Point-of-care management of urogenital Chlamydia trachomatis via Gram-stained smear analysis in male high-risk patients. Diagnostic accuracy and cost-effectiveness before and after changing the screening indication at the STI Clinic in Amsterdam.

OBJECTIVES: To measure the effect of changing the point-of-care (POC) testing algorithm of urogenital chlamydia for all male high-risk patients to those with only symptoms with respect to: diagnostic accuracy, loss to follow-up, correctly managed consultations and costs. METHODS: Retrospective comparison of the diagnostic accuracy and cost-effectiveness of Gram-stained urethral smear analysis for the POC management of urogenital Chlamydia trachomatis infections. Between 2008 and 2009 Gram-stained urethral smear analysis was offered to all men irrespective of symptoms; between 2010 and 2011 only to those with symptoms. The Aptima CT assay was the reference diagnostic test. RESULTS: The number of examined Gram-stained smears in the two periods was respectively 7185 (2008-2009 period) and 18,852 (2010-2011 period). The sensitivity of the Gram stain analysis was respectively 83.8% (95% CI 81.2% to 86.1%) and 91.0% (95% CI 89.5% to 92.3%) (p<0.001). The specificity was respectively 74.1% (95% CI 73.0% to 75.2%) and 53.1% (95% CI 51.8% to 54.4%) (p<0.001). The positive predictive value was low in both periods, respectively 31.7% (95% CI 29.8% to 33.6%) and 35.6% (95% CI 34.1% to 37.1%) (p=0.002), whereas the negative predictive value was high, respectively 97.0% (95% CI 96.4% to 97.4%) and 95.4% (95% CI 94.6% to 96.1%) (p=0.002). The loss to follow-up rate between 2008-2009 and 2010-2011 was, respectively, 1.8% (95% CI 1.0% to 2.9%) vs 2.3% (95% CI 1.7% to 3.0%) (p=0.36). There was a small difference in overtreatment, 68.0% (95% CI 66.0% to 69.8%) vs 64.1% (95% CI 62.6% to 65.5%) (p=0.001). The cost per correctly managed consultation was 14.3% lower in the 2010-2011 period (€94.31 vs €80.82). The percentage of delayed treated infections was significantly lower in the 2008-2009 period (10.5%) compared with the 2010-2011 period (22.8%) (p<0.001). CONCLUSIONS: With a high sensitivity in male high-risk patients, the Gram-stained urethral smear is a useful POC test to detect urogenital C. trachomatis. When offered only to men with urogenital symptoms the specificity decreases but the cost per correctly managed consultation is reduced with 14.3% without a significant difference in loss to follow-up but with a significantly higher rate of delayed treatment.

Comparison of two Gram stain point-of-care systems for urogenital gonorrhoea among high-risk patients: diagnostic accuracy and cost-effectiveness before and after changing the screening algorithm at an STI clinic in Amsterdam.

OBJECTIVES: To compare point-of-care (POC) systems in two different periods: (1) before 2010 when all high-risk patients were offered POC management for urogenital gonorrhoea by Gram stain examination; and (2) after 2010 when only those with symptoms were offered Gram stain examination. METHODS: Retrospective comparison of a Gram stain POC system to all high-risk patients (2008-2009) with only those with urogenital symptoms (2010-2011) on diagnostic accuracy, loss to follow-up, presumptively and correctly treated infections and diagnostic costs. Culture was the reference diagnostic method. RESULTS: In men the sensitivity of the Gram stain was 95.9% (95% CI 93.1% to 97.8%) in 2008-2009 and 95.4% (95% CI 93.7% to 96.8%) in 2010-2011, and in women the sensitivity was 32.0% (95% CI 19.5% to 46.7%) and 23.1% (95% CI 16.1% to 31.3%), respectively. In both periods the overall specificity was high (99.9% (95% CI 99.8% to 100%) and 99.8% (95% CI 99.7% to 99.9%), respectively). The positive predictive value (PPV) and negative predictive value (NPV) before and after 2010 were also high: PPV 97.0% (95% CI 94.5% to 98.5%) and 97.7% (95% CI 96.3% to 98.6%), respectively; NPV 99.6% (95% CI 99.4% to 99.7%) and 98.8% (95% CI 98.5% to 99.0%), respectively. There were no differences between the two time periods in loss to follow-up (7.1% vs 7.0%). Offering Gram stains only to symptomatic high-risk patients as opposed to all high-risk patients saved €2.34 per correctly managed consultation (a reduction of 7.7%). CONCLUSIONS: The sensitivity of the Gram stain is high in men but low in women. When offered only to high-risk patients with urogenital symptoms, the cost per correctly managed consultation is reduced by 7.7% without a significant difference in accuracy and loss to follow-up.

