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1.  Hepatitis A with Pleural Effusion, Ascites and Acalculous Cholecystitis 
Iranian Journal of Pediatrics  2010;20(4):479-482.
Hepatitis A virus (HAV) infection constitutes an important health problem in developing countries. It is usually a benign self-limiting disease, but may present with atypical clinical findings.
Case Presentation
A twelve-year-old male with ascites, pleural effusion, and acalculous cholecystitis during the course of HAV infection is reported. He was managed conservatively and clinical improvement was observed with resolution of HAV infection.
To our knowledge, this is the first case in which all these three rare complications were observed in a single patient in the early period of disease.
PMCID: PMC3446093  PMID: 23056750
Pleural effusion; Ascites; Acalculous cholecystitis; Hepatitis A virus; Hepatitis
2.  Acute hepatitis a virus infection presenting with multiorgan dysfunction: a case report 
Cases Journal  2009;2:8124.
Acute hepatitis due to hepatitis a virus is usually a benign self-limiting disease conferring lifelong immunity. However, few cases have been reported in literature with fulminant hepatitis. We report this extremely rare case with multiorgan dysfunction including liver failure, hepatic encephalopathy, renal failure, pleural effusion, pericardial effusion and hematologic dysfunction as a sequale of this infection in an otherwise healthy male at the age of 18.
Case presentation
An 18 years old Pakistani male presented with two days history of fever, cough, headache and vomiting. His condition gradually deteriorated and on day 7 developed multiorgan dysfunction. Initially Immunoglobulin M anti hepatitis a virus was borderline 1.40 but repeated titers one week later confirmed the diagnosis of acute hepatitis a virus infection.
This original case report highlights the importance of focusing first uncommon manifestations of common illnesses while diagnosing difficult cases. Moreover this case also adds knowledge to the limited available data regarding complications and predictors of prognosis.
PMCID: PMC2740024  PMID: 19830052
3.  Hepatitis A vaccine should receive priority in National Immunization Schedule in India 
Human Vaccines & Immunotherapeutics  2012;8(8):1132-1134.
Hepatitis A is an acute, usually self-limiting infection of the liver caused by a virus known as hepatitis A virus (HAV). Humans are the only reservoir of the virus; transmission occurs primarily through the fecal-oral route and is closely associated with poor sanitary conditions. The virus has a worldwide distribution and causes about 1.5 million cases of clinical hepatitis each year. The risk of developing symptomatic illness following HAV infection is directly correlated with age. As many 85% of children below 2 y and 50% of those between 2–5 y infected with HAV are anicteric, and among older children and adults, infection usually causes clinical disease, with jaundice occurring in more than 70% of cases. The infection is usually self-limiting with occasional fulminant hepatic failure and mortality. In most developing countries in Asia and Africa, hepatitis A is highly endemic such that a large proportion of the population acquires immunity through asymptomatic infection early in life. HAV is endemic in India; most of the population is infected asymptomatically in early childhood with life-long immunity. Several outbreaks of hepatitis A in various parts of India have been recorded in the past decade such that anti-HAV positivity varied from 26 to 85%. Almost 50% of children of ages 1–5 y were found to be susceptible to HAV. Any one of the licensed vaccines may be used since all have nearly similar efficacy and safety profiles (except for post-exposure prophylaxis / immunocompromised patients, where only inactivated vaccines may be used). Two doses 6 mo apart are recommended for all vaccines. All Hepatitis A vaccines are licensed for use in children aged 1 y or older. However in the Indian scenario, it is preferable to administer the vaccines at age 18 mo or more when maternal antibodies have completely declined. Vaccination at this age is preferable to later since it is easier to integrate with the existing schedule, protects those who have no antibodies, and protects children by the time they attend day care. In India the vaccine against hepatitis A is available for the people who can afford it, but the government of India should give this vaccine as a priority in the national immunization schedule.
PMCID: PMC3551887  PMID: 22854671
hepatitis A virus; immunity; jaundice; outbreak; vaccines
4.  Symptomatic Isolated Pleural Effusion as an Atypical Presentation of Ovarian Hyperstimulation Syndrome 
Ovarian hyperstimulation syndrome (OHSS) presents in ~33% of ovarian stimulation cycles with clinical manifestations varying from mild to severe. Its pathogenesis is unknown. Pleural effusion is reported in ~10% of severe OHSS cases and is usually associated with marked ascites. The isolated finding of pleural effusions without ascites, as the main presenting symptom of OHSS is not frequently reported and its pathogenesis is also unknown. We describe two unusual cases of OHSS where dyspnea secondary to unilateral pleural effusion was the only presenting symptom. By reporting our experience, we would like to heighten physicians' awareness in detecting these cases early, as it is our belief that the incidence of pleural effusion in the absence of most commonly recognized risk factors for OHSS may be underestimated and may significantly compromise the health of the patient if treatment is not initiated in a reasonable amount of time.
PMCID: PMC3335556  PMID: 22567522
5.  Benign asbestos pleural effusion: diagnosis and course. 
Thorax  1981;36(12):896-900.
We have reviewed 22 patients with benign asbestos pleural effusion seen over a 17-year period. The mean duration of exposure to asbestos was 5.5 years and the mean interval between exposure and presentation was 16.3 years. In five the effusion was asymptomatic. Fever was uncommon but in 15 of 21 patients the ESR was elevated. Leucocytosis was noted in seven of 20 patients. Autoantibodies were rarely detected. The pleural fluid was usually blood-stained and the volume aspirated was rarely larger than 500 ml. Pleural biopsies revealed established pleural fibrosis and/or inflammatory infiltration with fibrinous exudate and mesothelial and fibroblastic proliferation. A positive mantoux test was noted in eight of 12 patients but there was no other evidence of tuberculosis. The mean duration to spontaneous resolution of the effusion was 4.3 months. During a follow-up period of 28.1 years from initial exposure to asbestos (mean 22.8 years) and up to 17.2 years from initial presentation with a pleural effusion (mean 6.3 years) seven patients had a single recurrence and only one patient had multiple pleural effusions. Only three patients experienced persistent pleural pain. It was not possible to predict the likelihood of recurrence of an effusion or the persistence of pleural pain from the data at presentation. No patient subsequently developed mesothelioma or other neoplasm.
PMCID: PMC471853  PMID: 7336367
6.  Massive pleural effusions in cryptococcal meningitis 
Postgraduate Medical Journal  1999;75(883):297-298.
