Stuart Gan Memorial Lecture 2002. HIV/AIDS in children.

The incidence of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) in children has risen steadily over the years and has become an increasing cause of morbidity and mortality during childhood. More than 90% of all children with HIV infection acquired their infection at birth from HIV-infected mothers. With increasing evidence of heterosexual HIV transmission, the number of infected women and consequently their children is increasing. The transmission rate of HIV from mother to infant varies from 20% to 40%. Children can be affected directly through HIV infection and AIDS, and indirectly by the effects of their parents' HIV infection, including being orphaned, discrimination, infant abandonment and negative impact on children's education. Another concern regards children who are most vulnerable to HIV infection and AIDS, such as child prostitutes and children in difficult circumstances. Recommended actions include prevention of parental HIV infection, prevention of mother-to-child HIV transmission, addressing child prostitution, prevention of child labour and improving work conditions, assistance to street children, addressing discrimination, solving the problem of children orphaned by AIDS, reducing HIV-related child abandonment and creating new roles for schools in reducing negative social impact. Although the largest number of HIV-infected persons are from sub-Saharan Africa, the annual incidence of HIV infection in Asia is escalating alarmingly. As reported by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization in December 2001, HIV infection has already killed more than 20 million people worldwide since the beginning of the epidemic and has infected more than 40 million people; almost half of them were women. There are at least 7 million people living with HIV/AIDS in the Asia-Pacific region. The numbers of HIV-infected women and children are increasing at an alarming rate. Over 1 million children are HIV-infected; in the year 2000 alone, 600,000 children acquired HIV infection.

Seroprevalence of Epstein-Barr virus antibody among children in various age groups in Bangkok, Thailand.

There are no current data on previous Epstein-Barr virus (EBV) infections in different age groups of Thai children. This study was conducted to determine the prevalence of anti-EBV IgG antibody in healthy children of various age ranges in Bangkok, Thailand. Between June and December 1998, blood samples were collected from 425 volunteers aged 6 months to 15 years who attended a well baby clinic in the northern suburban part of Bangkok, Thailand. Serum samples were assayed for specific anti-EBV IgG antibodies using a commercial enzyme-linked immunosorbent assay kit. The percentage of children with positive anti-EBV IgG antibody increased with advancing age. The overall seropositivity rate was 72.7%. Children with anti-EBV IgG antibody were significantly older than those without the antibody. Seronegative children were reared at home significantly more frequently than seropositive children. These seroopidemiologic data will guide calculation of the appropriate age for administration of an EBV vaccine to children, when it becomes available.

Seroprevalence of Epstein-Barr virus infection in Thai children.

A hospital-based cross-sectional survey was conducted in Bhumibol Adulyadej Hospital, Bangkok, Thailand between January and December 1997 to study the seroprevalence of anti-EBV IgG antibody in previously healthy hospitalized children aged 0-15 years. Of 589 cases, there were 327 boys and 262 girls with a mean age of 3.9 years. The seroprevalence of EBV infection was 50.4, 72.8, 92.3, 96.6 and 97.6 per cent in children at the age range of 0-2, 3-5, 6-8, 9-11 and 12-14 years, respectively. After excluding infants below 6 months of age, the total seroprevalence rate was 68.4 per cent. The age of children with positive anti-EBV IgG antibody was significantly higher than that of children with negative antibody. Children who were reared at home had lower seroprevalence rates. In conclusion, seroprevalence of EBV infection increased with advancing age and reached 90 per cent or more after 6 years of age.

Neurological manifestations in dengue patients.

To determine the frequency and the natural history of neurological manifestations of dengue infection in Thai children, 1,493 children diagnosed with dengue infection by serology and admitted to the Department of Pediatrics, Chulalongkorn Hospital, Bangkok, Thailand from 1987 to 1998 were reviewed from prospectively recorded medical charts. There were 80 children identified with neurological manifestations, an incidence of 5.4% of all dengue patients. Of these, there were 41 males and 39 females, with ages ranging from 3 months to 14 years. They were categorized into 20 cases of dengue fever, 26 cases of dengue hemorrhagic fever and 34 cases of dengue shock syndrome. All cases experienced the neurological manifestations during the febrile stage of the illness. The patients were classified into an encephalitic group (called "dengue encephalopathy") (42), a seizure group (35) and a miscellaneous group (3). Encephalitic patients presented with alteration of consciousness (83.3%), seizure (45.2%), mental confusion (23.8%), nuchal rigidity (21.4%), spasticity of limbs (9.5%), positive clonus (4.8%), hemiplegia (2.4%) and positive kernig (2.4%), and were older than those in the other groups. Patients in the seizure group presented with seizure (100%) and positive clonus (2.9%). Abnormal laboratory findings included hyponatremia, abnormal liver enzymes and CSF pleocytosis. Dengue IgM and dengue PCR were not demonstrated in 16 CSF specimens. An autopsy finding of a child in the encephalitic group showed histologic evidence of encephalitis, the only case of confirmed dengue encephalitis in this study. One patient with encephalitic symptoms suffered from long-term neurological sequelae. The overall mortality rate was 5%. In conclusion, neurological manifestations including seizure and encephalopathy in children with dengue are not uncommon whereas dengue encephalitis is a rare entity.