Cutaneous leishmaniasis in three Dutch military cohorts following jungle training in Belize.

Skin lesions occur frequently in travelers to tropical countries. Military personnel acquire skin lesions regularly during jungle training as did Dutch troops who trained in the jungle of Belize in 1998, 2004 and 2009, in an area endemic for cutaneous leishmaniasis. Demographic and clinical data were collected retrospectively. Diagnostic investigations for cutaneous leishmaniasis included Giemsa stain, culture, PCR and NASBA and histopathology of biopsies. Treatment of leishmaniasis was with sodium stibogluconate, given intravenously or intralesionally, the latter with cryotherapy. In 1998 and 2004 cutaneous leishmaniasis due to Leishmania braziliensis and Leishmania mexicana infection was diagnosed in 25 persons out of 99 (attack rate 25.2%) and 14 persons out of 80 (attack rate 17.5%) respectively. In 2009 cutaneous leishmaniasis was not acquired. Skin problems were common during and after jungle training. Cutaneous leishmaniasis was important in the first two cohorts but not observed in the third cohort. Factors that could have played a role in the absence of cutaneous leishmaniasis in the third cohort include variability in transmission and availability of better preventive measures and adherence to these. Sodium stibogluconate treatment, intralesional or intravenous, was effective.

Predictors of the post-thrombotic syndrome with non-invasive venous examinations in patients 6 weeks after a first episode of deep vein thrombosis.

BACKGROUND: Post-thrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT) affecting a large number of patients. Because of its potential debilitating effects, identification of patients at high risk for the development of this syndrome is relevant, and only a few predictors are known. OBJECTIVES: To assess the incidence and potential predictors of PTS. METHODS: We prospectively followed 111 consecutive patients for 2 years after a first episode of objectively documented DVT of the leg. With non-invasive venous examinations, residual thrombosis, valvular reflux, calf muscle pump function and venous outflow resistance were assessed at 6 weeks, 3 months, 6 months, 1 year, and 2 years. The Clinical, Etiologic, Anatomic, and Pathophysiologi classification was used to record the occurrence and severity of PTS. Regression analysis with area under the receiver operating characteristic (ROC) curve was performed to identify potential predictors. RESULTS: The cumulative incidence of PTS was 46% after 3 months, and the incidence and severity did not increase further. Men appeared to be at increased risk as compared with women (risk ratio [RR] 1.4, 95% confidence interval [CI] 0.9-2.2), as were patients over 50 years as compared with younger patients (RR 1.4%, 95% CI 0.9-2.1). Patients with thrombosis localized in the proximal veins at diagnosis had an increased risk of PTS as compared with patients with distal thrombosis (RR 2.3%, 95% CI 1.0-5.6). PTS developed in 32 of 52 patients (62%) with residual thrombosis in the proximal veins 6 weeks after diagnosis, as compared with 17 of 45 patients (38%) without residual proximal thrombosis, leading to a 1.6-fold increased risk (95% CI 1.0-2.5). The presence of valvular reflux in the superficial veins was also a predictor at 6 weeks, with a 1.6-fold increased risk as compared with patients without superficial reflux (95% CI 1.1-2.3). A multivariate analysis of these predictors yielded an area under the ROC curve of 0.72 (95% CI 0.62-0.82). CONCLUSIONS: PTS develops in half of all patients within 3 months, with no further increase being seen up to 2 years of follow-up. Male sex, age over 50 years, proximal localization of the thrombus at entry, residual proximal thrombosis and superficial valvular reflux at 6 weeks seem to be the most important predictors of PTS in patients with a first episode of DVT. Duplex scanning 6 weeks after diagnosis appears to be clinically useful for the identification of patients at risk of PTS.

Miltefosine treatment of Leishmania major infection: an observational study involving Dutch military personnel returning from northern Afghanistan.

In a retrospective, observational study involving 34 patients with Leishmania major infection, 31 of whom had experienced unsuccessful treatment with intralesional antimony (ilSb(v)), miltefosine proved effective. Thirty patients experienced cure after receipt of miltefosine, 3 after receipt of additional ilSb(v), and 1 after 28 daily intravenous injections of antimony. Temporary diminution of ejaculate volume was reported by 21 patients.

