Dengue: A growing global health threat

@#Dengue infection, one of the most devastating mosquito-borne viral diseases in humans, is now a significant problem in many countries. The disease, caused by the four dengue virus serotypes, ranges from asymptomatic infection to undifferentiated fever, dengue fever (DF), and severe dengue hemorrhagic fever (DHF) with or without shock. DHF is characterized by fever, bleeding diathesis and a tendency to develop a potentially fatal shock syndrome. Dengue infection with organ impairment mainly involves central nervous system and liver. Consistent hematological Findings include vasculopathy, coagulopathy, and thrombocytopenia. Laboratory diagnosis includes virus isolation, serology, and detection of dengue ribonucleic acid. Successful treatment, which is mainly supportive, depends on early recognition of the disease and careful monitoring for shock. A severity-based revised dengue classification for medical interventions has been developed and validated in many countries. Prevent depends primarily on control of the mosquito vector. The feasibility of a dengue vaccine is high.

Immunogenicity and safety of a DTaP-IPV//PRP-T vaccine (Pentaxim) booster during the second year of life in Thai children primed with an acellular pertussis combined vaccine.

This study assessed the booster immune response to a pentavalent combination vaccine containing diphtheria, tetanus, acellular pertussis, inactivated poliovirus, and conjugated-Hib polysaccharide antigens, (DTaP-IPV//PRP-T, Pentaxim, an AcXim family vaccine) at 18-24 months of age. Study subjects received a three-dose primary vaccination at 2, 4 and 6 months with a hexavalent vaccine containing the same antigens plus recombinant hepatitis B surface antigen. Antibody concentrations were measured immediately before and one month after vaccination. Reactogenicity and safety were evaluated from parent reports. Before the booster dose, 92.9% of the 156 children included in this study still had anti-PRP antibody titers > or = 0.15 microg/ml. Seroprotective concentrations of anti-diphtheria, tetanus and poliovirus antibodies were maintained in 97 to 100% of subjects in the interval between primary and booster vaccination. One month after the booster dose, all subjects had seroprotective anti-PRP (> or = 1 microg/ml), diphtheria and tetanus (> or = 0.1 IU/ml) and poliovirus types 1, 2, 3 (> or = 8 1/dil) antibody levels. At least 92.3% of subjects had 4-fold increases in concentrations of anti-pertussis antigens from pre- to post-booster dose. Geometric mean titers (GMTs) increased from 3.8 to 181.2 EU/ml and from 18.0 to 289.7 EU/ml for anti-PT and anti-FHA, respectively. The anti-PRP GMT increased from 1.6 to 58.0 microg/ml. The pentavalent DTaP-IPV//PRP-T vaccine booster was well tolerated and highly immunogenic, following primary vaccination with a hexavalent vaccine.

Regression of a cervical spinal mass following highly active antiretroviral therapy (HAART) in child with advanced human immunodeficiency virus (HIV) disease.

This report documents a case of infiltrating cervical spinal mass, most likely a spinal tumor, in a girl with HIV infection that regressed following HAART and without treatment of the tumor or any anti-infectives.

D-dimer as an indicator of dengue severity.

Background: Dengue infection is a problem of global concern. The clinical spectrum of the disease varies from an acute febrile course accompanied by mild hemorrhagic manifestations with uneventful recovery to refractory shock and massive bleeding with high mortality. Several mechanisms may be involved in the pathogenesis of bleeding, namely: vasculopathy, thrombocytopenia, coagulopathy and dissiminated intravascular coagulopathy (DIC). Objective: To determine the relationship between D-dimer (DD) levels and clinical outcome in dengue patients. Method: Children with suspected dengue infection admitted to King Chulalongkorn Memorial Hospital were enrolled. D-dimer (DD) was sequentially measured during the course of illness using whole blood and a rapid semiquantitative system (SimpliRed). Diagnosis of dengue infection was confirmed by serology and WHO criteria were used for classifying dengue severity. Results: 41 dengue patients, 22 girls and 19 boys were recruited in the study. The mean age was 9.68 years. There were 12 (29.3 %) cases of dengue fever (DF) and 29 (70.7 %) cases of dengue hemorrhagic fever (DHF). DD was more significantly present in the DHF group (87 %) than in the DF group (13%) (P<0.03). The sensitivity and specificity of DD in predicting severe dengue infection (DHF) were 90% and 67 %, respectively. Sequential analysis of DD showed higher levels at all stages of dengue infection. It correlated with the disease severity. Conclusion: Semiquantitative DD assay measurements in children suffering from dengue infection significantly correlated with dengue severity.

Purpuric-like rash as cutaneous eruptions in parvovirus B19 infection in Thai infant.

