Four-year safety follow-up of the tetravalent dengue vaccine efficacy randomized controlled trials in Asia and Latin America.

OBJECTIVE: Our objective was to describe the risk of hospital admission for virologically confirmed dengue (VCD) and the risk of clinically severe hospitalized VCD occurring up to 4 years after the first dose (years 1 to 4) in three randomized clinical trials comparing tetravalent dengue vaccine with placebo. METHODS: The relative risks (RR) for hospitalized VCD from first dose to year 4 were estimated by year and age-group in individual and combined studies. RESULTS: Overall, from Year 1 to Year 4, 233 and 228 participants had at least one episode of hospitalized VCD in the vaccinated (n = 22 603) and placebo (n = 11 301) groups, respectively (RR = 0.511, 95% CI 0.42-0.62). Among these, 48 and 47 cases, respectively, were classified as clinically severe. In children aged ≥9 years, 88 and 136 participants had at least one episode of hospitalized VCD in the vaccinated (n = 17 629) and placebo (n = 8821) groups, respectively (RR = 0.324; 95% CI 0.24-0.43). In vaccinated participants aged <9 years, particularly in those aged 2-5 years, there were more hospitalized VCD cases compared with the control participants in Year 3 but not in Year 4. The overall RR in those aged <9 years for Year 1 to Year 4 was 0.786 (95% CI 0.60-1.03), with a higher protective effect in the 6-8 year olds than in the 2-5 year olds. CONCLUSIONS: The overall benefit-risk remained positive in those aged ≥9 years up to year 4, although the protective effect was lower in years 3 and 4 than in years 1 and 2.

A comparison of pain scales in Thai children.

Three commonly used pain scales, the visual analogue scale, the Wong-Baker Faces Pain Scale, and the Faces Pain Scale Revised were administered to 122 Thai children, of whom half were HIV infected, in order to assess their validity. These scales presented moderate to good correlation and moderate agreement, sufficient for valid use in Thai children.

Intestinal microsporidiosis in HIV-infected children with acute and chronic diarrhea.

A prospective study of intestinal microsporidiosis in HIV-positive children was conducted at the Queen Sirikit National Institute of Child Health and Phramongkutklao Hospital, Bangkok, Thailand. Hospitalized HIV-positive children with and without diarrhea were enrolled in this study. Microsporidial spores identified by calcofluor fluorescent and gram-chromotrope stain were confirmed by electron microscopy. As well as Cryptosporidium parvum, Microsporidia was the most common protozoa found in the present study, each was 7.1%. Microsporidia was significantly more common in those who had diarrhea. Intestinal microsporidiosis was found in HIV-positive children with both acute and chronic diarrhea. This study emphasizes the importance of Microsporidia in HIV-infected children. Early detection of microsporidia could be of benefit for the patients, since the infection is treatable.

Safety of late in utero exposure to zidovudine in infants born to human immunodeficiency virus-infected mothers: Bangkok. Bangkok Collaborative Perinatal HIV Transmission Study Group.

BACKGROUND: Short-course zidovudine (ZDV) given in the late antenatal period can reduce mother-infant human immunodeficiency virus (HIV) transmission by one half. Because this intervention is being implemented in developing countries, evidence of its safety is needed. METHODS: In a randomized, double-blinded, placebo-controlled trial in Bangkok, HIV-infected pregnant women received either ZDV (300 mg twice daily from 36 weeks' gestation until labor, then every 3 hours until delivery) or an identical placebo regimen. Infants were evaluated at birth and at 1, 2, 4, 6, 9, 12, 15, and 18 months of age. Growth, clinical events, and hematologic and immunologic measurements were compared between treatment groups. RESULTS: Of the 395 children born (196 in ZDV group and 199 in placebo group), 330 were uninfected, 55 were infected, and 10 had indeterminate infection status. Overall, 319 children (81%) completed 18 months of follow-up, and 14 (4%) died before 18 months of age. Among uninfected children, the mean hematocrit was lower in the ZDV group at birth (49.1% vs 51.5%) but not at later ages; mean weight, height, head circumference, and CD4(+) and CD8(+) T lymphocyte counts were similar in both groups at all ages. Five uninfected children in the ZDV group but only one in the placebo group had a febrile convulsion. No other signs suggestive of mitochondrial dysfunction and no tumors were observed. Among infected children, an estimated 62% in the ZDV group and 77% in the placebo group survived free of Centers for Disease Control and Prevention class C disease during the 18-month follow-up. CONCLUSIONS: No significant adverse events were associated with short-course ZDV during 18 months of follow-up in this population.