Cutaneous leishmaniasis with lymphadenopathy due to Leishmania donovani.

We describe a case of cutaneous leishmaniasis with lymphadenopathy due to Leishmania donovani, which was successfully treated with oral miltefosine. Given the increased prevalence of travelling, patients presenting with lymph-node enlargement should have leishmaniasis included in the differential diagnosis even in the absence of typical ulceration.

Risk factors for post-thrombotic syndrome in patients with a first deep venous thrombosis.

BACKGROUND: Post-thrombotic syndrome (PTS) is a chronic complication of deep venous thrombosis (DVT). OBJECTIVES: To determine the risk of PTS after DVT and to assess risk factors for PTS. METHODS: Patients were recruited from the Multiple Environmental and Genetic Assessment (MEGA) study of risk factors for venous thrombosis. Consecutive patients who suffered a first DVT of the leg were included in a follow-up study. All patients completed a questionnaire and DNA was obtained. PTS was ascertained in a structured interview using a clinical classification score. RESULTS: The 1-year cumulative incidence of PTS was 25% and 7% for severe PTS. Elastic compression stockings were prescribed in 1412 (85%) patients. The majority used their stockings every day. Women were at an increased risk compared with men [risk ratio (RR) 1.5, 95% confidence interval (CI) 1.3-1.8]. Similarly, obese patients had a 1.5-fold increased risk of PTS compared with normal weight patients (RR 1.5, 95% CI 1.2-1.9), with a 1-year cumulative incidence of 34% compared with 22%. Patients who already had varicose veins had an increased risk (RR 1.5, 95% CI 1.2-1.8) of PTS. DVT in the femoral and iliac vein was associated with a 1.3-fold increased risk of PTS compared with popliteal vein thrombosis (RR 1.3, 95% CI 1.1-1.6). Patients over 60 years were less likely to develop PTS than patients below the age of 30 (RR 0.6, 95% CI 0.4-0.9). Malignancy, surgery, minor injury, plaster cast, pregnancy or hormone use did not influence the risk of PTS neither did factor (F)V Leiden nor the prothrombin 20210A mutation. CONCLUSIONS: PTS is a frequent complication of DVT, despite the widespread use of elastic compression stockings. Women, obese patients, patients with proximal DVT and those with varicose veins have an increased risk of PTS, whereas the elderly appeared to have a decreased risk.

Erythema nodosum leprosum in Nepal: a retrospective study of clinical features and response to treatment with prednisolone or thalidomide.

INTRODUCTION: Erythema nodosum leprosum (ENL) is an inflammatory reaction, which may occur in the course of leprosy and may result in nerve function impairment and subsequent disability. METHODS: This retrospective study explores demographic and disease specific parameters. Severity of ENL was assessed using the Reaction Severity Scale (RSS). Records of 94 patients were reviewed. The study reports also on the treatment of 76 of these patients who were treated with prednisolone alone or thalidomide in addition to prednisolone. RESULTS Thirty percent of patients presented with ENL at time of diagnosis; 41% developed ENL-reaction in the first year of MDT. Forty-eight percent of patients were treated for ENL-reaction for less than 12 months; 13% for more than 5 years. High RSS-scores correlated with a longer duration of treatment. In group A (prednisolone) 51.7% and in group B (prednisolone and thalidomide) 76.6% of patients were male. Age, leprosy classification, delay of multidrug treatment (MDT) and interval between MDT and first ENL-symptoms did not differ significantly in both groups. Median duration of ENL-treatment was 15 months in group A versus 38 months in group B (P < 0.001). At the start of treatment, ENL-reaction was less severe in group A (RSS = 12) than in group B (RSS = 18; P = 0.003). DISCUSSION: ENL-symptoms may be of help in the early diagnosis and adequate treatment of ENL. Characterisation of (sub) groups of patients with ENL based on presence and severity of symptoms is important for future prospective studies to better evaluate the efficacy of interventions.

A clinical and radiological follow-up study in leprosy patients with asymptomatic neuropathic feet.