An 8-month-old girl presented with fever, rash, and diarrhea. Physical examination revealed multiple well-circumscribed, brownish-black, purpuric-like rashes on the face, arms, and legs with cervical and suboccipital lymphadenopathy. Laboratory findings showed mild anemia with thrombocytopenia and positive polymerase chain reaction for parvovirus 819 DNA in the serum. The patient recovered uneventfully with symptomatic and supportive treatment. Since the infection can manifest in many dermatological patterns, it should also be included in the differential diagnosis of febrile illness with purpuric rash in children.

Childhood shigellosis at King Chulalongkorn Memorial Hospital, Bangkok, Thailand: a 5-year review (1996-2000).

The objective of this study was to evaluate the demographic data and clinical presentation of childhood shigellosis, and to study the microbiological data and antimicrobial susceptibilities of Shigella spp. Nine thousand nine hundred fourteen stool culture specimens from children aged 0-15 years who were treated at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 1996 and 2000 were retrospectively reviewed. Data were collected from microbiological records and medical charts of childhood shigellosis in terms of demographic data, symptoms, signs, and complications of the patients, and the species and antimicrobial susceptibilities of the organisms. The data were analyzed in terms of means, ranges, and percentages. Of 1,523 children whose stool cultures were positive for pathogenic bacteria, 80 (5.3%) were infected with Shigella spp; 34 females and 46 males. The age distribution ranged from 1 day to 13 years with a mean age of 3.6 years. Common clinical presentations included diarrhea (96.6%), fever (77.6%) and vomiting (44.8%); seizures were the most common complication found (27.6%). Watery and mucous were the most common characteristics of stools. The major Shigella spp found was S. sonnei (62.8%), which was susceptible to co-trimoxazole, ampicillin, cefazolin and ciprofloxacin in 2.3, 84.1, 100 and 100%, respectively. A short course of quinolones or oral cephalosporins should be recommended for the treatment of childhood shigellosis in areas with low susceptibility rates to co-trimoxazole and ampicillin.

Concomitant dengue infection and Kawasaki disease in an infant: a case report and literature review.

A previously healthy 11-month-old girl presented with fever and rash for 6 days. Physical examination revealed an irritable infant with a high fever, injected conjunctivae, red cracked lips, posterior auricular lymphadenopathy, hepatomegaly, generalized erythematous maculopapular rash and petechial hemorrhage on trunk, face and extremities. Complete blood count showed atypical lymphocytosis and thrombocytopenia. Dengue infection was initially diagnosed. The persistent fever and clinical manifestations of Kawasaki disease (KD) were observed on day 8 with high erythrocyte sedimentation rate (56 mm/hr). Treatment of KD included intravenous immunoglobulin on day 9 of the illness. Desquamation of the fingers was found on day 15 of the illness. Ectasia of left coronary artery with small aneurysmal dilatation was detected by echocardiography on day 15 of the illness. Hemagglutination-inhibition test and enzyme-linked immunosorbent assay for dengue virus eventually showed a four-fold rising. According to the literature review, this is the second reported case of dengue infection concomitant with KD. The natural course of each disease may be modified and causes some difficulties in diagnosis and management.

Serum and urine sodium levels in dengue patients.

We evaluated serum and urine sodium levels in children with dengue infections. Children with acute febrile illness admitted to Bhumibol Adulyadej Hospital in Bangkok from January 1999 to January 2000 were enrolled. Serum and urine sodium levels were measured before initiating intravenous fluid therapy. Two milliliters of blood were obtained on admission and before discharge to test for anti-dengue virus antibody using the enzyme-linked immunosorbent assay technique. Hyponatremia was defined as a serum sodium level <130 mEq/l and depletion of circulatory volume was defined as a urine sodium level < 20 mEq/l. Out of 93 enrolled patients, 49 were categorized as dengue patients and 44 were as non-dengue patients. Six dengue patients developed shock whereas 43 patients did not. The mean serum sodium level was significantly lower in dengue patients compared to non-dengue patients (p-value < 0.0001). Hyponatremia was 9.7 times more common in dengue patients. Among dengue patients, the mean serum sodium level was significantly lower in shock patients compared to non-shock patients (p-value = 0.003). However, the prevalence of hyponatremia was not different between the two groups. The mean urine sodium level was significantly lower in dengue patients compared to non-dengue patients (p-value < 0.0001). A urine sodium level < or = 20 mEq/l was 8.1 times more common in dengue patients. Among dengue patients, the mean urine sodium level was not significantly different between shock and non-shock patients. In shock patients, a urine sodium level < or = 20 mEq/l was 7.6 times more common.

A phase IV open label study to assess the safety, tolerability and immunogenicity of a Haemophilus influenzae type B (Hib) CRM197 conjugated vaccine administered to healthy infants at 2, 4, and 6 months of age.