Early diagnosis of HIV-1-infected infants in Thailand using RNA and DNA PCR assays sensitive to non-B subtypes.

OBJECTIVES: To evaluate the sensitivity and specificity of RNA and DNA polymerase chain reaction (PCR) for early diagnosis of perinatal HIV-1 infection and to investigate early viral dynamics in infected infants. DESIGN: A cohort study of 395 non-breastfed infants born to HIV-infected mothers in a randomized clinical trial of short-course antenatal zidovudine. METHODS: Infant venous blood specimens collected at birth, 2 months, and 6 months of age were tested by qualitative DNA and quantitative RNA PCR (Roche Amplicor). To determine sensitivity and specificity of DNA and RNA PCR, results were compared with later DNA PCR results and to antibody results at 18 months. The HIV-1 subtype of the mother's infection was determined by peptide serotyping. RESULTS: In the study, 92% of mothers were infected with subtype E. DNA PCR sensitivity was 38% (20 of 53) at birth, and 100% at 2 months (53 of 53) and 6 months (47 of 47). RNA PCR sensitivity was 47% (25 of 53) at birth and 100% (53 of 53) at 2 months. All samples that tested DNA-positive tested RNA-positive. Specificity was 100% for both DNA and RNA testing at all timepoints. For infected infants, the median viral load of RNA-positive specimens was 407,000 copies/ml (5.6 log10) at birth, 3, 700,000 copies/ml (6.6 log10) at 2 months, and 1,700,000 copies/ml (6.2 log10) at 6 months. Infant RNA levels at 2 and 6 months did not differ by maternal zidovudine exposure, or RNA level at birth. CONCLUSION: This RNA PCR assay performed well for diagnosing perinatal HIV subtype E infection, detecting nearly half of infected infants at birth, and 100% at 2 and 6 months, with 100% specificity. Infected infant viral RNA levels were very high at 2 and 6 months, and were unaffected by maternal zidovudine treatment.

Evaluating a new strategy for prophylaxis to prevent Pneumocystis carinii pneumonia in HIV-exposed infants in Thailand. Bangkok Collaborative Perinatal HIV Transmission Study Group.

OBJECTIVE: To evaluate a strategy for prophylaxis against Pneumocystis carinii pneumonia (PCP) for infants in Thailand. METHODS: HIV-infected women were offered trimethoprim-sulfamethoxazole for PCP prophylaxis for their children at 1-2 months of age. When the children reached 6 months of age, investigators simulated a decision to continue or stop prophylaxis on the basis of clinical criteria, and compared their decisions with results of polymerase chain reaction (PCR) testing for HIV. We calculated the proportions of children who received and completed prophylaxis, and compared the rates of pneumonia and death from pneumonia with rates from an earlier prospective cohort. RESULTS: Of 395 eligible infants, 383 (97%) started prophylaxis. By 6 months of age, 10 (2.6%) were lost to follow-up, three (0.8%) were non-adherent, seven (2%) had stopped because of adverse events, four (1%) had died, and 359 (94%) still received prophylaxis. At 6 months of age, 30 (70%) of 43 HIV-infected children and 16 (5%) of 316 uninfected children met the clinical criteria to continue prophylaxis. The incidence of pneumonia at 1 to 6 months of age was 22% (15/68) in the earlier cohort, and 13% (6/46) in the recent cohort [relative risk (RR) 0.6, 95% confidence interval (CI) 0.3-1.4; P= 0.22]; mortality rates were 9% and 4%, respectively (RR 0.5; 95% CI 0.1-2.3; P = 0.47). CONCLUSION: This PCP prophylaxis strategy appeared to be acceptable and safe, may have reduced morbidity and mortality from pneumonia, and should be considered in developing countries where early laboratory diagnosis of perinatal HIV infection is unavailable.

