Scrub Typhus: An Emerging Neglected Tropical Disease in Nepal.

BACKGROUND: Scrub typhus is a neglected tropical disease and is under reported from Nepal. The objective of this study was to investigate the sero-epidemiology of scrub typhus in patients suffering from acute febrile illness. METHODS: A total of 434 specimens collected from July to November 2015 at National Public Health Laboratory (NPHL) were investigated for detection of immunoglobulin M (IgM) antibody to Orientiatsutsugamushi.The Scrub Typhus Detect TM kit (InBios, USA) was used to detect the antibodies to O.tsutsugamushi in human serum. Randomly selected 10% positive specimens were used for confirmation by dot- enzyme-linked immunosorbent assay and indirect immunofluorescence assay. RESULTS: Of the total, 175 (40.3%) were positive for IgM antibodies to O. tsutsugamushi. Positive results of scrub typhus were highest among female in 11-20 year followed by males in 41-50 years age group. The IgM antibodies to O. tsutusugamushi were positive in specimens of various geographical regions including 30 districts of Nepal. Positive cases were found in various ecological regions of Nepal. CONCLUSIONS: Scrub typhus is one of the neglected tropical diseases in Nepal. Patients with acute febrile illness should be investigated for scrub typhus with high priority. There is an urgent need of reliable and affordable diagnostic tests at all level of health facilities of Nepal. Surveillance and public health awareness about the disease transmission and preventive measures needs to be initiated.

Outbreak Investigation of Influenza in Pajaru VDC of Jajarkot District of Nepal.

BACKGROUND: An outbreak investigation study was conducted in Pajaru, one of the initially affected Village Development Committees (VDCs) of the Jajarkot district in Nepal following an outbreak of respiratory illness in early 2015. The objectives of this study were to identify the cases and magnitude of the outbreak. METHODS: A cross-sectional study was carried out in mid-April 2015 covering five most affected wards of Pajaru VDC to assess the patients using standard case definition for Influenza like Illness (ILI). Throat and nasal swabs were collected and sent to the National Influenza Center (NIC) in Kathmandu for laboratory confirmation. RESULTS: The throat swab samples tested at NIC found Influenza A H1N1 pdm09. The attack rate was calculated to be 3% in ward number 9 and 41% in ward number 8. Wavelength of the infection was nearly two weeks in both the wards. Nearly 54% of the specimens were positive for Influenza A H1N1 pdm09. There was no ILI case fatality in the study area. Children aged 0-15 years were most affected. Majority of the patients presented with symptoms of fever, cough and sore throat. CONCLUSIONS: There was gradual decline in the number of cases in all five wards suggestive of development of natural immunity in the community. True severity of the outbreak was not accurately reflected as compared to media reports.

Monitoring the durability of long-lasting insecticidal nets in field conditions in Nepal.

Understanding and improving the durability of long-lasting insecticidal nets (LLINs) in the field is critical for the success of malaria prevention using mosquito nets, as well as contributing to procurement decisions based on the number of years of protection, rather than the current practice of unit cost. Using the recently published guidelines from the World Health Organization (WHO) some progress has been made in the monitoring and assessment of performance of nets in the field. This paper describes the protocol of an ongoing retrospective study of the attrition rate, physical integrity and bioefficacy of three polyester LLIN products that were distributed during 2010 to 2013 in Nepal. It is hoped that robust and auditable data on net survival (physical integrity and bioefficacy) of these three brands in different environments will assist the Nepal National Malaria Control Programme in planning future LLIN-replacement strategies, including behaviour-change communication about LLIN care and maintenance. The advantages and disadvantages of prospective and retrospective cross-sectional approaches are discussed, including appropriate strategies to validate the timing for mass distribution of nets. Similar studies should be done in other countries to (i) track LLIN durability to support management of resupply, and (ii) inform procurement decisions at the global level. New, more predictive, textile laboratory testing is also urgently needed.

Statins and cardiovascular risk in rheumatic diseases.