OBJECTIVES: An MRI study done in 2000 on 10 leprosy patients with neuropathic feet, without clinical complications such as ulcerations, osteomyelitis or Charcot deformities revealed abnormalities in nine patients, with degradation, interruption of subcutaneous fat and effusion/synovitis, all located in the first metatarsophalangeal (MTP) region. Since these MRI abnormalities may precede clinical complications of the foot, a follow-up study was performed. DESIGN: A new evaluation was based on a clinical examination and an MRI of the same patients who participated in the initial study. RESULTS: Four patients were lost to follow-up. Average follow-up period was 4-6 years. MRI abnormalities in the MTP 1 region in the first study were no longer visible in three patients, but were still present in two patients. In six patients new MRI findings were found, without clinical evidence of ulceration, osteomyelitis or Charcot deformity. No relationship was found between MRI findings in the MTP 1 region at the start of the study and the development of foot ulcers, callus or skin fissures in the MTP 1 region during follow-up. CONCLUSION: MRI findings of interruption and infiltration of the subcutaneous fat in leprosy patients with uncomplicated neuropathic feet do not necessarily have any clinical implication for the development of future foot problems.

Treatment assessment by monitoring parasite load in skin biopsies from patients with cutaneous leishmaniasis, using quantitative nucleic acid sequence-based amplification.

BACKGROUND: Current diagnostic methods for cutaneous leishmaniasis (CL) have low sensitivity or are not useful for treatment follow-up. We previously described the quantitative nucleic acid sequence-based amplification (QT-NASBA) method as a sensitive and specific assay for detection and quantification of Leishmania parasites in skin biopsies. This assay could be a valuable instrument for monitoring response to treatment of CL and identifying treatment failures at an early stage. AIM: QT-NASBA results of skin biopsies at the end and 6 weeks after treatment from patients with proven CL on various treatment regimens were compared with clinical outcome. METHODS: The QT-NASBA assay measured the parasite load in skin biopsies before, at the end and 6 weeks after treatment. The results were compared with treatment outcome (clinical cure, delayed healing response or treatment failure) up to 6 months after treatment. RESULTS: In total, 137 skin biopsies were obtained from 53 patients. A positive QT-NASBA result 6 weeks after treatment was significantly associated with treatment failure/delayed healing up to 6 months (P < 0.001). The positive predictive value (PPV) was 100% and the negative predictive value (NPV) was 92% (95% CI 82-100%). QT-NASBA results at the end of treatment and clinical outcome showed a less significant association (P < 0.05), with a PPV of 46% (95% CI 16-75% and an NPV of 89% (95% CI 79-99%). CONCLUSIONS: The QT-NASBA assay is a useful instrument to monitor parasite load in skin biopsies of patients with CL 6 weeks after treatment and can help to predict clinical outcome.

[Diagnostic image (325). A traveller with a chronic wound]. / Diagnose in beeld (325). Een reiziger met een chronische wond.

A 43-year-old man with a chronic leg ulcer was diagnosed with Buruli-ulcer, caused by Mycobacterium ulcerans, probably contracted in Australia.

[Contributions of the Netherlands and its colonies to the knowledge of the cause of leprosy in the 19th century]. / Bijdragen van Nederland en zijn koloniën aan de kennis over de oorzaak van lepra in de 19e eeuw.

OBJECTIVE: To determine the Dutch contributions to the formulation of the concept that leprosy is an infectious disease. DESIGN: Literature study. METHOD: A search for relevant publications was made in the Nederlands Tijdschrift voor Geneeskunde (Dutch journal of Medicine; NTvG) and the Geneeskundig Tijdschrift voor Nederlandsch-Indië (Medical Journal of the Dutch Indies; GTNI) with the aid of the search terms 'lepra [leprosy]', 'lepra Arabum [Arab leprosy]', 'melaatsheid [leprosy]' and 'elephantiasis Graecorum [Greek elephantiasis]'. In addition, on the basis of references in the publications in the NTvG and the GTNI, as well as via searches in the catalogues of the Royal Library in The Hague and the libraries of Dutch universities, an inventory was made of the Dutch medical dissertations and other monographs on leprosy, as well as the medical historical review articles, from the 19th century. RESULTS: For a long time, physicians described the aetiology of leprosy in terms of 'a substrate' to which all sorts of mixtures of infection, heredity and hygiene contributed. From the middle of the 19th century onwards, this explanatory model with multiple possible solutions gave way to a controversy between two explanatory models: heredity as an 'anti-contagious' principle versus contagiosity. These two explanatory models were mutually exclusive in their universal aspirations. The debate in the Netherlands took place in the field of tension between European concepts on the one hand and on the other hand ideas and practices resulting from the interaction between the Netherlands and its colonies. Inspired in part by the writings of the Dutch physician C L Drognat Landré, who based his contagion theory on observations in Surinam, the Norwegian G. H. A. Hansen discovered the leprosy bacillus in 1873. It was not until 1897, at the international leprosy conference in Berlin, however, that consensus was to be reached on leprosy being an infectious disease. CONCLUSION: An essential contribution to the development of the contemporary ideas as to the cause of leprosy was made from the Netherlands.