Elevated levels of maternal anti-tetanus toxin antibodies do not suppress the immune response to a Haemophilus influenzae type b polyribosylphosphate-tetanus toxoid conjugate vaccine.

Reported are the effects of elevated levels of anti-tetanus antibodies on the safety and immune response to a Haemophilus influenzae type b polyribosylphosphate (PRP)-tetanus toxoid conjugate (PRP-T) vaccine. A group of Thai infants (n = 177) born to women immunized against tetanus during pregnancy were vaccinated with either a combined diphtheria-tetanus-pertussis (DTP) PRP-T vaccine or DTP and a PRP-conjugate vaccine using Neisseria meningitidis group B outer-membrane proteins as a carrier (PedVax HIB). Although most infants possessed high titres (> 1 IU/ml) of anti-tetanus antibodies, the DTP-PRP-T combined vaccine engendered an excellent antibody response to all vaccine components. In both vaccine groups > 98% of infants attained anti-PRP antibody titres > or = 0.15 microgram/ml. The geometric mean anti-PRP antibody titres were 5.41 micrograms/ml and 2.1 micrograms/ml for infants immunized with three doses of PRP-T versus two doses of PedVax HIB vaccines, respectively (P < 0.005). Similarly, the proportion of infants who achieved titres > or = 1 microgram/ml was higher in the PRP-T group (87.8%) than in the group immunized with PedVax HIB (74.2%) (P = 0.036). A subgroup analysis showed that there was no significant difference in the anti-PRP antibody response for infants exhibiting either < 1 IU of anti-tetanus antibody per millilitre or > or = 1 IU/ml at baseline. These finding indicate that pre-existing anti-carrier antibody does not diminish the immune response to the PRP moiety. All infants possessed protective levels of anti-D and anti-T antibody levels after immunization.

PIP: Reported are the effects of elevated levels of anti-tetanus antibodies on the safety and immune response to Haemophilus influenzae type b polyribosylphosphate (PRP)-tetanus toxoid conjugate (PRP-T) vaccine. A group of Thai infants (n = 177) born to women immunized against tetanus during pregnancy were vaccinated with either a combined diptheria-tetanus-pertussis (DTP) PRP-T vaccine or DTP and a PRP-conjugate vaccine using Neisseria meningitidis group B outer-membrane proteins as a carrier (PedVax HIB). Although most infants possessed high titers (1 IU/ml) of anti-tetanus antibodies, the DTP-PRP-T combined vaccine engendered an excellent antibody response to all vaccine components. In both vaccine groups, 98% of infants attained anti-PRP antibody titers of 0.15 mcg/ml or higher. The geometric mean anti-PRP antibody titers were 5.41 mcg/ml and 2.1 mcg/ml for infants immunized with 3 doses of PRP-T vs. 2 doses of PedVax HIB vaccines, respectively (P 0.005). Similarly, the proportion of infants who achieved titers of 1 mcg/ml or higher was greater in the PRP-T group (87.8%) than in the group immunized with PedVax HIB (74.2%) (P = 0.036). A group analysis showed that there was no significant difference in the anti-PRP antibody response for infants exhibiting either less than 1 IU/ml of anti-tetanus antibody or 1 or more IU/ml at baseline. These findings indicate that pre-existing anti-carrier antibody does not diminish the immune response to the PRP moiety. All infants possessed protective levels of anti-D and anti-T levels after immunization.

Short-course zidovudine for perinatal HIV-1 transmission in Bangkok, Thailand: a randomised controlled trial. Bangkok Collaborative Perinatal HIV Transmission Study Group.