Childhood cryptococcosis: an increasing problem in the era of AIDS.

The authors reported 8 children with cryptococcosis from King Chulalongkorn Memorial Hospital from 1991 to 2000. Five patients were older than five years. The two common underlying diseases were HIV/AIDS (5 cases) and systemic lupus erythematosus (2 cases). Seven cases had been observed in the past four years, four of these in 2000. One patient developed disseminated disease and two patients died. In the era of HIV/AIDS and due to the fact that HIV-infected children are tending to live longer, we may encounter a higher occurrence of this opportunistic fungus in children.

Measles-associated appendicitis: two case reports and literature review.

We report 2 cases of appendicitis associated with measles. Four previously reported cases are reviewed. In all 6 patients typical measles rash appeared after removal of the appendix, which showed Warthin-Finkelday giant cells.

Seroprevalence of anti-human herpes virus-6 IgG antibody in children of Bangkok, Thailand.

The prevalence of HHV-6 infection was surveyed by determining the presence of anti-human herpesvirus-6 IgG (Anti-HHV-6 IgG) using an ELISA method. Two hundred and ten sera collected from healthy Thai children aged between 0 to 12 years (mean +/- standard deviation = 3.35+/-3.33) indicated the prevalence of HHV-6 infection was 88.10% (185/210). Samples were classified into 7 groups, 30 samples each, according to their ages, ie, group 1: 0 - < 6 months; group 2: 6 - < 12 months; group 3: 12 - < 18 months; group 4; 18 - < 24 months; group 5: 2 - < 5 years; group 6: 5 - < 8 years and group 7: 8-12 years. The prevalence of HHV-6 infection was 63.33%, 70%, 96.67%, 93.33%, 100%, 100% and 93.33%, respectively. The mean level of anti-HHV-6 IgG among those positive for HHV-6 infection (185 samples) increased from 0 < 6 months old (17.47+/-6.32 units) to 27.57+/-8.42 units in 6 - < 12 months old, with the highest value found in the 18 - < 24 months old group (33.08+/-8.64 units). The level declined thereafter. A statistically significant difference of the mean level of anti-HHV-6 IgG among positive groups was found (p-value < 0.05). The important factor associated with HHV-6 infection was age (p = 0.002), while sex, socioeconomic status, number of children in the family and child rearing place did not show any association.

Failure of pre- and postexposure rabies vaccinations in a child infected with HIV.

We report the case of a 6-y-old HIV-infected girl with severe immune deficiency who failed to respond to intramuscular pre-exposure rabies vaccination using human diploid cell rabies vaccine on days 0, 7 and 28. She also failed to respond to an intradermal postexposure rabies regimen using purified verocell rabies vaccine at 4 sites on days 0, 3 and 7 and at 2 sites on days 30 and 90 (double the usual regimen). Sequentially monitored rabies neutralizing antibody titers were below the WHO minimum acceptable level (> 0.15 IU/ml) in all specimens. Rabies prevention in HIV-infected persons with severe immune suppression requires further study.

Immunologic and virologic evaluation of HIV-1-infected children after rabies vaccination.

BACKGROUND: One-third of Thai children experience a dog bite by the time they are 15 years old, and HIV-1 infection in children is also not uncommon. Previous study has shown that rabies vaccination of HIV-1-infected children may not result in a satisfactory antibody response when CD4+ T cells are less than 15%. The objective of this prospective clinical study is to evaluate the immunologic response and effect on viral load after rabies vaccination in HIV-infected children. METHODS: Thirteen HIV-1-infected children were vaccinated with the intramuscular rabies pre-exposure regimen using human diploid cell rabies vaccine (HDCV) on days 0, 7 and 28. CD4+ and CD8+ lymphocyte counts were performed on days 0, 7 and 28. Plasma viral loads were determined on days 0, 7, 14, 60, 90, 180 and 360. RESULTS: There were no significant change in serial measurements of CD4+/CD8+ lymphocytes during a period of 1 month and in plasma viral load during 1 year. There was no associated clinical deterioration or any adverse reactions attributable to vaccine. CONCLUSIONS: Rabies vaccination in HIV-1-infected children appears to be safe but did not significantly change the levels of plasma HIV RNA, CD4+ and CD8+ cell counts.