Chronic inflammatory rheumatic diseases are associated with an increased risk of cardiovascular (CV) atherosclerotic events. The inflammatory state, which is the hallmark of chronic rheumatic diseases, is the important driving force for accelerated atherogenesis. Since the control of traditional risk factors alone is insufficient in reducing the risk, much attention has been directed towards the potential use of statins. Statins, a family of drugs that suppress cholesterol biosynthesis by inhibiting the hydroxymethyl glutaryl coenzyme A reductase, have been shown to significantly reduce CV-related morbidity and mortality. In addition to lower lipid levels, several non-lipid lowering pleiotropic effects, including anti-inflammatory and immunomodulatory activities, make statins potential therapeutic agents in chronic rheumatic diseases. However, lipid metabolism in chronic rheumatic diseases is complex, since inflammatory states can induce alterations in lipid levels and function, so that cholesterol target levels from general guidelines may not be adequate in chronic inflammatory rheumatic diseases. Larger trials are needed to refine the precise benefits and health-utility associated with this therapy.

Systemic sclerosis and cancer.

To review recent advances and current controversies on the association between systemic sclerosis (SSc) and cancer, PUBMED was searched from 1966 to the present using the terms: systemic sclerosis, cancer, morphoea, sclerotic diseases. Malignancies, mainly in lung and breast, coexist with idiopathic SSc or with SSc-like disorders, but not with localized forms of scleroderma (morphoea), with the exception of squamous cell carcinoma in patients with pansclerotic morphoea and skin ulcers. The mechanisms connecting SSc and malignancies are unknown. The occurrence of different cancer types with SSc or SSc-like disorders suggest different underlying mechanisms, including altered immune response, common genetic and environmental links, disease-dependent factors, tumor-derived biologic substances and therapies. The process of sclerosis itself may favour cancer in certain sites, and a reaction between T cells and neoantigens formed during irradiation has been suggested to explain the frequent development of morphoea after breast irradiation. Radiotherapy, especially when used for breast cancer, may trigger idiopathic SSc or morphoea and influence the severity of preexisting SSc, with the consequence that SSc is considered a relative contraindication to breast radiotherapy. In conclusion, cancer and SSc may be associated, but it is still controversial as to whether there is a causal relationship. Continuing interest in these associations, in particular in the different modalities of associations, may help to understand the underlying biological mechanisms and to identify patients at risk.

The safety of anti-TNF agents in the elderly.

Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis are commonly thought of as inflammatory diseases that affect younger individuals. Although the initial presentation of these diseases is common in a patients twenties or thirties, they usually persist for the duration of the patients life. In addition, up to one-third of patients with RA have disease onset after 60 years of age. Anti-TNF-a therapies now have well-recognized safety profiles that have been demonstrated in the usual clinical trial populations for these diseases, but such populations under-represent patients > or =65 years of age. This retrospective study aims to determine the safety profiles for etanercept, infliximab and adalimumab in patients of 65 years or more, undergoing anti-TNF treatment for an active inflammatory disease such as rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis, or skin disease like psoriasis. Our data show that admitting elderly patients into anti-TNF therapeutic regimens is a safe option and that it grants these patients access to the best current therapeutic option, possibly leading to better disease outcome. Quality of life in elderly patients affected by arthritis or psoriasis, often reduced by comorbidities, is as important as quality of life in younger patients. Applying the recommended screening before using biological treatment helps to reduce adverse events related to the therapy, and the application of the same screening in elderly patients seems to lead to comparable results.

Successful treatment with etanercept of a patient with psoriatic arthritis after adalimumab-related hepatotoxicity.

Inhibitors of tumor necrosis factor (TNF) alpha (infliximab, etanercept, adalimumab) are nowadays widely used for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), not responding to conventional therapies. Anti-TNF alpha drugs have demonstrated great efficacy in slowing the disease, however, to date, concern still remains regarding acute and long-term toxicity related to TNF block. Increase in liver tests may be observed during treatment with anti-TNF agents, more often related to concomitant drugs (i.e. NSAIDS, methotrexate) or to reactivation of chronic HBV or HCV infections. However, liver damage directly induced by the drug has been described in patients treated with infliximab or adalimumab. To our knowledge, no cases of liver injury closely related to etanercept have been reported so far. We report the case of a patient with PsA who presented liver dysfunction during adalimumab, subsequently successfully treated with etanercept.

Myocardial involvement in systemic sclerosis.