The objective of this prospective clinical study was to evaluate the safety, tolerability and immunogenicity of Chiron Hib vaccine (Vaxem Hib) in Thai infants. This trial was conducted at Bhumibol Adulyadej Hospital, Bangkok, Thailand from June to November 1999. Three intramuscular injections of the vaccine were given to 119 infants at 2, 4 and 6 months of age. Reactions and adverse events after the vaccination were recorded. Blood samples for anti-PRP antibody were collected before the first immunization, and after the second and third immunizations. After the second dose, 91% and 58% of the subjects had anti-PRP antibody titers of > or =0.15 microg/ml and > or =1.0 microg/ml, respectively. After the third dose, 99% and 90% of the subjects had anti-PRP antibody titer > or =0.15 mcirog/ ml and > or =1.0 microg/ml, respectively. Local and systemic reactions were mild and transient. The study indicates that Vaxem Hib vaccine is safe and well tolerated. Three doses of the vaccine are necessary to achieve adequate protection in infants.

Rectal prolapse associated with cytomegalovirus pseudomembranous colitis in a child infected by human immunodeficiency virus.

We report a newly recognized presentation of cytomegalovirus (CMV) enterocolitis in a 4-year-old girl with newly diagnosed HIV disease who presented with rectal prolapse. Gross findings showed multiple whitish punctate lesions. An endoscopic examination revealed multiple shallow ulcers and pseudomembranes along the colon. A biopsy from colonic tissues demonstrated CMV-like inclusion bodies. A direct immunofluorescence assay using specific CMV monoclonal antibody was positive for CMV-infected cells in specimens from the rectal smear.

Efficacy and safety of meropenem as an empirical treatment for febrile neutropenia in children with cancer.

Meropenem is a promising carbapenem antibiotic as an empirical monotherapy in patients with febrile neutropenia (FN). With the limited data of the therapy in pediatric patients, the authors conducted this study to evaluate the efficacy and safety of meropenem as empirical antibiotic therapy in 30 pediatric cancer patients with FN (mean age = 7.5 years), who were admitted to King Chulalongkorn Memorial Hospital from May 2000 to December 2001. Meropenem 60 mg/kg/day was given intravenously every 8 hours. The efficacy of meropenem was assessed as successful, inconclusive and failure on days 3 and 5 of the therapy and compared to that of other empirical antibiotics used from January 1997 to April 2000. The study showed that six blood culture specimens (20%) grew organisms, half of which were considered to be contaminants, and six urine culture specimens (20%) grew gram negative rod bacteria. On day 3 and 5 of the therapy, the success rate of meropenem was higher than that of comparatives (30.0% vs 17.6% on day 3, 50.0% vs 39.3% on day 5). The use of meropenem appeared safe, with minimal side effects. In conclusion, the present study showed that meropenem was safe and tolerable in children. The efficacy as an empirical monotherapy in pediatric cancer patients with FN was satisfactory, with a failure rate of 23.3 per cent on day 5 of treatment.

Typhoid fever in children: experience in King Chulalongkorn Memorial Hospital.

Blood cultures of children treated at King Chulalongkorn Memorial Hospital from 1986 to 2000 were retrospectively reviewed and 19 specimens were positive for Salmonella typhi. Of 14 patients whose medical records were available, the age range was between 2 years and 15 years with a male to female ratio of 1.8:1. Major presentations were prolonged fever with a mean duration of 7 days and gastrointestinal manifestations including abdominal pain (71%), hepatomegaly (64%), anorexia (57%), vomiting (57%), and diarrhea (50%). Most cases had normal hematocrit values with white blood cell counts of 5,000-9,000 cells/mm3 and the percentage of neutrophils was 60-89. Complications were abnormal urine sediments (3) including a case of typhoid nephritis, severe enteritis (2) and acute hemolysis (1). Most isolates were susceptible to cotrimoxazole, ampicillin and ceftriaxone by the disk diffusion susceptibility test. Defervescence was seen within 3-14 days after antibiotic therapy. There was no mortality.

Hepatic dysfunction in dengue patients with various severity.

This prospective study was designed to evaluate the correlation between biochemical changes in hepatic function and severity of dengue infection in pediatric patients. One hundred and four children with a clinically and serologically confirmed diagnosis of dengue infection were classified into the non-shock group, i.e. 20 cases of dengue fever and 27 cases of dengue hemorrhagic fever, and the shock group comprising 57 cases of dengue shock syndrome. Liver function tests were performed within the first three days after defervescence or shock. The study showed that levels of aspartate transaminase and alanine transaminase were significantly higher, whereas, globulin level was significantly lower among patients with more severe disease (p < 0.05). Levels of albumin, alkaline phosphatase, bilirubin and prothrombin time were not different among the groups. In conclusion, hepatic dysfunction in dengue patients is a common condition. Patients with more severe disease have significantly higher transaminase and lower globulin levels.

Dengue infection: a global concern.

