Chemoprophylaxis is Effective in the Prevention of Leprosy in Endemic Countries: a Systematic Review and Meta-Analysis

Smith, Cairns; Smith, W. C.

doi:10.1053/jinf.2000.0698

Cited by 75 publications

(39 citation statements)

References 13 publications

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“…The evidence showed that chemoprophylaxis against leprosy is an effective way to reduce the incidence of leprosy in household contacts (Smith & Smith 2000). A more recent publication dealt with a single centre, double blind, cluster randomized, placebo-controlled trial carried out in two districts of northwest Bangladesh, which enrolled 28,092 close contacts of 1,037 patients with newly diagnosed leprosy.…”

Section: Discussionmentioning

confidence: 99%

Leprosy reactions: the effect of gender and household contacts

Mastrangelo

Neto²,

Silva³

et al. 2011

Mem. Inst. Oswaldo Cruz

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Although leprosy is a chronic infectious disease, it may be considered an immunologic disease too (Lupi et al. 2006, Naafs 2006. In fact, a noticeable proportion of leprosy patients suffer from immunologic hypersensitivity reactions at any given time in the disease process, including before, during and after treatment. These adverse immunological reactions are now the most significant issue in the management of leprosy.There are two primary types of leprosy reaction: (i) type 1 reaction: also called reversal reaction occurs only in patients with borderline disease and is associated with oedema, increased erythema, potential ulceration of existing skin lesions and nerve damage, which is the major concern and (ii) type 2 reaction: also called erythema nodosum leprosum, is a systemic inflammatory response which may manifest in fever, arthralgias, myalgias, anorexia, erythematous sparse tender nodules on the extensor surfaces of the extremities. Conjunctivitis, neuritis, keratitis, iritis, synovitis, nephritis, hepatosplenomegaly, orchitis and lymphadenopathy may also occur. Although several new drugs have been studied and found to be of some use, corticosteroids continue to be the mainstay treatment in the management of leprosy reactions. Unfortunately, the chronic administration of corticosteroids induces either minor (moon face, severe fungal skin infections, severe acne and gastric pain needing antacid) or major side effects (psychosis, peptic ulcer, glaucoma, cataracts, diabetes, hypertension and steroid dependency) resulting in permanent damage.Various host-related factors have been reported as risk factors for leprosy reactions, such as female gender, pregnancy and breastfeeding, suffering from lepromatous leprosy, presence of a positive bacterial index, undergoing multi-drug therapy for leprosy, other medications, vaccinations, infections, injury and physical and mental stress (review in Mastrangelo et al. 2008). It has been reported that these factors are presumed to cause the multiplication of dormant viable Mycobacterium leprae (which are known to persist for many years in Schwann cells or in fibrous tissue without producing any ill effects) and the release of microbacterial antigens in the local tissues (Britton & Lockwood 2004).In endemic areas, it was found that: M. leprae survives outside of the human body, healthy individuals harbour M. leprae bacilli in the nasal cavity and microorganisms can be subsequently released into the environment and there is widespread subclinical transmission of M. leprae with transient infection of the nose resulting in the development of a mucosal immune response (review in Mastrangelo et al. 2008).

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Section: Discussionmentioning

confidence: 99%

Leprosy reactions: the effect of gender and household contacts

Mastrangelo

Neto²,

Silva³

et al. 2011

Mem. Inst. Oswaldo Cruz

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“…Studies on dapsone prophylaxis also showed that this was more effective when given as a blanket treatment rather than only to household contacts. 5 A possible explanation of these findings could be that by the time the prophylaxis is given the potential bacillary load in physically close contacts, closely related contacts, seropositive contacts, and contacts of patients with multibacillary disease is on average already too high to be eliminated by a single (or double, in Indonesia two doses were given) dose of rifampicin. This possibly higher average bacterial load could be caused either by a higher exposure (household contacts, contacts of patients with multibacillary disease) or by a higher vulnerability (genetic make-up, partly reflected in seropositivity, male sex).…”

Section: Discussionmentioning

confidence: 99%

“…This efficacy at two years is similar to that found in a meta-analysis of dapsone trials, although in those trials dapsone was given for 1-5 years. 5 The finding of single dose rifampicin as a cheap and practical preventive intervention for contacts of patients with leprosy in leprosy control programmes is a promising. The effect is not consistent in all subgroups, requiring further study before recommendations can be made for routine implementation.…”