BACKGROUND: Many developing countries have not implemented the AIDS Clinical Trials Group 076 zidovudine regimen for prevention of perinatal HIV-1 transmission because of its complexity and cost. We investigated the safety and efficacy of short-course oral zidovudine administered during late pregnancy and labour. METHODS: In a randomised, double-blind, placebo-controlled trial, HIV-1-infected pregnant women at two Bangkok hospitals were randomly assigned placebo or one zidovudine 300 mg tablet twice daily from 36 weeks' gestation and every 3 h from onset of labour until delivery. Mothers were given infant formula and asked not to breastfeed. The main endpoint was babies' HIV-1-infection status, tested with HIV-1-DNA PCR at birth, 2 months, and 6 months. We measured maternal plasma viral concentrations by RNA PCR. FINDINGS: Between May, 1996, and December, 1997, 397 women were randomised; 393 gave birth to 395 live-born babies. Median duration of antenatal treatment was 25 days, and median number of doses during labour was three. 99% of women took at least 90% of scheduled antenatal doses. Adverse events were similar in the study groups. Of 392 babies with at least one PCR test, 55 tested positive: 18 in the zidovudine group and 37 in the placebo group. The estimated transmission risks were 9.4% (95% CI 5.2-13.5) on zidovudine and 18.9% (13.2-24.2) on placebo (p=0.006; efficacy 50.1% [15.4-70.6]). Between enrolment and delivery, women in the zidovudine group had a mean decrease in viral load of 0.56 log. About 80% of the treatment effect was explained by lowered maternal viral concentrations at delivery. INTERPRETATION: A short course of twice-daily oral zidovudine was safe and well tolerated and, in the absence of breastfeeding, can lessen the risk for mother-to-child HIV-1 transmission by half. This regimen could prevent many HIV-1 infections during late pregnancy and labour in less-developed countries unable to implement the full 076 regimen.

Maternal viral load and timing of mother-to-child HIV transmission, Bangkok, Thailand. Bangkok Collaborative Perinatal HIV Transmission Study Group.

OBJECTIVES: To determine the proportion of HIV-1-infected infants infected in utero and intrapartum, the relationship between transmission risk factors and time of transmission, and the population-attributable fractions for maternal viral load. DESIGN: Prospective cohort study of 218 formula-fed infants of HIV-1-infected untreated mothers with known infection outcome and a birth HIV-1-positive DNA PCR test result. METHODS: Transmission in utero was presumed to have occurred if the birth sample (within 72 h of birth) was HIV-1-positive by PCR; intrapartum transmission was presumed if the birth sample tested negative and a later sample was HIV-1-positive. Two comparisons were carried out for selected risk factors for mother-to-child transmission: infants infected in utero versus all infants with a HIV-1-negative birth PCR test result, and infants infected intrapartum versus uninfected infants. RESULTS: Of 49 infected infants with an HIV-1 birth PCR result, 12 (24.5%) [95% confidence interval (CI), 14 -38] were presumed to have been infected in utero and 37 (75.5%) were presumed to have been infected intrapartum. The estimated absolute overall transmission rate was 22.5%; this comprised 5.5% (95% CI, 3-9) in utero transmission and 18% (95% CI, 13-24) intrapartum transmission. Intrapartum transmission accounted for 75.5% of infections. High maternal HIV-1 viral load (> median) was a strong risk factor for both in utero [adjusted odds ratio (AOR) 5.8 (95% CI, 1.4-38.8] and intrapartum transmission (AOR, 4.4; 95% CI, 1.9-11.2). Low birth-weight was associated with in utero transmission, whereas low maternal natural killer cell and CD4(+) T-lymphocyte percentages were associated with intrapartum transmission. The population-attributable fraction for intrapartum transmission associated with viral load > 10 000 copies/ml was 69%. CONCLUSIONS: Our results provide further evidence that most perinatal HIV-1 transmission occurs during labor and delivery, and that risk factors may differ according to time of transmission. Interventions to reduce maternal viral load should be effective in reducing both in utero and intrapartum transmission.