Cryptococcal infection uncommonly presents with pulmonary manifestations and even more rarely so as massive bilateral effusions. Pleural involvement is usually associated with underlying pulmonary parenchymal lesions and is unusual while on antifungal therapy. We report a patient with cryptococcal meningitis who, while on intravenous 5-flucytosine and amphotericin B, developed life-threatening bilateral massive pleural effusions with evidence of spontaneous resolution, consistent with prior hypothesis of antigenic stimulation as the cause of pleural involvement.

Keywords: cryptococcosis; pleural effusions
PMCID: PMC1741239  PMID: 10533638
7.  The Unusual Presentation of a Usual Organism – the Changing Spectrum of the Clinical Manifestations of Plasmodium Vivax Malaria in Children: A Retrospective Study 
Background: Malaria is a major public health problem in the south-east Asian region. Among all countries in the SE Asian region the highest number of cases and deaths are reported from India. Children below 14 years of age contribute to approximately 42% of all the deaths. A majority of the deaths are attributed to severe malaria which is caused by Plasmodium falciparum. It is considered that causes a benign causing febrile illness without significant complications. However, in recent years, the spectrum of is shifting from being the cause of benign fever, to more severe complications. There have been case reports of complications like thrombocytopaenia, cerebral malaria, a disseminated intravascular coagulation, the acute respiratory distress syndrome, hepatic dysfunction and renal involvement. Most of the case reports are from the adult population, with an occasional occurrence of paediatric cases.
Objective: To highlight the increasing number of severe manifestations in P.vivax malaria in the children who were admitted in the malaria transmission season of 2011, at a tertiary care hospital.
Design: A descriptive, cross-sectional study.
Material and Methods:
Study Subjects: Children with an acute febrile illness of a duration of < 7 days, which was confirmed as Plasmodium vivax positive malaria by testing the peripheral smears and/or by Rapid Diagnostic Testing, who were admitted in the paediatric ward of a tertiary care hospital in New Delhi (India), during May 2011 to October 2011, Case records of context cases were analysed retrospectively.
Statistics: The data was summarised by calculating the rates, ratios, proportions, means, standard deviations and the 95% confidence intervals. The Chi square test was applied to assess the significant difference between two qualitative variables.
Results: Among the case records of 54 patients, 40.7% were below 5 years. 61% were males and 38.9% were females. Besides hepatomegaly and splenomegaly which were the most common symptoms, which were seen in 81.5% and 72.2% children respectively, the various unusual manifestations seen were severe thrombocytopaenia (37%), jaundice with deranged LFT values (25.9%), abnormal bleeding (18.5%), impaired consciousness with a GCS of < 9 (18.5%), severe anaemia (14.8%), hypotension (11.1%), repeated convulsions (7.6%), pulmonary oedema/ARDS (5.6%) and ascites (5.6%). One case each showed haemoglobinuria, and pleural effusion.
Conclusion: Plasmodium vivax is emerging as a cause of severe malaria. There is a further need to study the pathophysiology, virulence factors and the molecular mechanisms which are involved in malaria.
PMCID: PMC3809649  PMID: 24179910
Plasmodium vivax malaria; Children; Complications
8.  A case of Meigs syndrome mimicking metastatic breast carcinoma 
Adnexal masses are not uncommon in patients with breast cancer. Breast cancer and ovarian malignancies are known to be associated. In patients with breast cancer and co-existing pleural effusions, ascites and adnexal masses, the probability of disseminated disease is high. Nevertheless, benign ovarian masses can mimic this clinical picture when they are associated with Meigs' syndrome making the work-up and management of these patients challenging. To our knowledge, there are no similar reports in the literature and therefore we present this case to highlight this entity.
Case presentation
A 56-year old woman presented with a 4 cm, grade 2, invasive ductal carcinoma of her left breast. Pre-treatment staging investigations showed a 13.5 cm mass in her left ovary, a small amount of ascites and a large right pleural effusion. Serum tumour markers showed a raised CA125 supporting the malignant nature of the ovarian mass. The cytology from the pleural effusion was indeterminate but thoracoscopic biopsy failed to show malignancy. The patient was strongly against mastectomy and she was commenced on neo-adjuvant Letrozole 2.5 mg daily with a view to perform breast conserving surgery. After a good response to the hormone manipulation, the patient had breast conserving surgery, axillary sampling and laparoscopic excision of the ovarian mass which was eventually found to be a benign ovarian fibroma.
Despite the high probability of disseminated malignancy when an ovarian mass associated with ascites if found in a patient with a breast cancer and pleural effusion, clinicians should be aware about rare benign syndromes, like Meigs', which may mimic a similar picture and mislead the diagnosis and management plan.
PMCID: PMC2633000  PMID: 19161612
9.  The Clinicopathologic Manifestations of Plasmodium Vivax Malaria in Children: A Growing Menace 
Context: Today, India faces increasing morbidity and mortality due to malaria, which is a global health burden. Plasmodium vivax which was once considered to have a benign course, is now being increasingly associated with complicated malaria. Studies which have been done on the increasing virulence of P. Vivax in children, are exceptionally rare.
Aims: This study has addressed some of the hitherto unanswered questions, such as: This study has tried to explore the wide spectrum of severe illnesses which are associated with P.vivax malaria in children.Other co-morbid conditions, which include a co-infection with P.falciparum, have been excluded with great care, to assess the increased virulence of P. Vivax.The present study was focused on the paediatric population with a large sample size of 168 subjects.
Settings and Design: This was an observational retrospective analysis on the clinicopathologic manifestations of the paediatric cases which were admitted with severe malaria due to a mono-infection with Plasmodium vivax, in a tertiary-care centre in the national capital region, India.
Methods and Material: The diagnosis of the mono-infection with P. Vivax malaria was established by making peripheral blood films (PBFs) and by doing rapid diagnostic tests. The severe forms of malaria were categorized as per the World Health Organization guidelines and the clinical and laboratory findings in these cases of complicated malaria were studied.
Statistics: A descriptive statistical analysis was done by using the SPSS software and an Excel worksheet.
Results: This comprehensive study revealed a multisystem involvement. Abdominal manifestations were observed in 75(45.8%) cases (which included hepatosplenomegaly, hepatomegaly, splenomegaly and ascites) and hepatic dysfunction and jaundice were observed in 28(16.7%) cases. The haematological tests showed moderate to severe anaemia in 151(89.9%) cases and thrombocytopaenia in 138(82.1%) cases. Petechiae were noted in 45(26.8%) cases and a gross bleeding was noted in 9(5.3%) cases. The respiratory findings which included tachypnoea, pleural effusions and ARDS were observed in 22(13.1%) cases. Renal dysfunction was noted clinically in 20(11.9%) cases and biochemically in 16(9.5%) cases. Shock was observed in 7(4.1%) cases, cerebral malaria was observed in 10(5.9%) cases and hypoglycaemia was observed in 5(3%) cases. Multi-organ dysfunction was detected in 11(6.54%) cases. The complications were more severe in the younger children (0-5 years).