OBJECTIVE: To identify clinical and/or laboratory characteristics that could be risk factors for myocardial microvascular involvement in patients with SSc. METHODS: Twenty-one SSc patients, clinically silent for cardiovascular disease, were consecutively evaluated for myocardial perfusion defects through 99m-Tc sestamibi gated myocardial perfusion SPECT with a stress-rest protocol. RESULTS: Eight patients (38%) had myocardial perfusion defects. Perfusion defects were related to skin scores (P < 0.0001), digital ulcers (P = 0.02) and oesophageal involvement (P = 0.046). A trend for anti-Scl 70 antibody positivity was observed in these patients (P = 0.09). Three SPECT-positive patients had re-establishment of normal myocardial perfusion after a course of prostanoid therapy. There were no significant associations between myocardial involvement and age, sex, diffuse/limited SSc, duration of RP or lung involvement. CONCLUSIONS: Myocardial perfusion defects in SSc patients are frequent, and the presence of severe skin thickness, digital ulcers and perhaps oesophageal involvement might warrant screening for myocardial involvement. Further studies are necessary to evaluate the effect of prostanoid therapy on myocardial perfusion.

Interstitial lung disease in systemic sclerosis.

Interstitial lung disease is an early and serious complication of systemic sclerosis (SSc). Because it may be asymptomatic for a long period, and only the early flogistic phase is at present susceptible to treatment, early diagnosis and identification of risk are critical to the outcome. However, identifying SSc patients at risk for developing interstitial lung disease is at present difficult; therefore, a strict monitoring of the disease, especially in the first years, is mandatory. Treatment strategy is aimed at suppressing inflammation. Unfortunately, optimal therapy has not yet been established. Combination of corticosteroids and cyclophosphamide is considered the best therapeutic approach available so far, but doses and duration of treatment need to be determined. Future research should focus on new anti-inflammatory or immunosuppressive agents.

[Pulmonary hypertension in autoimmune rheumatic diseases]. / L'ipertensione polmonare nelle malattie reumatiche autoimmuni.

OBJECTIVE: Pulmonary hypertension is a severe and rapidly progressive disease, particularly frequent in patients with rheumatic diseases. The aims of this study were the following: to determine the prevalence of pulmonary hypertension in Italian patients with autoimmune rheumatic diseases, and to evaluate if the presence of a rheumatic disease in general, or of a specific autoimmune rheumatic disease, is a risk factor for the development of pulmonary hypertension. PATIENTS AND METHODS: One hundred and thirteen Italian patients with connective tissue diseases (105 females, 8 males), aged 19 to 83 yrs, entered the study. Fifty-one had systemic sclerosis (SSc): 49 were females, 2 males, aged 34 to 83 yrs; 41 had limited cutaneous SSc, 8 diffuse cutaneous SSc, and 2 SSc sine scleroderma. Thirty-three patients had systemic lupus erythematosus (SLE): all but one were females, their age ranged from 19 to 82 yrs. Twenty-five had rheumatoid arthritis (RA): 21 females, 4 males, aged 26 to 45 yrs. Three females and one male, 51-77 yrs, had mixed connective tissue disease (MCTD). Systolic pulmonary arterial pressure (SPAP) was assessed by Doppler echocardiography. RESULTS: Twenty three patients had pulmonary hypertension, which was more frequent in MCTD than in SLE (75% vs 6.1%, p=0.0002) or in AR (20%, p=0.0313). Pulmonary hypertension was more frequent in SSc than in SLE (25.5% vs 6.1%, p=0.0028) and in limited than in diffuse SSc (21.6% vs 3.9%). SPAP was significantly related to age (r=0.35, p=0.0275), with patients with pulmonary hypertension older than patients with normal SPAP (66+/-13 vs 52+/-16 yrs, p=0.0003). CONCLUSIONS: These data show a significant association between pulmonary hypertension and autoimmune rheumatic diseases. Therefore, pulmonary hypertension assessment seems mandatory, at least in MCTD and SSc. However, more studies are needed to clarify the relationship between age and pulmonary hypertension and to verify whether the low prevalence of pulmonary hypertension we found in our SLE patients is related or not to their lower age.

Scleroderma heart disease.

Heart disease is a frequent and often severe feature of systemic sclerosis (scleroderma). Cardiomyopathy, with ventricular diastolic dysfunction and arrhythmias, is the most important form, since it is associated with a very poor prognosis. The current challenge is to define its pattern and identify individuals at risk, but evaluation in vivo may be hard to perform. The aim of this review is to provide an update on the clinical aspects of scleroderma heart disease and the early pivotal role that coronary microcirculation dysfunction plays in its development. A discussion of the diagnostic tools now available for this frequently asymptomatic condition will be provided. Treatment options will be reviewed, even though no cure for systemic sclerosis exists, and the current therapy of diastolic dysfunction remains unsatisfactory.

Comparison between iloprost and alprostadil in the treatment of Raynaud's phenomenon.

