Human parvovirus B19: a review of clinical and epidemiological aspects in Brazil.

Since the first evidence of human parvovirus B19 (B19V) infection in late 80s, several studies have been conducted to clarify the spectrum of clinical diseases in Brazil. B19V infection is prevalent in the general population and has exhibited a cyclical pattern of occurrence every 4-5 years, with the predominance of genotype 1 over 3b. During epidemic periods the wide range of clinical conditions, such as ertythema infectiosum, arthropathy, transient aplastic crisis, nonimmune hydrops fetalis and B19V-hepatitis were diagnosed. However, many infections are likely asymptomatic or have a self-limiting clinical course and are not readly diagnosed. Besides, the similarity of the symptoms of ertythema infectiosum to other rash diseases and the broadly circulation of arboviruses makes differential diagnosis more difficult. In this article, we provide a historical comprehensive overview of the research on parvovirus B19 conducted in Brazil, with a focus on the clinical and epidemiological aspects of the infection.

Osteoarticular manifestations of Mayaro virus infection.

PURPOSE OF REVIEW: To carry out an update on the state of the art of the Mayaro virus (MAYV) infection and its osteoarticular implications. RECENT FINDINGS: There is a wide distribution of MAYV in Latin America and documented exported cases to the United States and Europe. Although osteoarticular involvement is not the most frequent, it is one the most associated with disability. The main mechanisms related to arthropathy involves cellular infiltrates (i.e. macrophages, natural killer cells, lymphocytes) together with production of cytokines, such as IL-6, IL-7, IL8, IL-12p70. SUMMARY: MAYV infection is an emerging disease, which has been reported in many and increasing number of countries of Latin America. There is a high risk of epidemic outbreaks, given the inadequate vector control (Aedes mosquitoes). Its main symptoms, like other arbovirus infections, involve the presence of headache, rash, conjunctivitis, and arthralgias. MAYV arthropathy is usually severe, can last in time, and is associated with severe disability. There is currently no treatment for MAYV. Prevention of MAYV as a public health burden will be achieved by integrating vector control with vaccines (still under development).

Alfavirus tropicales artritogénicos / Tropical arthritogenic alphaviruses

Los alfavirus tropicales tienen especial tropismo por el tejido osteoarticular. Los pacientes desarrollan cuadros crónicos reumatológicos similares a la artritis reumatoide y la espondilitis anquilosante. El prototipo es el virus Chikungunya, aunque otros virus menos conocidos en nuestro medio como Sindbis, Ross River, Mayaro, O’nyong nyong y Barmah Forest tienen un potencial para propagarse a través de vectores y causar cuadros reumatológicos crónicos. Los movimientos poblacionales internacionales han aumentado el número de pacientes diagnosticados por estos virus tropicales en zonas no endémicas. Dado que pueden dejar secuelas y afectar la calidad de vida, es importante conocerlos. Los cambios en los ecosistemas han favorecido la expansión de mosquitos competentes, haciendo realidad el temor de transmisión local en el sur de Europa. El objetivo de esta revisión es dar una aproximación clínica de los distintos alfavirus tropicales artritogénicos, especialmente de aquellos en los que la patología reumática crónica es más frecuente (AU)

Tropical alphaviruses have special tropism for bone and joint tissue. Patients can develop chronic rheumatic disorders similar to rheumatoid arthritis and ankylosing spondylitis. The prototype is Chikungunya virus, although other lesser known viruses in our environment such as Sindbis, Ross River, Mayaro, O’nyong nyong and Barmah Forest viruses have the potential to be sped through vectors and cause chronic rheumatic disease. International population movements have increased the numbers of patients diagnosed with these tropical viruses in areas in which they are not endemic. Since they can leave persistent symptoms and affect the quality of life of the patients, it is important that we be aware of them. Changes in ecosystems have favored the expansion of competent mosquitoes, making fears of local transmission in southern Europe a reality. The objective of this review is to provide a clinical approach to the different arthritogenic tropical alphaviruses, especially those in which chronic rheumatic disease is more frequent (AU)

Development & standardization of an in-house IgM indirect ELISA for the detection of parvovirus B19 infections.