Primary dengue infection: what are the clinical distinctions from secondary infection?

To determine the magnitude of the problem posed by primary dengue infection in children and the distinctive clinical clues that may differ from those with secondary infection, 996 children serologically diagnosed with dengue infection and admitted to the Department of Pediatrics, Chulalongkorn Hospital, Bangkok, Thailand between 1988 and 1995 were retrospectively reviewed. One hundred and thirty-nine cases (14.0%) were serologically proved to be primary dengue infection. Of these, 72 were males and 67 were females, with a mean age of 4.8 years. Common manifestations by order of frequency included fever (97.8%), hepatomegaly (71.9%), vomiting (59.0%), decreased appetite (55.4%), coryza (52.5%), drowsiness (39.6%), diarrhea (34.5%), rash (33.8%), abdominal pain (23.0%) and seizure (15.8%). The mean duration of fever before admission was 4.6 days. Common sites of bleeding were skin (41.7%), mucous membrane (14.4%) and the gastrointestinal tract (12.2%). Clinical diagnosis was categorized into dengue fever (22.3%), dengue hemorrhagic fever (60.4%) and dengue shock syndrome (17.3%). Three patients (2.2%) died. Compared with the children with secondary dengue infection (n=139), children with primary dengue infections tended to be younger, presented more commonly with coryza, diarrhea, rash and seizure; and less commonly with vomiting, headache and abdominal pain (p < 0.05). The maximal hematocrit level, the mean difference between maximal and minimal hematocrit values and the maximal percentage of neutrophils were significantly lower in the study group, whereas the maximal percentage of lymphocytes was significantly higher. Dengue fever was more common and dengue shock syndrome was less common in the study group (p < 0.05). This study has emphasized that primary dengue infection is not uncommon and is less severe than secondary infection. Clinical presentations and laboratory findings are somewhat different between the two conditions.

Measles in Thai adults: three case reports and management of contact cases.

We report on three adults (one nurse and two medical students) diagnosed as having measles. All the patients presented with fever, cough, conjunctival injection and rash. They contracted measles from pediatric patients who had been treated at Chulalongkorn Hospital in the previous two weeks. Physical examination revealed Koplik's spots on the oral mucosa and typical maculopapular rash. The diagnosis was confirmed by viral isolation. Measles IgG antibodies were measured in 36 medical students who were in close contact with patient 2 and measles vaccines were given. Thirty-three specimens had positive measles IgG, two had equivocal results and one had negative result. The student with negative measles IgG eventually developed measles (patient 3). Except for patient 2 and 3, no further cases of measles were seen among the contacts.

Typhoid glomerulonephritis in a child: a rare complication of typhoid fever.

We report a child with typhoid glomerulonephritis who presented with fever, gastrointestinal symptoms, edema, hypertension and abnormal urine findings including microscopic hematuria and proteinuria. Salmonella typhi resistant to ampicillin and cotrimoxazole was isolated from a blood culture. Renal biopsy was not performed. The child successfully treated with ceftriaxone.

Seroprevalence of hepatitis A virus antibody among children and young adults in Bangkok.

OBJECTIVE: To determine the prevalence of hepatitis A virus (HAV) antibodies in various age groups of healthy children and young adults who have not received the hepatitis A vaccine. METHOD: Blood samples were collected from 825 volunteers aged 1-30 years from a well baby clinic and five academic institutions in the Don Mueang area from 1998 to 1999. Serum samples were assayed for specific HAV IgG antibodies using a commercial enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: The seropositivity rate (12.4% overall) in each age group was as follows: 1-3 years, 7.7 per cent; 4-7 years, 6.6 per cent; 8-11 years, 12.4 per cent; 12-15 years, 10.7 per cent and 16-30 years, 25.9 per cent. CONCLUSIONS: In the Don Mueang area of Bangkok, the majority of children (< 16 years) do not have natural immunity against HAV. The use of hepatitis A vaccine for this population should be considered. Pre-vaccination serologic screening for HAV IgG in children may not be worthwhile.

Rabies exposures in thai children.