Conclusions: A mono-infection with P. Vivax may lead to severe malaria and this increased virulence has resulted in the changing picture of P. Vivax malaria, leading to a spectrum of complications which are similar to those which are traditionally associated with P. Falciparum.
PMCID: PMC3681056  PMID: 23814729
Plasmodium vivax; Complicated malaria; Severe malaria
10.  Massive right-sided hemorrhagic pleural effusion due to pancreatitis; a case report 
Hemorrhagic pleural effusion, especially in the right hemithorax rarely occurs as the sole presentation of pancreatitis.
Case Presentation
This article reports massive right-sided hemorrhagic pleural effusion as the sole manifestation of pancreatitis in a 16-year-old Iranian boy. The patient referred to Nemazee Hospital, the main hospital of southern Iran, with right-sided shoulder and chest pain accompanied with dyspnea. His chest x-ray showed massive right-sided pleural effusion. The pleural fluid amylase was markedly elevated (8840 U/L), higher than that in the serum (3318 U/L). Abdominal CT scan showed a cystic structure measuring about 5·2 cm in the head of pancreas, highly suggestive of a pancreatic pseudocyst. Pleural effusion resolved after 3 weeks of chest tube insertion but not completely. After this period of conservative therapy another CT scan showed that pseudocyst was still in the head of pancreas. So, external drainage was done with mushroom insertion and the patient was discharged after 40 days of hospitalization. The cause of pancreatitis could not be identified.
Pancreatitis should be taken into consideration when hemorrhagic pleural effusion, especially in the right hemithorax occurs.
PMCID: PMC362879  PMID: 15018626
Hemorrhagic pleural effusion; Pancreatitis; Cause
11.  Extracavitary Manifestation of Primary Effusion Lymphoma as a Right Atrial Mass 
Case Reports in Oncology  2013;6(1):114-118.
Primary effusion lymphoma (PEL) is a subset of large B cell lymphomas and has been mostly associated with human immunodeficiency virus infection. Rare cases have been reported in organ transplant recipients and chronic hepatitis C patients. It typically presents as an effusion in the pleural and pericardial spaces but rarely disseminates. However, involvement of the gastrointestinal tract, lymph nodes and bone marrow has been reported. Diagnosis is based on characteristic clinical, histopathological and immunohistochemical features. We present a case with a right atrial mass which tested positive for human herpes virus 8 (HHV-8), CD20, CD30 and lambda light chains and negative for CD138, kappa light chain, PAX5, Epstein-Barr virus, latent membrane protein 1, CD2, CD3, CD8 and CD56. Bilateral pleural effusions and pericardial effusions were noted which tested positive for HHV-8, CD30 and CD45. The patient responded well to the R-EPOCH regimen with complete resolution of the effusions and a significant decrease in the size of the right atrial mass. This case report illustrates the atypical manifestation of PEL as a right atrial mass.
PMCID: PMC3618032  PMID: 23569445
Primary effusion lymphoma; Right atrial mass; R-EPOCH; Human herpes virus 8
12.  An unusual presentation of cirrhotic pleural effusion in a patient with no ascites: a case report 
Cases Journal  2009;2:6767.
Pleural effusion that develops in a patient with cirrhosis and portal hypertension, in the absence of cardiopulmonary disease, is termed hepatic hydrothorax. Hepatic hydrothorax very rarely presents in the absence of ascites. Although the exact mechanism is somewhat controversial, pleural effusion occurs when ascitic fluid moves through diaphragmatic defects which are opened up by increased intra-abdominal pressure. We report a case report of cirrhotic pleural effusion in a patient with no clinical or radiographic evidence of ascites and discuss the pathogenesis, diagnosis and management of this condition.
PMCID: PMC2769311  PMID: 19918541
13.  Bilateral pleural effusion as an initial manifestation of multiple myeloma: A case report and literature review 
Multiple myeloma (MM) is a rare type of malignant hematological neoplasm. Although primarily involving the bone marrow, MM has a significant risk of metastasizing to other organs and may present with various clinical symptoms. However, the involvement of the respiratory system in the course of MM is extremely uncommon, particularly presenting with bilateral pleural effusion as the sole initial manifestation, which may result in a delayed diagnosis of MM. The present study describes the extremely rare case of a patient with MM presenting with myelomatous pleural effusion (MPE). The 78-year-old patient was admitted to the Department of Respiratory Medicine, Taizhou People’s Hospital (Taizhou, China) in March 2014, complaining of persistent dyspnea. Following admission, chest computed tomography scans revealed bilateral pleural effusion and a small amount of pericardial effusion, but no evident mass lesion. Thoracentesis was performed and the resulting pleural effusion was exudative and slightly bloody. In the following cytological examination, myeloma cells were identified in the pleural effusion. The patient was diagnosed definitively with MM following a histopathological study of the bone marrow aspiration. Therefore, the observations of the present case report may promote the consideration of MM in the differential diagnosis of patients with unexplained and refractory pleural effusion. The present study also reviewed the literature with regard to the association between MM and pleural effusion.
PMCID: PMC4316953  PMID: 25667674
multiple myeloma; pleural effusion
14.  Meigs syndrome presenting with axillary vein thrombosis and lymphadenopathy: a case report 
Meigs syndrome is a rare condition, occurring in less than 1% of ovarian tumors and has the characteristic features of a benign ovarian tumor, ascites and a pleural effusion. We present a case of Meigs syndrome in a young patient presenting initially with an axillary vein thrombosis and local lymphadenopathy.
Case presentation
A 28-year-old Caucasian woman presented with a short history of right arm swelling and shortness of breath as a result of an axillary vein thrombosis and pulmonary embolus.
The initial assessment also demonstrated right axillary and subclavian lymphadenopathy, a pleural effusion, ascites and a large ovarian mass. Serum levels of the tumor markers human chorionic gonadotropin and alpha-fetoprotein were normal and the CA-125 level was only moderately elevated.
The combination of thrombosis, lymphadenopathy and an ovarian mass raised the possibility of a disseminated malignancy potentially an epithelial ovarian cancer, a germ cell tumor or an ovarian sex cord-stromal tumor.
Surgery, performed after a short period of anticoagulation, demonstrated a 13.5cm ovarian cellular fibroma of low malignant potential. Postoperatively the patient made an excellent recovery and the ascites, pleural effusion and lymphadenopathy all resolved promptly.