BACKGROUND & OBJECTIVES: Parvovirus B19 infections occur worldwide; the infection is acquired early in childhood but could occur later. B19 is reported to cause infection in childhood febrile illnesses, and arthropathies in adults and children and in end-stage renal disease (ESRD) seen in adults. This study was designed to develop an in-house IgM indirect ELISA for serological screening among patients and controls, and to compare ELISA results with those of nested polymerase chain reaction (nPCR) assay. METHODS: An in-house IgM indirect ELISA was standardized using peptide sequence of VP1/VP2 region of parvovirus B19. A total of 201 children and adult with febrile illnesses, 216 individuals with non-traumatic arthropathies, 201 cases of chronic anaemia associated with ESRD and 100 healthy controls were tested. Serum was separated from the blood and subsequently used for DNA extraction. The nested polymerase chain reaction (nPCR) for the detection of B19V DNA was performed using primers targeting the overlapping region of VP1/VP2 capsid protein genes. RESULTS: A total of 618 samples were tested for parvovirus B19 by an in-house IgM indirect ELISA. Among these samples, six were positive by in-house ELISA. The inter-rater agreement between ELISA and PCR assays was calculated using kappa coefficient analysis. The value of κ was 0.77 and the strength of agreement was 'good' (P<0.001). INTERPRETATION & CONCLUSIONS: The in-house IgM indirect ELISA was found to be simple with high sensitivity and specificity when compared with nPCR and could be used as an alternative to expensive commercial kits in resource-poor settings.

Pentosan Polysulfate: a Novel Glycosaminoglycan-Like Molecule for Effective Treatment of Alphavirus-Induced Cartilage Destruction and Inflammatory Disease.

UNLABELLED: Arthritogenic alphaviruses such as Ross River virus (RRV) and chikungunya virus (CHIKV) cause large-scale epidemics of severe musculoskeletal disease and have been progressively expanding their global distribution. Since its introduction in July 2014, CHIKV now circulates in the United States. The hallmark of alphavirus disease is crippling pain and inflammation of the joints, a similar immunopathology to rheumatoid arthritis. The use of glycans as novel therapeutics is an area of research that has increased in recent years. Here, we describe the promising therapeutic potential of the glycosaminoglycan (GAG)-like molecule pentosan polysulfate (PPS) to alleviate virus-induced arthritis. Mouse models of RRV and CHIKV disease were used to characterize the extent of cartilage damage in infection and investigate the potential of PPS to treat disease. This was assessed using histological analysis, real-time PCR, and fluorescence-activated cell sorting (FACS). Alphaviral infection resulted in cartilage destruction, the severity of which was alleviated by PPS therapy during RRV and CHIKV clinical disease. The reduction in cartilage damage corresponded with a significant reduction in immune infiltrates. Using multiplex bead arrays, PPS treatment was found to have significantly increased the anti-inflammatory cytokine interleukin-10 and reduced proinflammatory cytokines, typically correlated with disease severity. Furthermore, we reveal that the severe RRV-induced joint pathology, including thinning of articular cartilage and loss of proteoglycans in the cartilage matrix, was diminished with treatment. PPS is a promising new therapy for alphavirus-induced arthritis, acting to preserve the cartilage matrix, which is damaged during alphavirus infection. Overall, the data demonstrate the potential of glycotherapeutics as a new class of treatment for infectious arthritis. IMPORTANCE: The hallmark of alphavirus disease is crippling pain and joint arthritis, which often has an extended duration. In the past year, CHIKV has expanded into the Americas, with approximately 1 million cases reported to date, whereas RRV continues to circulate in the South Pacific. Currently, there is no licensed specific treatment for alphavirus disease, and the increasing spread of infection highlights an urgent need for therapeutic intervention strategies. Pentosan polysulfate (PPS) is a glycan derivative that is orally bioavailable, has few toxic side effects, and is currently licensed under the name Elmiron for the treatment of cystitis in the United States. Our findings show that RRV infection damages the articular cartilage, including a loss of proteoglycans within the joint. Furthermore, treatment with PPS reduced the severity of both RRV- and CHIKV-induced musculoskeletal disease, including a reduction in inflammation and joint swelling, suggesting that PPS is a promising candidate for drug repurposing for the treatment of alphavirus-induced arthritis.