OBJECTIVE: The prostanoids iloprost and alprostadil are widely used to treat ischaemic changes in patients with Raynaud's phenomenon (RP), but the optimal regimen is poorly defined. We evaluated whether there are differences between iloprost and alprostadil, in terms of either clinical efficacy or of laboratory data, with the aim of assisting in the treatment of connective tissue disease (CTD)-associated RP. METHODS: Twenty-one women with CTD-associated RP were given intravenous iloprost (11 patients) or alprostadil (10 patients) cyclically (5 consecutive days, followed by 1 day every 30 days). Clinical efficacy (RP symptoms, skin score, digital ulcers) and circulating levels of von Willebrand factor (VWf), tissue plasminogen activator (tPA), thrombomodulin (TM) and Type III procollagen N-terminal propeptide (PIIINP) were evaluated by enzyme-linked immunoassay at different intervals. RESULTS: The overall benefits of iloprost and alprostadil were similar. RP improved in 45% versus 90% of patients; ulcers in 60% versus 40% of patients (iloprost versus alprostadil). Skin score did not significantly change with either drug. Circulating VWf decreased with either drug (iloprost -6.2%, alprostadil -9.4%), while tPA, TM, and PIIINP remained unchanged. Side effects were only minor and less frequent with alprostadil. CONCLUSION: Iloprost and alprostadil were both of benefit in CTD-associated RP, without significant differences in either clinical efficacy or circulating markers. However, ease of handling and the lower price favours alprostadil.

Rheumatic disorders and primary biliary cirrhosis: an appraisal of 170 Italian patients.

OBJECTIVE: To establish the frequency of connective tissue diseases (CTD) in a cohort of Italian patients with primary biliary cirrhosis (PBC) and to evaluate the availability of a marker for the early identification of the more common associated CTD. METHODS: One hundred and seventy consecutive patients with histologically diagnosed PBC were screened for the presence of a CTD and/or Raynaud's phenomenon (RP). Patients were classified as having a CTD only if they fulfilled standardised criteria. RESULTS: Forty seven patients had a CTD. The most common CTD was systemic sclerosis (SSc), found in 21 patients. RP was present in 54 patients, most of whom (n=39) had an associated CTD. The most prevalent autoantibodies included antinuclear antibodies (ANA) with anticentromere (ACA) and speckled patterns (34 and 33 patients, respectively) and extractable nuclear antigens (ENA, 27 patients). However, while the frequencies of ACA and ENA were significantly higher in patients with an associated CTD (p<0.0001 and p<0.005, respectively), no relationship was found for speckled ANA. ACA was the best predictor of a CTD in patients with PBC (odds ratio (OR) 24.5, 95% CI 5.5 to 108.8), followed by the presence of ENA (OR 23.9, 95% CI 5.6 to 101.0) and RP (OR 20.2, 95% CI 5.7 to 71.2). CONCLUSIONS: Using strict standardised classification criteria we have found that SSc is the most common CTD associated with PBC and that ACA and ENA are strong markers for an associated CTD in patients with PBC.

Homocysteine concentration in primary and systemic sclerosis associated Raynaud's phenomenon.

OBJECTIVE: To investigate whether patients with systemic sclerosis (SSc) have raised homocysteine (Hcy) plasma levels, thought to be an independent risk factor for vascular disease, and to study the relationship between Hcy and endothelial damage, and between Hcy and methylene-tetrahydrofolate reductase (MTHFR) genotypes, and patients' vitamin nutritional status, which are among the more frequent causes of hyperhomocysteinemia. METHODS: We measured Hcy, von Willebrand factor (vWF), folic acid, and vitamin B12 plasma levels and analyzed the frequencies of MTHFR mutations in 30 patients with SSc and 12 patients with primary Raynaud's phenomenon (RP); 29 healthy subjects served as controls. RESULTS: Patients with SSc had higher Hcy and vWF concentrations than those with RP (p < 0.01 and p < 0.02, respectively) or controls (p < 0.02 and p < 0.0001, respectively). Folic acid and vitamin B12 were lower in SSc than in RP (p < 0.01 and p < 0.02, respectively) or controls (p < 0.05). MTHFR genotype did not influence Hcy, folate, or vitamin B12 concentrations, but patients homozygous for the mutant gene had higher vWF levels. CONCLUSION: Patients with SSc, but not those with RP, had significantly higher Hcy and vWF plasma levels. Nutritional rather than inherited factors seem to have a pathogenic role in SSc hyperhomocysteinemia.