In Meigs syndrome the classical findings of ascites, pleural effusion in combination with an ovarian mass can mimic disseminated malignancy but resolve spontaneously after surgery. In this current case, the patient also had lymphadenopathy and venous thrombosis, two other findings that are frequently associated with malignancy and was acutely unwell at presentation.
It is unclear if the thrombosis and lymphadenopathy were simply coincidental or shared the same etiology as the ascites and pleural effusion. This case indicates that Meigs syndrome may on occasion present with additional findings that can further mimic disseminated malignancy and may lead to diagnostic uncertainty.
PMCID: PMC3750274  PMID: 23856407
Ascites; Meigs syndrome; Ovarian cancer; Thrombosis
15.  A distinctive colour associated with high iodine content in malignant pleural effusion from metastatic papillary thyroid cancer: a case report 
Pleural effusions are a common clinical problem and affect about one million people in the United States and United Kingdom each year. Over 60 causes of pleural effusion have been identified; establishing the definitive aetiology can be difficult, and often requires invasive procedures. Guidelines state that macroscopic examination of the fluid should be the first step in determining the aetiology of a pleural effusion. Papillary thyroid carcinoma is an uncommon cause of malignant pleural effusion, with only 10 cases reported in the literature, their physical characteristics and composition having been rarely described. We describe for the first time a distinctive brown colour of the malignant effusion (despite centrifugation) from a rare case of metastatic papillary thyroid cancer to the pleura, associated with a high pleural fluid iodine content. Such a characteristic may be useful in expediting diagnosis of a malignant pleural effusion in the appropriate clinical context.
Case presentation
We present the case of a 71-year-old Caucasian man with metastatic papillary thyroid cancer; a large, long-standing, right-sided pleural effusion and a 83-fold higher pleural thyroglobulin level compared to corresponding serum, supporting this malignancy as the cause of the patient’s effusion. The pleural fluid had a distinctive pigmentation similar to iodine-containing antiseptic preparations. Biopsy during medical thoracoscopy confirmed metastatic papillary thyroid carcinoma. Analysis of pleural fluid showed a pleural thyroglobulin level over 80 times that of serum levels (29,000μg/L versus 350ug/L). Pleural fluid iodine content was 23,000ug/L and may account for the fluid’s distinctive pigment, as iodine is an essential component in thyroglobulin and thyroid hormone synthesis.
Pleural fluid pigmentation may aid diagnosis in the appropriate clinical setting. A distinctive iodine-like brown colour of pleural fluid may represent elevated iodine content and should raise consideration of metastatic thyroid cancer as a cause for a pleural effusion.
PMCID: PMC3680221  PMID: 23724969
Pleural effusion; Iodine; Thyroglobulin; Diagnosis; Thyroid; Carcinoma; Colour
16.  Superoxide dismutase 2 as a marker to differentiate tuberculous pleural effusions from malignant pleural effusions 
Clinics  2014;69(12):799-803.
Our previous study demonstrated that superoxide dismutase levels were higher in tuberculous pleural effusions than in malignant pleural effusions, but that this difference could not be used to discriminate between the two. The objective of the present study was to investigate the levels of superoxide dismutase 2 in pleural effusions and to evaluate the diagnostic significance of pleural effusion superoxide dismutase 2.
Superoxide dismutase 2 concentrations were determined in pleural effusions from 54 patients with tuberculous pleural effusion and 33 with malignant pleural effusion using an enzyme-linked immunosorbent assay (ELISA) kit. Pleural effusion interferon gamma and tumor necrosis factor alpha levels were also analyzed by ELISA. The Mann-Whitney U test was used to evaluate the significance of differences. Associations between superoxide dismutase 2 concentrations and sex, age and smoking habits were assessed using Spearman's or Pearson's correlation coefficient analysis. Receiver operator characteristic analysis was performed to evaluate the value of superoxide dismutase 2 levels in the discrimination of tuberculous pleural effusion from malignant pleural effusion.
Superoxide dismutase 2 levels were significantly higher in patients with tuberculous pleural effusion compared with those with malignant pleural effusion (p<0.05). When superoxide dismutase 2 was used to differentiate between tuberculous pleural effusions and malignant pleural effusions, the area under the receiver operator characteristic curve was 0.909 (95% confidence interval, 0.827-0.960; p<0.01). With a cut-off value of 54.2 ng/mL, the sensitivity, specificity, positive likelihood ratio and negative likelihood ratio were 75.8% (95%CI: 57.7-88.9%), 98.1% (95%CI: 90.1-99.7%), 40.91 and 0.25, respectively. Furthermore, significant correlations between pleural effusion superoxide dismutase 2 and interferon gamma (r = 0.579, p<0.01) and between pleural effusion superoxide dismutase 2 and tumor necrosis factor alpha (r = 0.396, p<0.01) were observed.
Pleural effusion superoxide dismutase 2 can serve as a biomarker for differentiating between tuberculous pleural effusions and malignant pleural effusions. Because of the high correlations of superoxide dismutase 2 with pleural effusion interferon gamma and tumor necrosis factor alpha levels, this marker may act as an inflammatory factor that plays an important role in the development of tuberculous pleural effusion.
PMCID: PMC4286673  PMID: 25627990
Superoxide Dismutase 2; Tuberculous Pleural Effusion; Malignant Pleural Effusion; Biomarker
17.  Bilateral pleural effusion and interstitial lung disease as unusual manifestations of kikuchi-fujimoto disease: case report and literature review 
Kikuchi-Fujimoto's disease (KFD), also called histiocytic necrotizing lymphadenitis, is a rare, idiopathic and self-limited condition usually characterized by cervical lymphadenopathy and fever, most often affecting young patients. Aetiology is unknown. Differential diagnosis includes mainly malignant lymphoma, tuberculous lymphadenitis and systemic lupus erythematosus (SLE), so early diagnosis is crucial. Pleuropulmonary involvement due to isolated KFD has been seldom reported.
Case Presentation
a 32-year-old man, on treatment for iatrogenic hypothyroidism, was admitted due to high grade fever and painful cervical lymphadenopathies. KFD was diagnosed by lymph node biopsy. Some days after admission the patient got worse, he developed generalized lymphadenopathy, bilateral pleural effusion and interstitial lung disease. All of them resolved with prednisone and after two years of following up he remains asymptomatic and without evidence of any other associated disease.
Pleural effusion and interstitial lung disease are very uncommon manifestations of KFD. In our experience, treatment with oral prednisone was effective.
PMCID: PMC2991292  PMID: 21054856
18.  Efficacy of Pneumococcal Nontypable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV) in Young Latin American Children: A Double-Blind Randomized Controlled Trial 
PLoS Medicine  2014;11(6):e1001657.