The duration of gastrointestinal and joint symptoms after a large waterborne outbreak of gastroenteritis in Finland in 2007--a questionnaire-based 15-month follow-up study.

An extensive drinking water-associated gastroenteritis outbreak took place in the town of Nokia in Southern Finland in 2007. 53% of the exposed came down with gastroenteritis and 7% had arthritis-like symptoms (joint swelling, redness, warmth or pain in movement) according to a population-based questionnaire study at 8 weeks after the incident. Campylobacter and norovirus were the main pathogens. A follow-up questionnaire study was carried out 15 months after the outbreak to evaluate the duration of gastrointestinal and joint symptoms. 323 residents of the original contaminated area were included. The response rate was 53%. Participants were inquired about having gastroenteritis during the outbreak and the duration of symptoms. Of those with gastroenteritis, 43% reported loose stools and abdominal pain or distension after the acute disease. The prevalence of symptoms declined promptly during the first 3 months but at 15 months, 11% reported continuing symptoms. 32% of the respondents with gastroenteritis reported subsequent arthritis-like symptoms. The disappearance of arthritis-like symptoms was more gradual and they levelled off only after 5 months. 19% showed symptoms at 15 months. Prolonged gastrointestinal symptoms correlated to prolonged arthritis-like symptoms. High proportion of respondents continued to have arthritis-like symptoms at 15 months after the epidemic. The gastrointestinal symptoms, instead, had declined to a low level.

The association between hepatitis B virus infection and disease activity, synovitis, or joint destruction in rheumatoid arthritis.

The prevalence of chronic hepatitis B virus (HBV) infection in China is high. Four percent of patients with HBV infection can present with polyarthritis and positive rheumatic factor similar to rheumatoid arthritis (RA). Here, we investigated the association between HBV infection and serological, radiological, or histological disease status in RA. According to HBV infection status, 223 consecutive hospitalized Chinese patients with RA were divided into the groups of chronic HBV infection, past HBV infection, and no HBV infection. Clinical data and hand radiographs were collected. Synovium was obtained by closed-needle biopsy, and serial tissue sections were stained immunohistochemically for HBV surface antigen (HBsAg) and cluster of differentiation (CD) markers. (1) The prevalence of HBsAg positivity and chronic hepatitis B in RA was consistent with the age-matched general Chinese population (11.2 vs. 8.7 %, 1.7 vs. 1.0 %, respectively, P > 0.05). (2) Clinical parameters, disease activity score in 28 joints, or Sharp scores showed no significant difference among the three groups in 206 RA or 140 treatment-naïve patients, both with active disease (all P > 0.05). (3) Synovial immunohistochemical staining showed negative HBsAg in ten RA patients with HBV carrier status and ten RA patients with past HBV infection. Except for higher subintimal CD3+ cell density in the past HBV infection group, Krenn's synovitis score, mean densities of subintima positive-staining cells (CD20, CD38, CD79a, and CD68), and CD34+ microvessel counts showed no significant difference among RA patients with HBV carrier status, past HBV infection, or no HBV infection (all P > 0.05). Chronic HBV infection may have no significant effect on disease activity, synovitis, or joint destruction in RA.

Antibodies to mutated citrullinated vimentin in patients with chronic hepatitis C virus genotype IV infection-related arthropathy.