[Specific dermatoses of pregnancy]. / Specifieke zwangerschapsdermatosen.

Dermatoses related to pregnancy or the postpartum period are known as the specific dermatoses of pregnancy. These dermatoses include (a) pemphigoid gestationis (synonym: herpes gestationis), (b) polymorphic eruption of pregnancy (synonym: pruritic urticarial papules and plaques of pregnancy; PUPPP), (c) prurigo of pregnancy and (d) pruritic folliculitis of pregnancy. Of these disorders, only pemphigoid gestationis has a known cause: an allogeneic immune reaction of the mother to the placental basal membrane. Itching or an itchy skin eruption is often the main symptom ofa dermatosis of pregnancy. During the diagnostic process, the possibility of a pre-existing or de novo skin disorder unrelated to the pregnancy should be considered. Correct diagnosis is important for the choice of treatment and for the prognosis of mother and child, because some dermatoses of pregnancy, such as pemphigoid gestationis, constitute a health risk.

Quantification of the response to miltefosine treatment for visceral leishmaniasis by QT-NASBA.

A male patient with psoriatic arthritis and visceral Leishmania infantum infection was treated with oral miltefosine 50 mg three times a day for 4 weeks at the Academic Medical Center, Amsterdam, The Netherlands. Miltefosine plasma concentrations were measured with liquid chromatography/mass spectrometry. The parasite load was followed by quantitative nucleic acid sequence-based amplification (QT-NASBA) assay in blood. Miltefosine elicited a prompt therapeutic effect. After an initial worsening of symptoms and an increase of QT-NASBA values during the first week, recovery was rapidly achieved. QT-NASBA values declined exponentially and were negative after 6 weeks. Miltefosine plasma concentrations continued to accumulate during the 4 weeks of treatment. The terminal elimination half-life was 14.8 days.

Changing pattern of imported cutaneous leishmaniasis in the Netherlands.

Cutaneous leishmaniasis (CL) in western countries seems to be appearing more frequently. Our aim was to determine if there has been a shift in countries where CL is acquired and whether the incidence has changed, and to assess current diagnostic procedures and treatment modalities. In a retrospective study medical records of patients with the diagnosis of CL at the Departments of Tropical Dermatology and Tropical Medicine, Academic Medical Center, Amsterdam, the Netherlands, from 1990 to 2000 were analysed. CL was diagnosed in 78 patients. The majority was acquired in Belize, Surinam, French Guyana and Bolivia. Giemsa stains were positive for the parasite in impression smears from 43% and in biopsies from 71%. Seventy-eight per cent of cases were culture-positive and 89% were PCR-positive. Sixty-two patients were treated systemically: pentavalent antimony (32), pentamidine isetionate (11), itraconazole (19), and 13 locally, the majority with a combination of cryosurgery and intralesional pentavalent antimony. Imported CL is becoming more frequent, with South and Middle American countries being important sources of infection. Multiple tests, of which PCR is the most sensitive, are required to confirm the diagnosis. Systemic treatment was given to the majority of the patients.

Population survey to determine risk factors for Mycobacterium leprae transmission and infection

Background: Not every leprosy patient is equally effective in transmitting Mycobacterium leprae. We studied the spatial distribution of infection (using seropositivity as a marker) in the population to identifity which disease characteristics of leprosy patients are important in transmission. Methods: Clinical data and blood samples for anti-M.leprae ELISA were collected during a cross-sectional survey on five Indonesian islands highly endemic for leprosy. A geographic information system (GIS) was used to define contacts of patients. We investigated spatial clustering of patients and seropositive people and used logist regression to determine risk factors for seropositivity. Results: Of the 3986 people examined for leprosy, 3271 gave blood. Seroprevalence varied between islands (1.7-8.7%) and correlated significantly with leprosy prevalence. Five clusters of patients and two clusters of seropositives were detected. In multivariate analysis, seropositivity significantly differed to be the best discriminator of contact groups with higher seroprevalence: contacts of seropositive patients had an adjusted odds ratio (aOR) of 1.75 (95% CI: 0.92-3,31). This increased seroprevalence was strongest for contact groups living _< 75 metres of two seropositive patients (aOR:3.07;95%CI:1.74-5.42). Conclusions: In this highly endemic area for leprosy, not only household contacts of seropositive patients, but also persons living in the vicinity of seropositive patient were more likely to harbour antibodies against M.leprae. Through measuring the serological status of patients and using a broader definition of contacts, higher risk groups can be more specifically identified