In a double-blind randomized controlled trial, Xavier Saez-Llorens and colleagues examine the vaccine efficacy of PHiD-CV against community-acquired pneumonia in young children in Panama, Argentina, and Columbia.
Please see later in the article for the Editors' Summary
The relationship between pneumococcal conjugate vaccine–induced antibody responses and protection against community-acquired pneumonia (CAP) and acute otitis media (AOM) is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on these end points. The primary objective was to demonstrate vaccine efficacy (VE) in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ≥ 40 µg/ml); other protocol-specified outcomes were also assessed.
Methods and Findings
This phase III double-blind randomized controlled study was conducted between 28 June 2007 and 28 July 2011 in Argentine, Panamanian, and Colombian populations with good access to health care. Approximately 24,000 infants received PHiD-CV or hepatitis control vaccine (hepatitis B for primary vaccination, hepatitis A at booster) at 2, 4, 6, and 15–18 mo of age. Interim analysis of the primary end point was planned when 535 first B-CAP episodes, occurring ≥2 wk after dose 3, were identified in the per-protocol cohort. After a mean follow-up of 23 mo (PHiD-CV, n = 10,295; control, n = 10,201), per-protocol VE was 22.0% (95% CI: 7.7, 34.2; one-sided p = 0.002) against B-CAP (conclusive for primary objective) and 25.7% (95% CI: 8.4%, 39.6%) against World Health Organization–defined consolidated CAP. Intent-to-treat VE was 18.2% (95% CI: 5.5%, 29.1%) against B-CAP and 23.4% (95% CI: 8.8%, 35.7%) against consolidated CAP. End-of-study per-protocol analyses were performed after a mean follow-up of 28–30 mo for CAP and invasive pneumococcal disease (IPD) (PHiD-CV, n = 10,211; control, n = 10,140) and AOM (n = 3,010 and 2,979, respectively). Per-protocol VE was 16.1% (95% CI: −1.1%, 30.4%; one-sided p = 0.032) against clinically confirmed AOM, 67.1% (95% CI: 17.0%, 86.9%) against vaccine serotype clinically confirmed AOM, 100% (95% CI: 74.3%, 100%) against vaccine serotype IPD, and 65.0% (95% CI: 11.1%, 86.2%) against any IPD. Results were consistent between intent-to-treat and per-protocol analyses. Serious adverse events were reported for 21.5% (95% CI: 20.7%, 22.2%) and 22.6% (95% CI: 21.9%, 23.4%) of PHiD-CV and control recipients, respectively. There were 19 deaths (n = 11,798; 0.16%) in the PHiD-CV group and 26 deaths (n = 11,799; 0.22%) in the control group. A significant study limitation was the lower than expected number of captured AOM cases.
Efficacy was demonstrated against a broad range of pneumococcal diseases commonly encountered in young children in clinical practice.
Trial registration NCT00466947
Please see later in the article for the Editors' Summary
Editors' Summary
Pneumococcal diseases are illnesses caused by Streptococcus pneumoniae bacteria, pathogens (disease-causing organisms) that are transmitted through contact with infected respiratory secretions. S. pneumoniae causes mucosal diseases–infections of the lining of the body cavities that are connected to the outside world–such as community-acquired pneumonia (CAP; lung infection) and acute otitis media (AOM; middle-ear infection). It also causes invasive pneumococcal diseases (IPDs) such as septicemia and meningitis (infections of the bloodstream and the covering of the brain, respectively). Although pneumococcal diseases can sometimes be treated with antibiotics, CAP and IPDs are leading global causes of childhood deaths, particularly in developing countries. It is best therefore to avoid S. pneumoniae infections through vaccination. Vaccination primes the immune system to recognize and attack pathogens rapidly and effectively by exposing it to weakened or dead pathogens or to pathogen molecules that it recognizes as foreign (antigens). Because there are more than 90 S. pneumoniae variants (“serotypes”), each characterized by a different antigenic polysaccharide (complex sugar) coat, S. pneumoniae vaccines have to include antigens from multiple serotypes. For example, the PHiD-CV vaccine contains polysaccharides from ten S. pneumoniae serotypes.
Why Was This Study Done?
Although in most countries PHiD-CV has been licensed for protection against IPD and pneumococcal AOM, at the time of study, it was not known how well it protected against CAP and overall AOM, which are important public health problems. In this double-blind randomized controlled trial (the Clinical Otitis Media and Pneumonia Study; COMPAS), the researchers investigate the efficacy of PHiD-CV against CAP and AOM and assess other clinical end points, such as IPD, in Latin American infants. Double-blind randomized controlled trials compare the effects of interventions by assigning study participants to different interventions randomly and measuring predefined outcomes without the study participants or researchers knowing who has received which intervention until the trial is completed. Vaccine efficacy is the reduction in the incidence of a disease (the number of new cases that occur in a population in a given time) among trial participants who receive the vaccine compared to the incidence among participants who do not receive the vaccine.
What Did the Researchers Do and Find?
The researchers enrolled around 24,000 infants living in urban areas of Argentina, Panama, and Colombia. Half the infants were given PHiD-CV at 2, 4, and 6 months of age and a booster dose at age 15–18 months. The remaining infants were given a hepatitis control vaccine at the same intervals. The trial's primary end point was likely bacterial CAP (B-CAP) –radiologically confirmed CAP, with the airspaces (alveoli) in the lungs filled with liquid instead of gas (alveolar consolidation) or with non-alveolar infiltrates and raised blood levels of C-reactive protein (a marker of inflammation). In a planned interim analysis, which was undertaken after an average follow-up of 23 months, the vaccine efficacy in the per-protocol cohort (the group of participants who actually received their assigned intervention) was 22% against B-CAP. Intent-to-treat vaccine efficacy in the interim analysis (which considered all the trial participants regardless of whether they received their assigned intervention) was 18.2%. At the end of the study (average follow up 30 months), the vaccine efficacy against B-CAP was 18.2% and 16.7% in the per-protocol and intent-to-treat cohorts, respectively. Per-protocol vaccine efficacies against clinically confirmed AOM and vaccine serotype AOM were 16.1% and 67.1%, respectively. Against any IPD and against vaccine serotype IPD, the respective vaccine efficacies were 65% and 100%. Finally, about one-fifth of children who received PHiD-CV and a similar proportion who received the control vaccine experienced a serious adverse event (for example, gastroenteritis); 19 children who received PHiD-CV died compared to 26 children who received the control vaccine.
What Do These Findings Mean?
