In the 159 patient final sample, 14 (8.8%) patients presented later recurrence. The patients with recurrent TB presented a greater degree of immunosuppression, more previous complications indicative of AIDS, and greater frequency of extrapulmonary TB in the initial episode. After the multivariate analysis, a count of lymphocytes CD4 lower than 100/mm3 in the first episode of TB was associated with recurrent tuberculous disease (odds ratio [OR]: 4,6; 95% confidence index [CI]: 1,3-18,2). Mortality was high (35.7%) in the patients with recurrent episodes.
The recurrence of TB in patients coinfected by HIV occurs in individuals with profound immunossuppression and is associated to high mortality.
Recurrence in tuberculosis: Relapse or reinfection?
2003, Lancet Infectious Diseases
Citation Excerpt :
Of 27 true relapses in the Italian study,28 15 happened after a first episode caused by a multidrug-resistant strain (MDR); only five initial strains had been fully sensitive. No resistance data are provided by Godfrey-Faussett et al,20 Das et al,21 Sahadevan et al,22 Van Rie et al,25 and Johnson et al.13 In remaining studies, strains were seen to be “most” or all sensitive, with no mention of MDR. Most studies had a median duration of follow-up between 15 and 30 months.
The importance of reinfection as a cause for recurrence of tuberculosis is unclear and has potential public-health implications. We systematically searched published material for studies using DNA fingerprinting to provide data on the issue. Very few studies were designed for that particular research objective and/or report on a sufficient number of observations. Differences in methods—eg, case-definitions—seriously hamper comparisons between studies. The proportion of recurrences due to reinfection ranged between 0% and 100%; however, this figure cannot be a useful indicator since the two causes of recurrence— relapse and reinfection—are essentially independent. Only one study provides an estimate of the incidence of recurrence due to reinfection, indicating its importance for HIV-infected patients in an environment with an unusually high tuberculosis incidence. We argue that apart from extreme situations like this one the problem of recurrence of tuberculosis due to reinfection has few implications for tuberculosis-control programmes.
Relapse and recurrent tuberculosis in the context of a National Tuberculosis Control Programme
2000, Transactions of the Royal Society of Tropical Medicine and Hygiene
The proportion of patients with recurrent tuberculosis (TB) is reported to be increased in TB patients with human immunodeficiency virus (HIV) infection after they have completed treatment. Despite rising HIV seroprevalence amongst TB patients in Malawi, notifications of patients with relapse smear-positive pulmonary TB (PTB) and recurrent smear-negative TB have remained stable during the past 12 years. We suspected that patients with recurrent or relapse TB were being missed under routine programme conditions. Forty-three hospitals in Malawi were visited in 1999, and TB inpatients who had been registered as ‘new’ cases in the TB register and treatment card were interviewed about previous episodes of TB. A previous history of TB was elicited in 94 (7·5%) of 1254 patients who were being treated as new cases. Compared with patients with smear-positive PTB, a previous episode of TB was significantly more common in patients with smear-negative PTB (OR 3·5, [95% CI 2·1–5·7], P < 0·001) and patients with extrapulmonary TB (OR 2·0, [95% CI 1·1–3·7], P < 0·05). Of 94 patients with a previous episode of TB, 76 had completed treatment and 18 had defaulted from treatment during this episode. Patients with recurrent or relapse TB are being incorrectly registered within the Malawi TB Control Programme, and in the case of smear-positive PTB patients this is associated with administration of incorrect treatment. Measures have been put in place to rectify the situation, and further operational research is planned to monitor treatment outcomes of patients with recurrent smear-negative TB.
Relapse, re-infection and mixed infections in tuberculosis disease
2017, Pathogens and Disease

View all citing articles on Scopus

View full text

Original articleRecurrence of HIV-related tuberculosis in an endemic area may be due to relapse or reinfection

Abstract

Résumé

Resumen

Lancet

Lancet

Government intervention programs in HIV/tuberculous infection

Bull Int Union Tuberc Lung Dis

Tuberculosis in developing countries: burden, intervention and cost

Bull Int Union Tuberc Lung Dis

WHO expert committe on tuberculosis. Ninth report

WHO Tech Rep Ser

Treating Tuberculosis in HIV-Positive Africans

Lancet

Increased mortality and tuberculosis treatment failure rate among human immunodeficiency virus (HIV) seropositive compared with HIV seronegative patients with pulmonary tuberculosis treated with ‘standard’ chemotherapy in Kinshasa, Zaire

Am Rev Respir Dis

Original article
Recurrence of HIV-related tuberculosis in an endemic area may be due to relapse or reinfection