One of the extra-hepatic manifestations of hepatitis C virus (HCV) infection is polyarthritis that mimics rheumatoid arthritis (RA). Anti-mutated citrullinated vimentin (MCV) was recently introduced in the diagnostic workup of RA, but its exact role in HCV infection and its related arthropathy is still unclear. The aim of the study is to determine the prevalence of anti-MCV antibodies in HCV-infected patients with or without articular involvement, and to investigate whether anti-MCV antibodies have an additional role to anticyclic citrullinated peptide (CCP) antibodies and rheumatoid factor (RF) in differentiating patients with RA from patients with HCV-related arthropathy. Fifty-five HCV-infected patients (HCV RNA positive) and 30 RA patients (fulfilling the American College of Rheumatology classification criteria for RA and negative for HCV) were included. Anti-MCV antibodies, anti-CCP antibodies, RF and cryoglobulins were measured. Articular involvement in hepatitis C patients was evaluated. Articular involvement was detected in 30/55 (54.5%) of HCV-infected patients. The most frequent pattern was symmetric polyarthralgias and the most frequent joints to be involved were the wrists, metacarpophalangeal joints, shoulders and knees. In HCV arthropathy, anti-MCV was positive in 9/30 (30%), anti-CCP in 0% and RF in 22/30 (73.3%). Whereas, in chronic HCV without arthropathy, anti-MCV was positive in 8 patients (32%), anti-CCP in one patient (4%) and RF in 23/25 (92.0%). There was no significant difference between the two HCV groups as regards the frequencies of anti-MCV (P = 0.89), anti-CCP (P = 0.93) and RF (P = 0.15). In RA, anti-MCV was positive in 93.3% anti-CCP in 96.7% and RF in 86.7%. There was no significant difference in RF between RA and HCV arthropathy (P = 0.33). Meanwhile, there was a highly significant difference between both groups regarding anti-MCV and anti-CCP (P < 0.0001 for each). The sensitivity of anti-MCV, anti-CCP and RF for RA was 93.3, 96.7 and 86.7%, respectively. Whereas their specificity was 69.1, 98.2 and 18.2%, respectively. In addition, the mean levels of anti-MCV and anti-CCP were significantly increased in RA than in all HCV patients (P = 0.038 and P < 0.0001, respectively). Meanwhile, there were no significant differences in mean levels of anti-MCV and anti-CCP between HCV patients with arthropathy and those without arthropathy (P = 0.11 and P = 0.73, respectively). Also, there were no differences in mean RF between both HCV groups. There was a significant positive correlation between anti-MCV and anti-CCP levels in patients with HCV-related arthropathy (r = 0.39, P = 0.032) and in those without arthropathy (r = 0.578, P = 0.002). Cryoglobulins were detected in 7/30 HCV-related arthropathy (23.3%) and were positively correlated with anti-MCV(r = 0.485, P = 0.007). Anti-CCP still attains the major role in differentiating RA from HCV arthropathy. Anti-MCV seems to play no additional role in this aspect. The role of mutation of vimentin in the pathogenesis of HCV arthropathy is not as clear as it is for RA and needs further investigation.

Transient synovitis of the hip: more evidence for a viral aetiology.

OBJECTIVES: Transient synovitis (TS) of the hip is a common cause of limping in children. A link with infection has been suggested but has not been firmly established. We conducted a case-control study to determine whether the TS is associated with infection. METHODS: We enrolled children diagnosed with TS in our emergency department over a 10-week period. For each case, we identified an age-matched and sex-matched child with a fracture. Parents of cases and controls were questioned with regard to recent infectious illness in their child according to a predefined questionnaire. RESULTS: A paired analysis showed that children with TS (N=29) were more likely to have experienced recent infection with vomiting or diarrhoea (P=0.004) and 'common cold symptoms/runny nose' (P=0.006) than the children with fractures (N=29). Other symptoms suggestive of either viral or bacterial infection were not significantly associated with TS. CONCLUSION: TS is associated with symptoms of gastroenteritis and the common cold.

Prevalence and characteristics of articular manifestations in human immunodeficiency virus infection.