Maternal virus load and perinatal human immunodeficiency virus type 1 subtype E transmission, Thailand. Bangkok Collaborative Perinatal HIV Transmission Study Group.

To determine the rate and risk factors for human immunodeficiency virus (HIV)-1 subtype E perinatal transmission, with focus on virus load, pregnant HIV-infected women and their formula-fed infants were followed prospectively in Bangkok. Of 281 infants with known outcome, 68 were infected (transmission rate, 24.2%; 95% confidence interval, 19.3%-29.6%). Transmitting mothers had a 4.3-fold higher median plasma HIV RNA level at delivery than did nontransmitters (P<.001). No transmission occurred at <2000 copies/mL. On multivariate analysis, prematurity (adjusted odds ratio [AOR], 4.5), vaginal delivery (AOR, 2.9), low NK cell percentage (AOR, 2.4), and maternal virus load were associated with transmission. As RNA quintiles increased, the AOR for transmission increased linearly from 4.5 to 24.8. Two-thirds of transmission was attributed to virus load>10,000 copies/mL. Although risk is multifactorial, high maternal virus load at delivery strongly predicts transmission. This may have important implications for interventions designed to reduce perinatal transmission.

AIDS in ENT in children.

Human immunodeficiency virus (HIV) infection is one of the most widespread diseases in the world. By the end of 1995, 800,000 HIV infected persons were suspected in Thailand, although the reported number of symptomatic HIV patients was only 13,267 and the number of cases of acquired immunodeficiency syndrome (AIDS) was 31,439. Approximately 5.2% of AIDS patients are cases of paediatric AIDS, contracted mostly by perinatal transmission and with a 25% vertical transmission rate. In a study of paediatric AIDS patients in the Children's Hospital, Thailand, from 1992 to 1995, the five most common clinical manifestations were hepatosplenomegaly (82.85%), persistent pneumonia (64.4%), oral candidiasis (59.6%), chronic diarrhoea (58.4%) and failure to thrive (51.2%). In addition to oral candidiasis, other ENT (ear nose-throat) presentations were lymphadenopathy (41.6%), repeated upper respiratory tract infection (39.5%), otitis media (18.4%), parotitis (5.2%) and sinusitis (0.8%).

HIV prevalence, risk, and partner serodiscordance among pregnant women in Bangkok. Bangkok Collaborative Perinatal HIV Transmission Study Group.

CONTEXT: Most prior studies of the human immunodeficiency virus (HIV) epidemic in Thailand have focused on commercial sex encounters; however, because the epidemic increasingly concerns stable heterosexual relationships, determining risk factors for this form of transmission is warranted. OBJECTIVES: To determine temporal trends in HIV prevalence, risk factors for HIV seropositivity, and rates of partner serodiscordance for pregnant women in Bangkok, Thailand. DESIGN: Retrospective review of hospital antenatal clinic HIV test results from 1991 through 1996. Baseline demographic and behavioral risk factors for HIV were assessed for subjects enrolled from November 1992 through March 1994. SETTING: Two Bangkok hospitals with routine antenatal clinic HIV counseling and testing. PARTICIPANTS: The HIV-positive pregnant women enrolled in a perinatal HIV transmission study and their partners and HIV-negative pregnant controls. RESULTS: From 1991 through 1996, antenatal clinic HIV seroprevalence increased from 1.0% to 2.3%. On multivariate analysis of data from 342 HIV-positive and 344 HIV-negative pregnant women, more than 1 lifetime sex partner, history of a sexually transmitted disease, and a high-risk sex partner were the most important factors for seropositivity (all P<.001). Twenty-six percent of partners of HIV-positive women were HIV negative. Women reporting more than 1 lifetime sex partner were more likely to have an HIV-negative partner than women reporting only 1 (45% vs 8%; relative risk, 5.5; 95% confidence interval, 3.2-9.5; P<.001); women reporting no high-risk behaviors were less likely to have an HIV-negative partner (10% vs 44%; relative risk, 0.2; 95% confidence interval, 0.1-0.4; P<.001). CONCLUSIONS: Prevalence of HIV in pregnant women has increased steadily in Bangkok from 1991 through 1996. Sex with current partners was the only identified risk exposure for about half (52%) of the HIV-positive women. Although few HIV-positive pregnant women reported high-risk behaviors, more than 1 lifetime partner and a partner with high-risk behavior were strong risk factors for seropositivity. Together with the unexpected finding that one fourth of partners of seropositive pregnant women were seronegative, these data emphasize that women in the general population are at risk for HIV because of the risk behavior of both current and previous partners.