Dengue infection, one of the most important mosquito-borne viral diseases of humans, is now a significant problem in several tropical countries. The disease, caused by the four dengue virus serotypes, ranges from asymptomatic infection, undifferentiated fever, dengue fever (DF) to severe dengue hemorrhagic fever (DHF) with or without shock. DHF is characterized by fever, bleeding diathesis and a tendency to develop a potentially fatal shock syndrome. Hematological findings include vasculopathy, coagulopathy and thrombocytopenia as the most constant findings. During the last twenty-five years, there have been increasing reports of dengue infection with unusual manifestations, mainly with cerebral and hepatic symptoms. Laboratory diagnosis includes virus isolation, serology and detection of dengue ribonucleic acid. Successful treatment, which is mainly supportive, depends on early recognition of the disease and careful monitoring for shock. Prevention depends on control of the mosquito vector. More efforts must be made to understand the pathogenesis of DHF in order to develop a safe and effective dengue vaccine.

Clinical features of diphtheria in thai children: a historic perspective.

To study the clinical and laboratory features of childhood diphtheria, the cases of 381 children with clinical and bacteriological diagnoses of diphtheria who were treated at the Children's Hospital between 1976 and 1985 were reviewed. Of these, 191 were males and 190 were females. The mean age was 4.6 years. Approximately 75% of the patients had no history of immunization. Common manifestations of diphtheria included patch (100%), fever (92.4%), upper respiratory tract infection (91.6%), upper airway obstruction (42.3%), hoarseness (36.7%), and bull neck (11.3%). The mean duration of fever prior to admission was 3.3 days with a range of 0-11 days. Patch sites included the tonsils (91.9%), the pharynx (55.9%), the larynx (27.8%) and others (24.4%). Complications included upper airway obstruction (42.3%), cardiac complications (10.0%) and neurological complications (4.7%). The mortality rate was 5.8%. There were significant associations between death and the presence of bull neck, laryngeal patch, airway obstruction and cardiac complications. Early recognition and prompt treatment will decrease complications and mortality in this group of patients.

Endocarditis and pericarditis caused by Salmonella paratyphi A: two case reports and review of the literature.

We report on two children with paratyphoid fever and rare cardiac complications (endocarditis and pericarditis) during an outbreak of Salmonella paratyphi A infection in Bangkok, Thailand, in 1996. Both of the patients had underlying congenital heart disease. Two cases in the literatures of endocarditis and five cases of pericarditis caused by Salmonella paratyphi were reviewed. These rare cardiac complications should be considered among persons who reside in an endemic area of enteric fever or during disease outbreaks, especially in children with underlying heart diseases.

Antibody response to hepatitis B immunization in infants born to HIV-infected mothers.

OBJECTIVES: To determine the antibody response of hepatitis B immunization begun at birth in HIV-1 exposed infants. DESIGN: Prospective, clinical trial. SITE: King Chulalongkorn Memorial Hospital, Bangkok, Thailand. MATERIAL AND METHOD: Seventy six infants born to HIV-1 seropositive mothers, who were not hepatitis B carriers, received three 10 microgram doses of recombinant DNA hepatitis B vaccine (Engerix B, Smith Kline, Belgium) in a 0, 1 and 6 month schedule. The first dose was given at birth. Serum hepatitis B surface antibody (Anti -HBs) was measured at age 3, 9 and 12 months. Anti-HBs levels were determined by enzyme-linked immunoassay using the commercial kits (AUSAB EIA diagnostic kits, Abbott Laboratories, Chicago, USA) Antibody titer > or = 10 mIU/ml was defined as seroconversion. HIV infection was diagnosed by a positive test of HIV antibody at age > or = 18 months and/or by positive test of HIV polymerase chain reaction at age > or = 3 months. RESULTS: There were 14 HIV-1 infected (group 1) and 62 HIV-1 non infected (group 2) infants enrolled in this study. Anti-HBs titers of group 1 infants were significantly lower than those of groups 2 infants at both 3 and 6 months after the 3rd dose of vaccine, (Mann Whitney U test, p=0.019 and 0.001 respectively). Ten infants in group 1 and 57 infants in group 2 had anti-HBs titer > or = 10 mIU/ml. Their peak antibody titers were also noted at both 3 and 6 months after the 3rd dose of vaccine. Seroconversion rates were 71.4 per cent and 91.9 per cent in group 1 and 2 infants respectively, (p<0.05). Among the infants who had blood tests performed at age 12 months or 6 months after the 3rd dose of vaccine, anti-HBs titers declined in approximately 50 per cent of both groups of infants. There was a significantly higher percentage of seroconverters in group 1 who lost their protective titers than those in group 2, (p<0.001). CONCLUSION: The results in this study suggested that HIV-1 infected infants have poor antibody response to hepatitis B immunization and the protection was less durable. A fourth dose of vaccine at 6 months after the 3rd dose may be necessary.