BACKGROUND: Articular manifestations have been reported in HIV infection with a prevalence ranging from 2.5 to 68%. OBJECTIVES: To determine the prevalence, types and characteristics of articular manifestations in the anti-retroviral treatment naive HIV infected patients. DESIGN: Cross sectional descriptive study. SETTING: Comprehensive care clinic (HIV outpatient clinic) at the Kenyatta National Hospital (KNH) from October 2007 to March 2008. SUBJECTS: One hundread and ninety three patients; 135 females and 58 males, aged between 19 to 65 years with Human immunodeficiency virus (HIV) infection who were naive to anti - retroviral drug therapy. MAIN OUTCOME MEASURE: Presence of articular manifestations that included HIV associated arthritis, HIV associated spondyloarthropathies, HIV associated arthralgia, painful articular syndrome and avascular necrosis. RESULTS: Thirty three of these 193 patients had articular manifestation with a prevalence of 17.1%. The type prevalence was; HIV associated arthralgia, 15.6%; undifferentiated spondyloarthropathy, 1% and HIV associated arthritis; 0.5%. Their mean age was 36 +/- 9 years, range 23-63 years; majority were female, male to female ratio of 1: 2.3 and the majority were in World health organization (WHO) clinical staging of HIV infection, class II and III with a mean CD4 cell count of 330 cells/mm3. Seventeen (51.5%) of the patients with articular disease had oligo - articular presentation, 10(30.3%) mono - articular while 6(18.2%) had poly - articular presentation. The mean duration of joint pains was 53.3 days (range of 2-365 days). Six (18.2%) of these 33 patients missed work, home making activities or school due to the articular disease. CONCLUSION: Articular manifestations are common in HIV infection with a prevalence of 17.1%. HIV associated arthralgia was the most common manifestation. Majority of these patients were female, male to female ratio of 1: 2.3. The mean age of these patients was 36 years with a mean CD4 cell count of 330 cells/mm3 with 18.2% of them missing school or work.

Acute arthropathy in patients with rash diseases: a comparative study.

The aim of this study was to assess the association of acute arthropathy and selected clinical features in patients with acute rash diseases. Serum samples from 1,554 patients were tested for anti-measles, dengue, human parvovirus B19, and rubella virus IgM using enzyme immunoassay. Sera from children, in whom these infections were excluded, were studied for anti-human herpesvirus type 6 IgG antibodies using an indirect immunofluorescence test. Joint complaints occurred in 31.2% of the 862 patients with an etiologic diagnosis and were more frequently seen in adults than in children (OR 8.5). Among the adults, arthropathy prevailed in women compared to men (OR 1.8). Arthropathy was most frequently reported in rubella (41.2%) and in dengue fever cases (41.1%) than in the other rash diseases studied (p < 0.0001). Joint complaints were more frequently seen in patients with fever (OR 1.6) and with five or more days of onset of the disease (OR 1.6), regardless of serological diagnosis. Arthropathy appeared as a frequent condition in rash diseases, typically with low severity and no specific pattern of joint involvement.

Anti-cyclic citrullinated peptide antibodies distinguish hepatitis B virus (HBV)-associated arthropathy from concomitant rheumatoid arthritis in patients with chronic HBV infection.

OBJECTIVE: To determine whether anti-cyclic citrullinated peptide (anti-CCP) antibodies, which are a highly specific test for rheumatoid arthritis (RA), could differentiate between hepatitis B virus (HBV)-associated arthropathy and concomitant RA in Korean patients with chronic HBV infection. METHODS: We investigated 240 patients with HBV infection. Anti-CCP antibodies were measured by ELISA and rheumatoid factor (RF) by the latex fixation test. Patient records were reviewed, and a standard form was used to record all demographic, clinical, and laboratory characteristics. Patients were divided into 4 groups according to joint symptoms: asymptomatic, arthralgia, oligoarthritis, and RA. We categorized liver disease into 3 groups: carrier, chronic hepatitis, and cirrhosis. RESULTS: Anti-CCP antibodies and RF were detected in 11 and 28 of 240 patients, respectively. Anti-CCP antibodies were detected in 9 of 10 RA (90%) and 2 of 230 non-RA patients (0.86%). The positive rate for RF was 90% in RA and 8.3% in non-RA. Eight of 10 RA patients were positive for both RF and anti-CCP antibodies. RF was detected in 11 patients without joint symptoms, 4 with arthralgia, and 4 with oligoarthritis, whereas anti-CCP antibodies were found in 1 patient without joint symptoms and 1 with oligoarthritis. Specificity of anti-CCP antibody for RA was 99.1%, whereas RF showed 91.7% specificity (p<0.0002). We compared the titers and positive detection rates of anti-CCP antibodies and RF among liver disease subgroups. There was no significant between-subgroup difference. CONCLUSION: Measurement of anti-CCP antibodies is better than RF detection to discriminate HBV-associated arthropathy from concomitant RA in patients with chronic HBV infection.