Knowledge, attitudes, and practices of senior high school students regarding human immunodeficiency virus infection.

A survey of knowledge, attitude and practice (KAP) regarding human immunodeficiency virus infection was performed on 899 students from 3 government-administered high schools located in the Bangkok Metropolitan area. Initially, all students completed a written questionnaire (pre-test) regarding HIV/AIDS. Following this, they attended a slide lecture presentation given by a specialist physician. The same test questionnaire was then completed by the same students six weeks (post-test) later for comparison of their previous KAP. The subjects composed of male to female ratio equal to that of the median age 15-16 years old. Sixty-seven per cent of the subjects were living with their parents, 16.3 per cent with relatives and 15 per cent with friends. Ninety nine per cent of the subjects had received information on HIV/AIDS before enrollment to this study. The source of knowledge ranged from television (89.1%), teachers (81.6%), pamphlets (80.2%), newspapers (75%), radio (55%), health care workers (53.4%), friends (38.6%) and only 32.5 per cent from their parents. The subjects' knowledge about HIV/AIDS and risk factors in the post-test questionnaire was significantly increased (P < 0.001) from the pre-test status. However, their attitudes to an HIV infected person were not significantly changed in the post-test questionnaire: only the "attending school" question showed significantly (P < 0.05) increased numbers of agreement. Similarly, the attitudes and practices to prevent HIV infection were not significantly (P > 0.05) different between pre-test and post-test questionnaires. The result of this study is to recommend regular school-based programs of education to increase awareness of preventive strategies for HIV/AIDS and sexually transmitted diseases.

Response to JE vaccine among HIV-infected children, Bangkok, Thailand.

Since 1990, Japanese encephalitis (JE) vaccine has been part of EPI in northern Thailand, where there is a high prevalence of JE and HIV infection. To evaluate the immunogenicity and safety of JE vaccine among HIV-infected children, we conducted a retrospective study of HIV-infected and uninfected children who received 2 doses of JE vaccine at 12 months of age. Pre- and post-immunization plasma specimens were tested by plaque reduction neutralization for antibody levels to JE and dengue(1-4) viruses; titers of > or =10 were considered positive. Excluding 5 children with preimmunization antibodies, 5 of 14 (36%) HIV-infected children and 18 of 27 (67%) uninfected children had positive JE antibody titers after immunization [odds ratio (OR) 0.3, p=0.06]; 31% absolute difference [95% confidence interval (CI) 0-61.7%). The geometric mean titer of HIV-infected children with positive titers was lower than that of control children (15.1 vs, 23.8; p=0.17). No significant vaccine-associated adverse events were noted. We conclude that primary antibody response to JE vaccine was low among HIV-infected children and was approximately half of that seen among uninfected children. In endemic areas, HIV-infected children are likely to be at risk of acquiring JE despite routine immunization with 2 doses.

Chlamydial and gonococcal cervicitis in HIV-seropositive and HIV-seronegative pregnant women in Bangkok: prevalence, risk factors, and relation to perinatal HIV transmission.