OBJECTIVE: To determine the epidemiology of potential rabies exposures in Thai children. METHODS: The study was carried out at the Queen Saovabha Memorial Institute of the Thai Red Cross Society during I calendar year. All charts of victims aged 0 to 14 years with possible rabies exposures were retrospectively reviewed. RESULTS: Subjects were 2622 children, with a male to female ratio of 1.6:1 and a mean age of 6.7 years (range, 2 months to 14 years). Most exposures (86.3%) were related to dogs. The most common site of exposure was the lower extremity. The majority of exposures occurred in or around the home and as the consequence of unprovoked attacks rather than provoked attacks. Antirabies vaccines were given in all cases: 68.4% using the Thai Red Cross intradermal route, and 31.6% using the intramuscular route. Rabies immunoglobulin (RIG) was prescribed in 57.5% of children; 35.2% received human RIG (HRIG), and 22.3% received purified equine RIG (ERIG). CONCLUSIONS: This study confirms that rabies exposures, especially in children, are an important public health problem in Thailand. The reduced-dose, multiple-site intradermal rabies vaccine method and ERIG in place of HRIG reduce the cost of treatment.

Invasive pneumococcal infection and drug-resistant Streptococcus pneumoniae in Thai children.

Sixty-eight children with systemic Streptococcus pneumoniae infection were identified by hospital chart review between 1986-1997. The age distribution varied from 2 days to 15 years, with a mean age of 3.3 years. There were 35 boys and 33 girls. Four clinical entities included 30 cases of meningitis, 20 cases of pneumonia, 10 cases of peritonitis and 8 cases of septicemia/bacteremia. Forty patients (58.8%) had underlying diseases. Seventeen patients (25.0%) developed early complications and the mortality rate was 8.8 per cent. The percentage of susceptible isolates to penicillin, chloramphenicol, cefotaxime/ceftriaxone, ciprofloxacin, imipenem and vancomycin were 69.6, 91.3, 100.0, 87.2, 100.0 and 97.1 per cent, respectively. There were six cases of drug-resistant S. pneumoniae (DRSP) infection; 3 cases of meningitis, one case of pneumonia, one case of infective endocarditis and one case of purpura fulminans. Our data indicate that S. pneumoniae infection is relatively serious and life-threatening. There is a trend of increasing prevalence of invasive pneumococcal and DRSP infections.

A dengue shock patient with negative serology and polymerase chain reaction (PCR) tests.

A 6-month-old Thai girl presented with clinical manifestations of dengue shock syndrome (DSS) with encephalopathy and urinary tract infection. Serology and PCR tests were negative whereas dengue virus type 2 was isolated. In cases of highly suspected dengue infections, viral isolation should be done even when serological and PCR tests are negative.

Causes of fever in children with first febrile seizures: how common are human herpesvirus-6 and dengue virus infections?

This study was conducted to evaluate the etiologies of pyrexia in children with first febrile seizures using a prospectively recorded medical protocol, bacterial culture, and serologic tests for human herpesvirus-6 (HHV-6), dengue virus and Japanese B encephalitis (JE) virus. Of 82 children with first febrile seizures, who were between 3 months and 3 years old and had been admitted to Bhumibol Adulyadej Hospital between January 1997 and December 1998, 41 were boys and 41 were girls, with a mean age of 14.7 months. The average maximal body temperature was 39.7 degrees C. Approximately 70% of the children developed seizures on the first day of fever and the duration of the seizures varied from 1 to 30 minutes. In addition to fever and seizure, common symptoms and signs included coryza, diarrhea, vomiting, inflamed tympanic membranes and rash. The causes of fever documented upon discharge were, in order of frequency, upper respiratory tract infection, nonspecific febrile illness, diarrhea, urinary tract infection, viral infection, pneumonia, herpangina, measles, pneumococcal bacteremia and dengue fever. Serologic tests for HHV-6 IgM were positive in seven children (8.5%), and serologic tests for dengue and JE viruses were negative in all cases.

Epidemiology of invasive meningococcal disease in 13 government hospitals in Thailand, 1994-1999.

This study was conducted to elucidate the magnitude of problem and the clinical course of invasive meningococcal infection from 13 government hospitals in Thailand between 1994 and 1999. Thirty-six strains of Neisseria meningitidis were isolated from 16 blood and 24 cerebrospinal fluid specimens; 4 patients had positive culture in both blood and CSF. Of the 16 strains, 9 (56.3%) were serogroup B. Seventy-one and eighty-four percent of the isolates were susceptible to penicillin and cefotaxime/ceftriaxone respectively. Five out of six penicillin-nonsusceptible strains were found to be relatively resistant to penicillin with the MIC of 0.125 microg/ml. Of 33 patients whose medical records were available, 21 were males and 12 were females, with a mean age of 11.2 years. Fifteen patients (45.5%) presented with meningococcemia and 18 patients (54.5%) presented with meningococcal meningitis. Hypotension and purpura were found in 24.2% and 33.3% of patients respectively. The overall mortality rate was 9.1%. In conclusion, meningococcal disease is not common in Thailand, meningococcemia is a life-threatening condition whereas meningococcal meningitis is much less severe. The prevalence of meningococci relatively resistant to penicillin seems to be increasing.