Experimental modeling of viral diseases of the locomotor system.

Dissemination of infectious inflammation was studied in experimental influenza and acute and chronic herpesvirus infections. The possibility of articular involvement into the infectious process was evaluated. Pathomorphological signs of changes in the articular tissue confirmed the effects of these viruses on the locomotor pathology. Results of virus infection simulation in experimental animals suggest this model for studies of the pathogenesis of diseases of viral etiology (including those with articular involvement) in humans.

Historia natural y manifestaciones clínicas de la hepatitis B crónica / Natural history and clinical manifestations of chronic hepatitis B virus

La infección por virus de la hepatitis B (VHB) representa un importante problema de salud pública en todo el mundo. En las últimas décadas se han producido importantes progresos que han contribuido a una mayor comprensión de la historia natural y las manifestaciones clínicas de esta infección. La fluctuación entre la replicación viral y la respuesta inmunológica del huésped tiene implicaciones en la patogenia y la evolución de la lesión hepática. En el adulto inmunocompetente, la mayor parte de infecciones por VHB se resuelven de forma espontánea, en comparación con una evolución hacia una infección crónica en la mayoría de los recién nacidos. Los pacientes con hepatitis crónica por VHB o hepatitis B crónica pueden presentarse en cuatro fases evolutivas: a) fase de tolerancia inmunológica o inmunotolerancia; b) hepatitis B crónica HBeAg positivo; c) estado de portador inactivo de HBsAg, y d) hepatitis crónica HBeAg negativo. La hepatitis crónica HBeAg positivo o negativo puede evolucionar hacia una cirrosis, una insuficiencia hepática y un carcinoma hepatocelular. Una progresión hacia estas complicaciones es más frecuente en las formas HBeAg negativo, asociadas con mutaciones que afectan a la región pre-core y que mantienen la replicación viral activa. Los factores de riesgo son unos valores altos de ADN-VHB, el aumento de la concentración sérica de transaminasas y algunos genotipos. Estos factores subrayan la necesidad de evaluar y supervisar a todos los portadores del VHB para identificar a los pacientes que pueden beneficiarse de un tratamiento antiviral precoz, evitando de este modo la progresión hasta formas más avanzadas de hepatopatía. Estas medidas pueden contribuir a una mejor prevención y a un tratamiento más eficaz de la hepatitis B(AU)

Hepatitis B virus (HBV) infection is a serious public health problem worldwide. In the last few decades, major advances have been achieved that have contributed to greater understanding of the natural history and clinical manifestations of this infection. The fluctuation between viral replication and the host¿s immune response has implications in the pathogenesis and progression of the hepatic lesion. In immunocompetent adults, most HBV infections resolve spontaneously in contrast with progression to chronic infection in most infants. Patients with chronic hepatitis due to HBV or chronic hepatitis B can present at four phases: 1) the immune tolerance phase, 2) HBeAg-positive chronic hepatitis B, 3) inactive HBsAg carrier state, and 4) HBeAg-negative chronic hepatitis. HBeAg-positive or ¿negative chronic hepatitis can progress to cirrhosis, liver failure and hepatocellular carcinoma. Progression to these complications is more frequent in HBeAg-negative forms, associated with mutations that affect the pre-core region and maintain active viral replication. Risk factors are HBV-DNA positive serum levels, an increase in serum transaminase levels and some genotypes. These factors highlight the need to evaluate and monitor all HBV carriers to identify those who could benefit from early antiviral treatment, thus avoiding progression to more advanced forms of liver disease. These measures could improve prevention and treatment of hepatitis B(AU)

Etanercept treatment for three months is safe in patients with rheumatological manifestations associated with hepatitis C virus.