OBJECTIVES: To determine the prevalence and risk factors associated with cervicitis caused by Chlamydia trachomatis and Neisseria gonorrhoeae in human immunodeficiency virus (HIV) type 1-seropositive and HIV-seronegative pregnant women in Bangkok, and the relation to perinatal HIV transmission. METHODS: As part of a multicenter perinatal HIV transmission study in an antenatal population with 2% HIV seroprevalence, endocervical swabs obtained at mid-pregnancy from a consecutive sample of 222 HIV-seropositive and 219 HIV-seronegative pregnant women at two large hospitals in Bangkok were tested for the presence of C. trachomatis and N. gonorrhoeae by DNA hybridization probe (Gen-Probe). Clinical risk factors and DNA probe results were analyzed in relation to the women's and newborns' HIV infection status. RESULTS: The prevalence of C. trachomatis was 16.2% in HIV-seropositive pregnant women and 9.1% in HIV-seronegative pregnant women (P = 0.03). The prevalence of N. gonorrhoeae was 2.7% in HIV-seropositive pregnant women and 1.4% in HIV-seronegative pregnant women (P = 0.5). The overall population prevalence estimate was 9.2% for C. trachomatis and 1.4% for N. gonorrhoeae. Women with gonococcal infection were more likely to be positive for C. trachomatis (RR(MH) = 5.2, P < 0.01). Young age (<21 years) and primigravid status were associated with C. trachomatis infection among HIV-seropositive women; history of multiple sex partners (>1) were associated with C. trachomatis infection among HIV-seronegative women. For HIV-seropositive women, primigravida status also was associated with C. trachomatis infection. The perinatal HIV transmission rates were similar for those with and without C. trachomatis (24.1% and 23.2%, P = 0.9) and among those with and without N. gonorrhoeae (20% and 23.5%, P = 1.0). CONCLUSIONS: Among pregnant women in Bangkok, C. trachomatis infection was considerably more common than N. gonorrhoeae infection and was associated with HIV infection, young age and first pregnancy (HIV-seropositive women), and multiple partners (HIV-seronegative women). Our data do not suggest an association between perinatal HIV transmission and maternal C. trachomatis or N. gonorrhoeae infection identified and treated during pregnancy. The high prevalence of C. trachomatis found using a test not readily available in Thailand emphasizes the need for improved, inexpensive ways to screen for and diagnose these sexually transmitted infections in developing countries.

PIP: Numerous studies have suggested that Chlamydia trachomatis and Neisseria gonorrhoeae facilitate heterosexual HIV transmission; the impact of these sexually transmitted diseases (STDs) on perinatal HIV transmission is unknown, however, due to the expense of routine screening for STDs during pregnancy in developing countries. As part of a multicenter perinatal HIV transmission study, 222 HIV-positive and 219 HIV-negative women presenting for prenatal care at 2 hospitals in Bangkok, Thailand, during 1993-94 were enrolled. At mid-pregnancy, endocervical swabs were obtained and tested for the presence of C. trachomatis and N. gonorrhoeae by DNA hybridization probe. There were 36 cases (16.2%) of C. trachomatis infection among HIV-positive women and 20 cases (9.1%) among HIV-negative women. There were 6 cases (2.7%) of N. gonorrhoeae among HIV-positive women and 3 cases (1.4%) among HIV-negative women. Based on an estimated antenatal HIV seroprevalence of 2%, these findings imply a general antenatal prevalence of 9.2% for C. trachomatis and 1.4% for N. gonorrhoeae. Women with gonococcal infection were more likely (relative risk, 5.2) to be positive for C. trachomatis as well. C. trachomatis infection among HIV-infected pregnant women was associated with age under 21 years and primigravidity. The overall perinatal HIV transmission rate was 24.2%, with no significant difference according to STD infection status. However, since all women diagnosed with STDs received treatment by the mid-third trimester of pregnancy, it remains possible that untreated STDs facilitate perinatal HIV transmission. The high prevalence of C. trachomatis detected in this study through use of a test not readily available in Thailand emphasizes the need for inexpensive, reliable methods to screen for STDs among pregnant women in developing countries.

Safety and immunogenicity of a Haemophilus influenzae type B polysaccharide-tetanus toxoid conjugate vaccine combined with diphtheria, tetanus and pertussis vaccines in Thai infants.