These findings indicate that in Latin America, a region with an intermediate burden of pneumococcal disease, PHiD-CV is efficacious against a broad range of pneumococcal diseases that often affect young children. The accuracy of these findings may be limited by the withdrawal of 14% of participants from the trial because of adverse media coverage and by the low number of reported cases of AOM. Moreover, because most study participants lived in urban areas, these findings may not be generalizable to rural settings. Despite these and other study limitations, these findings provide new information about the magnitude of the effect of PHiD-CV vaccination against CAP and AOM, two mucosal pneumococcal diseases of global public health importance.
Additional Information
Please access these websites via the online version of this summary at
The US Centers for Disease Control and Prevention provides information for patients and health professionals on all aspects of pneumococcal disease and pneumococcal vaccination, including personal stories
Public Health England provides information on pneumococcal disease and on pneumococcal vaccines
The not-for-profit Immunization Action Coalition has information on pneumococcal disease, including personal stories
The GAVI Alliance provides information about pneumococcal disease and the importance of vaccination
MedlinePlus has links to further information about pneumococcal infections, including pneumonia and otitis media (in English and Spanish)
More information about COMPAS is available
The European Medicines Agency provides information about PHiD-CV (Synflorix)
PMCID: PMC4043495  PMID: 24892763
19.  Myelomatous Pleural Effusion 
Plasma cell myeloma is an uncommon disease which, besides primarily involving the bone marrow, has a tendency to involve other organs thus presenting with different clinical manifestations. While pleural effusions are infrequent in this disease, true myelomatous pleural effusions are extremely rare. We report the case of a middle-aged Omani man with relapsed plasma cell myeloma who developed bilateral pleural effusions. The diagnosis of myelomatous pleural effusion was made by finding many abnormal plasma cells as well as a high level of a monoclonal protein (IgG κ) in the pleural fluid. In spite of a good initial response to therapy, the patient had progressive disease and died 6 months later with bacterial sepsis. We present a review of the literature that indicates the rarity of such a manifestation and its association with poor prognosis and short survival.
PMCID: PMC3121032  PMID: 21969899
Multiple myeloma; Plasma cells; Pleural effusion; Case report; Oman
20.  Factors Associated with Dengue Shock Syndrome: A Systematic Review and Meta-Analysis 
The pathogenesis of dengue shock syndrome (DSS, grade 3 and 4) is not yet completely understood. Several factors are reportedly associated with DSS, a more severe form of dengue infection that reportedly causes 50 times higher mortality compared to that of dengue patients without DSS. However, the results from these reports remain inconclusive. To better understand the epidemiology, clinical manifestation, and pathogenesis of DSS for development of new therapy, we systematically reviewed and performed a meta-analysis of relevant studies that reported factors in both DSS and dengue hemorrhagic fever (DHF, grade 1 and 2) patients.
Methods and Findings
PubMed, EMBASE, Scopus, Google Scholar, Dengue Bulletin, Cochrane Library, Virtual Health Library, and a manual search of reference lists of articles published before September 2010 were used to retrieve relevant studies. A meta-analysis using fixed- or random-effects models was used to calculate pooled odds ratios (OR) or event rate with corresponding 95% confidence intervals. Assessment of heterogeneity and publication bias, meta-regression analysis, subgroup analysis, sensitivity analysis, and analysis of factor-specific relationships were further performed. There were 198 studies constituting 203 data sets that met our eligibility criteria. Our meta-regression analysis showed a sustained reduction of DSS/dengue hemorrhagic fever (DHF) ratio over a period of 40 years in Southeast Asia, especially in Thailand. The meta-analysis revealed that age, female sex, neurological signs, nausea/vomiting, abdominal pain, gastrointestinal bleeding, hemoconcentration, ascites, pleural effusion, hypoalbuminemia, hypoproteinemia, hepatomegaly, levels of alanine transaminase and aspartate transaminase, thrombocytopenia, prothrombin time, activated partial thromboplastin time, fibrinogen level, primary/secondary infection, and dengue virus serotype-2 were significantly associated with DSS when pooling all original relevant studies.
The results improve our knowledge of the pathogenesis of DSS by identifying the association between the epidemiology, clinical signs, and biomarkers involved in DSS.
Author Summary
Dengue is one of the most common viral diseases transmitted by infected mosquitoes. It may range from asymptomatic or self-limiting dengue fever (DF) to severe dengue characterized by plasma leakage (dengue hemorrhagic fever, DHF) and dengue shock syndrome (DSS). Death from dengue infection occurs mostly in DSS, and the mortality of DSS is reportedly 50 times higher compared to that of dengue patients without DSS. Several factors associated with DSS have been reported in individual studies; however, the associations for some factors are not observed consistently across studies. Therefore, we conducted a systematic review of the literature to clarify this issue. The study showed persons with younger age, female sex, neurological signs, nausea/vomiting, abdominal pain, gastrointestinal bleeding, increased hemoconcentration, ascites, pleural effusion, hypoalbuminemia, hypoproteinemia, hepatomegaly, increased level of ALT or AST, thrombocytopenia, coagulation dysregulation, secondary infection, and infection of dengue virus serotype 2 are more likely to have DSS. This result improves our knowledge of the clinical manifestation and pathogenesis of DSS.
PMCID: PMC3784477  PMID: 24086778
21.  Polycystic liver disease presenting with an exudative pleural effusion: a case report 
Polycystic liver disease is asymptomatic in 95% of patients. In the remaining 5% it causes symptoms due to the local mass effect of the polycystic liver. We describe the case of a patient who presented with symptoms of a pleural effusion and was also found to have polycystic liver disease. The effusion recurred despite repeated efforts at drainage and only resolved following surgical debridement of the cystic liver.
Case presentation
A 50-year-old Caucasian woman presented with a two-week history of increasing dyspnoea. An examination revealed a large right pleural effusion and gross hepatomegaly. An ultrasound confirmed a large polycystic liver and diagnostic thoracocentesis revealed an exudate, which was sterile to culture. The pleural effusion proved refractory to drainage and our patient underwent surgery to deroof the main hepatic cysts in an attempt to reduce the pressure on her right diaphragm. The histology was compatible with that of polycystic liver disease. No evidence of malignancy was found. After surgery, our patient had no recurrence of her effusion and, to date, has remained asymptomatic from her polycystic liver disease.
The case in this report illustrates that an exudative pleural effusion is a rare complication of polycystic liver disease. We feel that the mechanical effects of a large polycystic liver, and subsequent disruption of sub-diaphragmatic capillaries, resulted in a persistent exudative pleural effusion. Thus, surgical debulking of the hepatic cysts is required to manage these effusions.