OBJECTIVE: The treatment of the rheumatological manifestations associated with hepatitis C virus (HCV) remains difficult. To examine the safety of anti-tumour necrosis factor-alpha treatment, nine patients having rheumatological manifestations associated with HCV were treated with etanercept 25 mg twice a week for 3 months. METHODS: Five patients had a positive viral load at study entry (Group I), four were negative (Group II). Clinical data recorded were: disease duration, painful and swollen joint count, patient global and physician global assessment, the number of 18 specified fibromyalgia tender points and the Health Assessment Questionnaire score. Laboratory studies included checking for the presence of cryoglobulinaemia and transaminase levels. Quantitative HCV viral RNA was performed by real-time polymerase chain reaction (PCR). RESULTS: At 3 months, no patient was found to have evidence of increased hepatic inflammation based on serial serum transaminase levels. In the five patients from Group I with detectable HCV RNA, no significant viral load increase was observed. No reactivation was observed in the four patients from Group II with undetectable HCV RNA. The effect on the clinical rheumatological manifestations was more heterogeneous but appears to be lower than that observed in rheumatoid arthritis. CONCLUSION: In this phase II open short-term study, etanercept appeared to be safe in patients with articular manifestations associated with HCV.

Soft tissue rheumatic lesions and HIV infection in Zambians.

OBJECTIVE: To explore the relationship between human immunodeficiency virus (HIV) infection and soft tissue rheumatic lesions in HIV-positive black Zambians. METHODS: We performed a prospective study of all patients over 18 years of age attending a rheumatic clinic in a teaching hospital. All patients underwent routine blood tests, and radiographs were performed when indicated. HIV status was determined by ELISA, and clinical staging was determined by World Health Organization criteria. Patients with isolated sacroiliac pain, enthesitis, or a soft tissue lesion were selected for analysis. For HIV-positive patients, only those in clinical stage 1 (asymptomatic or persistent generalized lymphadenopathy) were selected. RESULTS: Our study cohort comprised 120 patients (41 men, 79 women, age 23-70 yrs). Diagnosis and number (% HIV positive) were distributed as follows: sacroiliitis, 14 (100%); heel pain, 14 (100%); costochondritis, 3 (100%); polyenthesitis (> or = 4 sites), 20 (100%); carpal tunnel syndrome, 8 (63%); rotator cuff syndrome, 18 (30%); tendinitis, 8 (25%); sciatica/cervical spondylosis, 12 (16%); sacroiliac strain, 7 (0%); and de Quervain's tenosynovitis, 16 (0%). HIV seroprevalence was 54% overall, 74% in those under 45 years of age, and 17% in those over 45 years of age. Population prevalence of HIV in Lusaka is about 30% in the 30-40-year age range. Mean erythrocyte sedimentation rate (ESR) in 65 patients positive for HIV was 80 mm/h and in 55 patients negative for HIV, 18 mm/h. Within each subgroup the mean ESR was significantly higher in HIV-positive patients. CONCLUSION: A young age and a raised ESR are both good indications of HIV infection in Zambian patients with soft tissue lesions. Enthesitis is a distinct HIV-related phenomenon, either an early form or a forme fruste of HIV-related spondyloarthropathy.

Clinical aspects of parvovirus B19 infection.