A randomized, open, multicenter trial was conducted to determine the safety and immunogenicity of a Haemophilus influenzae type b polysaccharide-tetanus toxoid (PRP-T) conjugate vaccine combined with tetanus, diphtheria and pertussis (DTP) vaccine in 271 Thai infants born to mothers immunized against tetanus during pregnancy. Infants were immunized at approximately 2, 4 and 6 months of age with these vaccines. To determine if elevated levels of anti-tetanus toxin antibodies suppressed the anti-PRP antibody response, a second group of infants were immunized with PRP complexed with outer membrane proteins of Neisseria meningitidis (Pedvax HIB) in one limb at 2 and 4 months of age and DTP vaccine in the other limb at 2, 4 and 6 months of age. A third group of infants received only DTP vaccine at 2, 4 and 6 months of age. The occurrence of both local and systemic adverse reactions were comparable in all 3 groups. The geometric mean anti-tetanus antibody titer was > 1 IU/ml at baseline. Approximately 1 month after the administration of the third dose of vaccine, 98.5%, 99.3% and 9.7% of the children immunized with DTP+Pedvax HIB, DTP-PRP-T or DTP possessed > or = 0.15 microgram of anti-PRP antibody per ml. No child in the DTP group achieved > or = 1 microgram/ml while 74.2% and 89.3% did so after immunization with DTP+Pedvax HIB, or DTP-PRP-T, respectively (p < 0.05). Immune responses to diphtheria, tetanus and pertussis antigens were similar in all vaccine groups. These results demonstrate that elevated tetanus antibody titers do not diminish the anti-PRP antibody response following immunization with a PRP-T conjugate combined with DTP vaccine.

Early diagnosis of vertical HIV infection in infants by rapid detection of immune complex-dissociated HIV p24 antigen.

Conventional HIV antibody detection was problematic for diagnosis of HIV infection in young infants < 18 months of age who were born to HIV-infected mothers. The HIV p24 antigen (Ag) is mainly bound to the antibody as an immune complex which causes underdetection by conventional methods. Attempts were made to dissociate these immune complexes to release free p24 Ag for detection. The current study's objective was to evaluate the rapid assays for detection of immune complex-dissociated p24 Ag (ICD p24 Ag) for early identification of HIV-infected infants as compared to the detection of HIV RNA by polymerase chain reaction (PCR) assay. The ICD was performed by acid dissociation and heat-denatured dissociation, and then the released ICD p24 Ag were detected. Tested were 41 HIV-infected children who acquired the infection perinatally and who had positive PCR and 30 HIV noninfected children with negative PCR. The overall sensitivity of the ICD p24 Ag detection after acid- and heat-denatured dissociation in the infected children was 85.4% and 87.8%, respectively, compared to 34.2% of p24 Ag without pretreatment for dissociation of the serum samples. The specificity of nonimmune complex dissociation and both methods of immune complex dissociation test were 100%. The sensitivity of ICD-p24 Ag test using these two methods showed excellent agreement (K = 0.893). Besides the relatively high sensitivity and specificity of the ICD p24 Ag test, its advantages include simplicity, rapidity, and relatively low cost--indicating ICD p24 Ag detection as a promising method for early diagnosis of vertical HIV infection in infants.

Perinatal HIV infections in Thailand.

A collaborative study group of researchers from seven hospitals from all regions of Thailand was formed to collect information on children born to HIV-infected mothers since the beginning of the first hospital case until the end of June 1994. The study conducted to verify the status of perinatal transmission of HIV infection in Thailand showed a rapid increase in HIV seropositivity among Thai mothers with vertical transmission rates varying between 25% in Rayong and 42% in Chiang Rai Hospitals, respectively. The majority of children with symptomatic HIV infection had clinical presentations of delayed growth development, pneumonia, diarrhea, oral candidiasis, lymphadenopathy, hepato-splenomegaly. Cases of Penicillium marneffei infection were found only at Chiang Rai Prachanukroh Hospital. The ages at which diagnosis of HIV disease was made were mostly within the first year of life. One third of children with AIDS died during the period of study.