PMCID: PMC3349473  PMID: 22502729
22.  Hepatitis A and E seroprevalence and associated risk factors: a community-based cross-sectional survey in rural Amazonia 
BMC Infectious Diseases  2014;14(1):458.
Hepatitis A virus (HAV) and hepatitis E virus (HEV) are both transmitted by the faecal-oral route, and represent common causes of acute hepatitis in developing countries. The endemicity of HAV infection has shifted from high to moderate in Brazil. Human cases of HEV infection seem to be rare, although the virus has been detected in swine livestock and effluents of slaughterhouses. This study was to determine the epidemiology of hepatitis A and E in one of the largest agricultural settlements in the Amazon Basin of Brazil.
Serum samples collected from 397 individuals aged between 5 and 90 years during a population-based cross-sectional survey were tested for anti-HAV and anti-HEV antibodies. Associated risk factors and spatial clustering of HAV and HEV seropositivity were also analyzed.
The overall rate of HAV seropositivity was 82.9% (95% confidence interval (CI), 79.2-86.6%). Multilevel logistic regression analysis identified increasing age (in years; odds ratio (OR), 1.097; 95% CI, 1.050-1.147; P < 0.001) and crowding (OR, 1.603; 95% CI, 1.054-2.440; P = 0.028) as significant risk factors for HAV seropositivity. Anti-HEV IgG was detected in 50/388 settlers (12.9%, 95% CI, 9.5-16.2%). Anti-HEV IgM was detected in 7/43 (16.3%) anti-IgG positive samples, and 4 of them had a confirmed result by immunoblot. Increasing age was the only significant determinant of HEV seropositivity (OR, 1.033; 95% CI, 1.016-1.050; P < 0.001). No significant spatial clustering of HAV and HEV seropositivity was detected in the area.
Both HAV and HEV are endemic, with differing rates of infection in children and adults in this rural setting of the Brazilian Amazon. Anti-HEV prevalence was considerably higher than those previously reported in Brazil. The detection of HEV- specific IgM antibodies in four asymptomatic individuals is highly suggestive of the circulation of HEV in this rural population.
PMCID: PMC4152586  PMID: 25149658
Hepatitis A; Hepatitis E; Seroprevalence; Amazon basin
23.  The Global Spread of Hepatitis C Virus 1a and 1b: A Phylodynamic and Phylogeographic Analysis 
PLoS Medicine  2009;6(12):e1000198.
Using phylodynamic and phylogeographic methods, Angelos Hatzakis and colleagues find that the global spread of Hepatitis C virus coincided with widespread use of transfused blood and with the expansion of intravenous drug use.
Hepatitis C virus (HCV) is estimated to affect 130–180 million people worldwide. Although its origin is unknown, patterns of viral diversity suggest that HCV genotype 1 probably originated from West Africa. Previous attempts to estimate the spatiotemporal parameters of the virus, both globally and regionally, have suggested that epidemic HCV transmission began in 1900 and grew steadily until the late 1980s. However, epidemiological data suggest that the expansion of HCV may have occurred after the Second World War. The aim of our study was to elucidate the timescale and route of the global spread of HCV.
Methods and Findings
We show that the rarely sequenced HCV region (E2P7NS2) is more informative for molecular epidemiology studies than the more commonly used NS5B region. We applied phylodynamic methods to a substantial set of new E2P7NS2 and NS5B sequences, together with all available global HCV sequences with information in both of these genomic regions, in order to estimate the timescale and nature of the global expansion of the most prevalent HCV subtypes, 1a and 1b. We showed that transmission of subtypes 1a and 1b “exploded” between 1940 and 1980, with the spread of 1b preceding that of 1a by at least 16 y (95% confidence interval 15–17). Phylogeographic analysis of all available NS5B sequences suggests that HCV subtypes 1a and 1b disseminated from the developed world to the developing countries.
The evolutionary rate of HCV appears faster than previously suggested. The global spread of HCV coincided with the widespread use of transfused blood and blood products and with the expansion of intravenous drug use but slowed prior to the wide implementation of anti-HCV screening. Differences in the transmission routes associated with subtypes 1a and 1b provide an explanation of the relatively earlier expansion of 1b. Our data show that the most plausible route of the HCV dispersal was from developed countries to the developing world.
Please see later in the article for the Editors' Summary
Editors' Summary
About 150 million people (3% of the world's population) harbor long-term (chronic) infections with the hepatitis C virus (HCV) and about 3–4 million people become infected with this virus every year. HCV—a leading cause of chronic hepatitis (inflammation of the liver)—is spread through contact with infected blood. Transmission routes include medical procedures (for example, transfusions with unscreened blood) and needle-sharing among intravenous drug users. This second transmission route is the most common one in developed countries where blood is now routinely screened before being used in transfusions. HCV infection can cause a short-lived illness characterized by tiredness and jaundice (yellow skin and eyes), but most newly infected people progress to a symptom-free, chronic infection that can eventually cause liver cirrhosis (scarring) and liver cancer. HCV infections can be treated with a combination of two expensive drugs called interferon and ribavirin, but these drugs are ineffective in many patients.
Why Was This Study Done?
Noone knows for sure where HCV originated although there is some evidence that it appeared first in West Africa or Southeast Asia. It is also unclear when the current HCV epidemic began. In this study, the researchers try to elucidate both the timescale and route of the global spread of the HCV epidemic by analyzing the genome sequence of HCV samples collected at different times and places. HCV is a ribonucleic acid (RNA) virus. That is, it stores the information it needs to replicate itself—its genome—as a series of “ribonucleotides.” Like other RNA viruses, the HCV genome continually accumulates small changes (mutations) and, over time, HCV has evolved into several different “genotypes,” each of which has several distinct subtypes. Furthermore, the viruses within a single subtype have subtly different genomes. By analyzing this viral diversity using complex “phylodynamic” and “phylogeographic” methods, scientists can build up a picture of how HCV has evolved in populations and how it has spread to reach its current geographical distribution.
What Did the Researchers Do and Find?
By examining the genomes of HCV samples collected between 1994 and 2006 at the Athens University Medical School (Greece), the researchers first defined a variable region of HCV called E2P7NS2 that is more informative for phylodynamic studies than the NS5B region that has been used in previous studies. They then retrieved the sequences of both regions for subtype 1a and 1b samples collected over the past 20–30 years in the Los Alamos HCV sequence database; HCV subtypes 1a and 1b cause 60% of global HCV infections. The researchers' phylodynamic analyses of these globally representative sequences (collected in the USA, Germany, Switzerland, and Greece) indicate that the transmission of HCV subtype 1a occurred at a low rate from 1906 until the 1960s, at which time there was an explosive increase in its transmission rate. Similarly, subtype 1b transmission occurred at a low rate from 1922 until the late 1940s but then increased exponentially. From 1980 onwards, the prevalence of both subtypes stabilized at a high level. The researchers' phylogeographic analyses (which considered 1a and1b NS5B sequences collected in 21 and 29 countries, respectively) suggest that HCV subtypes 1a and 1b may have spread from the developed to the developing world.