Parvovirus B19 is a significant human pathogen that causes a wide spectrum of clinical complications ranging from mild, self-limiting erythema infectiosum in immunocompetent children to lethal cytopenias in immunocompromised patients and intrauterine foetal death in primary infected pregnant women. The infection may also be persistent and can mimic or trigger autoimmune inflammatory disorders. Another important clinical aspect to consider is the risk of infection through B19-contaminated blood products. Recent advances in diagnosis and pathogenesis, new insights in the cellular immune response and newly discovered genotypes of human parvoviruses form a platform for the development of modern therapeutic and prophylactic alternatives.

Clinical and laboratory manifestations of Sindbis virus infection: prospective study, Finland, 2002-2003.

Sindbis virus (SINV) is widespread in Europe, Africa, Australia, and Asia, but clinical infection occurs as epidemics in a few geographically restricted areas. We recently proved, by virus isolation from patients, that SINV is the causative agent of Pogosta disease, a mosquito-borne rash-arthritis occurring as larger epidemics every seventh year in Finland. Altogether, 86 patients with serologically verified SINV infection were recruited to the present study during the 2002 outbreak. We now describe in detail the duration, incidence, and characteristics of different symptoms; hematological parameters; antibody kinetics; and presence of SINV in different tissue samples. SINV RNA detection or virus isolation from blood and/or skin lesions was successful in 8 patients. Immunoglobulin (Ig) M antibodies became detectable within the first 8 days of illness, and IgG antibodies became detectable within the first 11 days of illness. During the acute phase of Pogosta disease, the typical symptoms were arthritis, itching rash, fatigue, mild fever, headache, and muscle pain. The most notable finding was that, in 50% of the patients, joint symptoms lasted for >12 months.

Role of anti-cyclic citrullinated peptide antibodies in discriminating patients with rheumatoid arthritis from patients with chronic hepatitis C infection-associated polyarticular involvement.

This study was performed to assess the utility of anti-cyclic citrullinated peptide (anti-CCP) antibodies in distinguishing between patients with rheumatoid arthritis (RA) and patients with polyarticular involvement associated with chronic hepatitis C virus (HCV) infection. Serum anti-CCP antibodies and rheumatoid factor (RF) were evaluated in 30 patients with RA, 8 patients with chronic HCV infection and associated articular involvement and 31 patients with chronic HCV infection without any joint involvement. In addition, we retrospectively analysed sera collected at the time of first visit in 10 patients originally presenting with symmetric polyarthritis and HCV and subsequently developing well-established RA. Anti-CCP antibodies and RF were detected by commercial second-generation anti-CCP2 enzyme-linked immunosorbent assay and immunonephelometry respectively. Anti-CCP antibodies were detected in 23 of 30 (76.6%) patients with RA but not in patients with chronic HCV infection irrespective of the presence of articular involvement. Conversely, RF was detected in 27 of 30 (90%) patients with RA, 3 of 8 (37.5%) patients with HCV-related arthropathy and 3 of 31 (9.7%) patients with HCV infection without joint involvement. Finally, anti-CCP antibodies were retrospectively detected in 6 of 10 (60%) patients with RA and HCV. This indicates that anti-CCP antibodies can be useful in discriminating patients with RA from patients with HCV-associated arthropathy.

Persistence of human parvovirus B19 in human tissues.

Human parvovirus B19 infection causes various clinical symptoms, such as rash, arthropathy, anemias and fetal death, but it can also remain asymptomatic. The arthropathies and anemias can become chronic for several years, not infrequently resembling autoimmune syndromes. B19 replicates only in red blood cell precursors of bone marrow or fetal liver, resulting in high-titred short-lived viremia, but viral DNA is detectable also in cells of several other types. Recently B19 DNA has been found, by very sensitive amplification tests, in certain tissues not only of symptomatic but also of healthy individuals for several years or decades after B19 infection. The mere presence of B19 DNA in these tissues of a symptomatic patient (e.g. joints in chronic arthritis or skin in dermatomyositis) thereby does not prove that the present disease is caused by B19. The diagnosis has to be verified by other innovative means. How and why viral DNA persists in the tissues of healthy individuals is under investigation.