Risk factores for developing leprosy -A population-based cohort study in Indonesia

This study identified risk factors for developing leprosy through yearly incidence rates in five island populations. Personal factors, like age, sex, household size and the presence of M.leprae-specific antibodies as well as contact were studied. Of the 94 index patients (patients diagnosed in 2000) 43 (46%) were classified as multibacillary (MB), 17 (19%) were seropositive and 6 (7%) presented M.leprae DNA in nasal swabs as determined by polumerase chain reaction (PCR). All PCR positive patients were also seropositive. Forty-four of the 4903 persons initially without symptoms of leprosy developed leprosy in almost four years follow-up, giving an incidence rate of 2.98 per 1000 person-years. Men had a 2.2 times higher risk (95% Confidence Interval [CI]: 1.2-4.1) to developd leprosy than women. Persons living in households of more than 7 household members. Persons who were seropositive in 2000 had a 3.7 times higher risk (95% CI:1.1-12.4) than seronegative persons. Household contacts of MB patients had an adjusted hazard ratio (aHR) of 4.6 (95% CI:1.6-12.9) and household contacts of PCR positive patients an aHR of 9.36 (95% CI: 2.5-34.9) compared to non-contacts. Patients with PCR positive nasal swabs, suggesting nasal excretion of M.leprae, are probably the patients with the highest transmission patential. Since all index patients who were PCR positive were also seropositive, serology semms an adequate tool to identify these patients. Preventing seropositive persons to become seropositive patients and thus the main source of infection may break the chain of transmission

[Cutaneous myiasis caused by a double infestation with larvae of Dermatobia hominis and Cochliomyia hominivorax]. / Cutane myiasis door een dubbelinfestatie met larven van Dermatobia hominis en Cochliomyia hominivorax.

In a 51-year-old man who had visited Surinam, cutaneous myiasis was diagnosed, caused by simultaneous infestation with the larvae of two different species of flies: Dermatobia hominis and Cochliomyia hominivorax. On his right lower arm the man had two solitary, furuncle-like lesions with a central breathing hole. Two days after these holes had been occluded with vaseline, two white larvae of D. hominis emerged. On both ankles the man had large, undermined ulcers containing hundreds of creeping larvae about 2 cm in length with a salmon-like colour: C. hominivorax. The larvae were removed from the ulcers by hand and by rinsing with physiological saline, after which the wounds healed rapidly. Myiasis is seen in the Netherlands mostly in people returning from a holiday in myiasis-endemic areas.

Serial measurement of serum cytokines, cytokine receptors and neopterin in leprosy patients with reversal reactions.

Serum levels of cytokines (IL-4, IL-5, IFN-gamma, TNF-alpha), cytokine receptors (TNFR I and II) and one monokine (neopterin) were estimated in seven leprosy patients to establish disease associated markers for reversal reactions (RR). Sera were collected at diagnosis of leprosy, at the onset of reversal reaction and at different time points during and at the end of prednisone treatment of reactions. It was expected that the serum cytokine and monokine profile before and at different time points during reactions would provide guidelines for the diagnosis and monitoring of reversal reactions in leprosy. The cytokines and cytokine receptors were measured by ELISA, whereas a radioimmunoassay was used for neopterin measurement. Six of the seven patients showed increased levels of neopterin either at the onset of RR or 1 month thereafter, and levels declined on prednisone treatment to that seen at the time of diagnosis without reactions. No consistent disease associated cytokine profile was observed in these patients. Interestingly, serum TNF-alpha levels were increased in the same patients even after completion of prednisone treatment, indicating ongoing immune activity. In conclusion, this study demonstrates that despite cytokines levels in leprosy serum being inconsistent in relation to reversal reactions, serum neopterin measurement appears to be an useful biomarker in monitoring RR patients during corticosteroid therapy.