Section: Discussionmentioning

confidence: 99%

“…3 4 A meta-analysis of the studies on chemoprophylaxis with prolonged administration of these drugs estimated an overall efficacy of about 60%. 5 The efficacy in household contacts ranged from 34-54%, 3 6 whereas in the community intervention trial it was 91%. 7 The disadvantages of dapsone as a chemoprophylactic agent are the development of drug resistance and the lack of patient compliance because of the need for administration over a long period.…”

Section: Introductionmentioning

confidence: 99%

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Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomised controlled trial

Moet

Pahan²,

Oskam

et al. 2008

BMJ

207

153

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Objective To determine the effectiveness of chemoprophylaxis using a single dose of rifampicin to prevent leprosy in close contacts. Design Single centre, double blind, cluster randomised, placebo controlled trial. SettingLeprosy control programme in two districts of northwest Bangladesh with a population of more than four million. Participants28 092 close contacts of 1037 patients with newly diagnosed leprosy. 21 711 contacts fulfilled the study requirements. Interventions A single dose of rifampicin or placebo given to close contacts in the second month of starting the index patient's treatment, with follow-up for four years. Main outcome measure Development of clinical leprosy. Results 18 869 of the 21 711 contacts (86.9%) were followed-up at four years. Ninety one of 9452 contacts in the placebo group and 59 of 9417 in the rifampicin group had developed leprosy. The overall reduction in incidence of leprosy using a single dose of rifampicin in the first two years was 57% (95% confidence interval 33% to 72%). The groups did not differ between two and four years. The overall number needed to treat (NNT) to prevent a single case of leprosy among contacts was 297 (95% confidence interval 176 to 537). Differences were found between subgroups at two years, both in reduction of incidence and in NNT. Conclusion A single dose of rifampicin given to contacts of patients with newly diagnosed leprosy is effective at preventing the development of clinical leprosy at two years. The effect was maintained, but no difference was seen between the placebo and rifampicin groups beyond two years. Trial registration Current Controlled Trials ISRCTN61223447.

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“…It offers tools for improved leprosy control by refocusing control activities from the current blanket approach to a more focused and specific approach that includes intervention strategies applied to defined contacts. In their meta-analysis, Smith et al (12) have shown that applying chemoprophylaxis to contacts is an effective way to reduce the incidence of leprosy and is more cost-effective when used for household contacts than for communities as a whole. Prophylactic treatment of contacts of incident patients may become an even more feasible approach under routine control program conditions when high-risk contacts can be identified and the expenditure of limited resources can be focused.…”

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confidence: 99%

Prospective Study of Serological Conversion as a Risk Factor for Development of Leprosy among Household Contacts

Douglas

Cellona

Fajardo

et al. 2004

Clin Vaccine Immunol

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Although the prevalence of leprosy has declined over the years, there is no evidence that incidence rates are falling. A method of early detection of those people prone to develop the most infectious form of leprosy would contribute to breaking the chain of transmission. Prophylactic treatment of serologically identified high-risk contacts of incident patients should be an operationally feasible approach for routine control programs. In addition, classification of high-risk household contacts will allow control program resources to be more focused. In this prospective study, we examined the ability of serology used for the detection of antibodies to phenolic glycolipid I of Mycobacterium leprae to identify those household contacts of multibacillary leprosy patients who had the highest risk of developing leprosy. After the start of multidrug therapy for the index case, a new case of leprosy developed in one in seven of the 178 households studied. In households where new cases appeared, the seropositivity rates were significantly higher (P < 0.001) than those in households without new cases. Seropositive household contacts had a significantly higher risk of developing leprosy (relative hazard adjusted for age and sex [aRH], 7.2), notably multibacillary leprosy (aRH ‫؍‬ 24), than seronegative contacts.

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Chemoprophylaxis is Effective in the Prevention of Leprosy in Endemic Countries: a Systematic Review and Meta-Analysis

Cited by 75 publications

References 13 publications

Leprosy reactions: the effect of gender and household contacts

Leprosy reactions: the effect of gender and household contacts

Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomised controlled trial

Prospective Study of Serological Conversion as a Risk Factor for Development of Leprosy among Household Contacts

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