What Do These Findings Mean?
These findings indicate that the epidemic of HCV subtype 1b began in the 1940s when the use of transfused blood and blood products became widespread whereas the start of the subtype 1a epidemic coincided with the expansion of injected drug use that occurred in the 1960s. The findings also suggest that the transmission rates of both subtypes may have slowed before the widespread implementation of HCV screening in the early 1990s, possibly because the medical community was aware by then of the general risks associated with blood contamination. Finally, these findings provide new insights into how the HCV epidemic spread around the world and suggest that HCV may be evolving faster than previously thought. However, because this study relied on a small number of samples collected over a short time period, its findings need to be confirmed in larger studies.
Additional Information
Please access these Web sites via the online version of this summary at
The World Health Organization provides detailed information about hepatitis C and HCV
The US Centers for Disease Control and Prevention provides information on hepatitis C for the public and for health professionals (information is also available in Spanish)
The US National Institute of Diabetes and Digestive and Kidney Diseases provides basic information on hepatitis C (in English and Spanish)
MedlinePlus provides links to further resources on hepatitis C
The Los Alamos HCV database is available
The US National Center for Biotechnology Information provides a science primer on how scientists reconstruct evolutionary pathways from sequence information
PMCID: PMC2795363  PMID: 20041120
24.  Sarcoidosis in a 65-year-old woman presenting with a lung mass and pericardial effusion: a case report 
Sarcoidosis is a multi-systemic disorder of unknown origin and most commonly affects the lungs. Diagnosis relies on the presence of non-caseating granulomas on histologic specimens. In high-resolution computed tomography, the most characteristic findings are peribronchovascular thickening, perilymphatic nodular distribution, and bilateral hilar adenopathy. Confluent nodular opacities or large masses are rare manifestations of the disease. It is well recognized that sarcoidosis can mimic infectious, malignant, and granulomatous conditions. Here, we report a case with a high initial index of suspicion for lung malignancy in terms of clinical, lung imaging, and endoscopic findings.
Case presentation
A 65-year-old Caucasian woman, lifelong non-smoker with an unremarkable medical history, presented with a 10-month history of progressive breathlessness, dry cough, fatigue, arthralgias, and mild weight loss. The only significant clinical finding was bilateral enlargement of auxiliary lymph nodes. High-resolution computed tomography revealed a soft tissue density mass at the right hilum which was surrounding and narrowing airways and vascular components, nodules with vascular distribution, enlarged mediastinal lymph nodes, and pericardial effusion. Our patient underwent a bronchoscopy, which revealed the presence of submucosal infiltration and narrowing of the right upper bronchus. Endobronchial biopsies showed non-caseating granulomas. As local sarcoid reactions with non-caseating granulomas can be observed near tumors, our patient underwent video-assisted thoracoscopy and surgical removal of an auxiliary lymph node, both of which confirmed the presence of non-caseating granulomas and the diagnosis of sarcoidosis. She was treated with steroids with improvement of clinical and imaging findings. However, while on a maintenance dose, she presented with a pleural effusion, which, after the diagnostic work-up, proved to be sarcoidosis-related. Treatment with initially high doses of steroids plus a steroid-sparing agent led to resolution of the effusion.
We report a case with a high initial index of suspicion for lung malignancy. Clinicians should always be aware that sarcoidosis enters the differential diagnosis of patients presenting with a lung mass that encases and narrows bronchial and vascular structures with associated pericardial effusion. Rarely, pleural effusion can be the presenting symptom of disease relapse despite maintenance treatment.
PMCID: PMC3443668  PMID: 22937889
Sarcoidosis; Lung cancer; Pleural effusion; Pericardial effusion.
25.  Hepatitis B (prevention) 
Clinical Evidence  2009;2009:0916.
Nearly a third of the world’s population has been infected by hepatitis B at some point, and at least 350 million people have become chronic carriers. Progressive liver damage occurs in up to 25% of carriers. In areas of high endemicity, transmission occurs largely in childhood; from an infected mother to her baby, or between members of a household.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of vaccination against hepatitis B infection in countries with high endemicity? What are the effects of vaccination against hepatitis B infection in countries with low endemicity? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations, such as the US Food and Drug Administration (FDA), and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 51 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: selective vaccination of high-risk individuals; selective vaccination of people with chronic liver disease not caused by hepatitis B; universal vaccination of adolescents; and universal vaccination of infants.
Key Points
Nearly a third of the world's population has been infected by hepatitis B at some point, and at least 350 million people have become chronic carriers. Progressive liver damage occurs in up to 25% of carriers. In areas of high endemicity, transmission occurs largely in childhood, from an infected mother to her baby, or between members of a household.In areas of low endemicity, transmission usually occurs as a result of sexual activity, intravenous drug use, or occupational exposure.The risk of developing hepatitis B depends largely on the vaccination policy of the country of residence, and routine vaccination of all infants is recommended by the WHO.
Selective vaccination of infants with recombinant or plasma-derived vaccines in countries with high endemicity of hepatitis B reduces occurrence and chronic carrier state. Combining vaccine with hepatitis B immunoglobulin is more effective than vaccine alone.
Universal vaccination of infants with recombinant or plasma-derived vaccines, in countries with high endemicity of hepatitis B, reduces the risk of acute hepatitis, chronic carrier state, and complications of chronic infection, and may be more effective than selective vaccination of high-risk individuals. Vaccination of children born to hepatitis B surface antigen (HBsAg)-positive mothers prevents development of a chronic carrier state compared with placebo.
Universal vaccination of infants or adolescents in low-endemic areas may reduce the risk of infection, or of developing a chronic carrier state, but we don't know how different vaccination strategies compare, as no studies have been done.
Selective vaccination of high-risk individuals in countries with low hepatitis B endemicity may prevent acute infection and development of a chronic carrier state. Uptake of vaccination may be low, even in high-risk groups.
Vaccination is associated generally with mild adverse effects, although more serious autoimmune adverse effects can occur rarely.
We don't know whether selective vaccination of people with known chronic liver disease not caused by hepatitis B reduces subsequent infection rates, as few studies have been done.
The evidence reported here is the best available evidence for this type of intervention, and further research is unlikely to change the conclusions reached.
PMCID: PMC2907831  PMID: 21726479

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