Longitudinal studies of children born to HIV-1 antibody positive Filipino commercial sex workers (CSW): diagnostic dilemmas.

Fifteen term babies born to 12 HIV-1 antibody positive Filipino CSW have been monitored for signs and symptoms of HIV-1 infection. Eleven babies were enrolled in the study within the first 6 months after birth; 4 others were enrolled at 4, 9, 11 and 21 months of age respectively. Every 3 months after enrolment, each baby received a physical examination, serum was tested for HIV-1 antibodies and p24 antigen and peripheral blood mononuclear cells were cultured for isolation of virus. After a mean follow-up period of 39.3 months (range 7-72 months), virus isolation and serum p24 antigen assays confirmed that 2 babies have been infected with HIV-1. If the 4 babies less than 18 months of age were excluded, the vertical transmission rate was 18.2%. Seven babies who have been monitored for a minimum of 25 months (range 31-60 months) lost their maternal antibodies but 6 of them subsequently developed indeterminant Western blots (WB); reactivity to p24 and/or gp120/ 160 but no reactivity to gp41. Of the remaining 6 babies, still less than 25 months of age (range 7-24 months), 2 lost their maternal antibodies within one year. The other 4 continued to recognize either p24 or gp120/160 well after the accepted 15-month period for loss of maternal antibody. Although a diagnosis could not be established upon the basis of these laboratory findings, clinical observations (failure to thrive, anergy, persistent generalized lymphadenopathy and recurrent pneumonias) mimicked HIV-1 infection. However, because these clinical features are common among many babies in the developing world, their usefulness in supporting a diagnosis of perinatal HIV-1 infection is limited.

PIP: Clinicians monitored 15 full-term infants born to 12 HIV-1 seropositive commercial sex workers in the Philippines for signs and symptoms of HIV-1 infection. They performed a physical examination and HIV test on each infant every 3 months. The mean follow-up period was 39.3 months (range 7-72 months). Two infants tested positive for HIV-1 infection. When the researchers excluded the four infants under 18 months of age, the HIV-1 perinatal transmission rate stood at 18.2%. The maternal antibodies in seven infants who were monitored for at least 25 months disappeared; yet six subsequently developed indeterminant Western blots (i.e., reactivity to p24 and/or gp120/160, but no reactivity to gp41). The maternal antibodies in two of the six remaining infants who were under 25 months old disappeared within 1 year. The Western blots still recognized either p24 or gp120/160 in the other four infants beyond the accepted 15-month period for loss of maternal antibody. The clinicians could not establish a diagnosis based on these laboratory findings. They did diagnose signs and symptoms that may indicate HIV-1 infection (i.e., failure to thrive, anergy, persistent generalized lymphadenopathy, and recurrent pneumonias). Yet these clinical features are prevalent in many infants in developing countries, thereby making their usefulness in diagnosing perinatal HIV-1 infection limited.

A non-invasive assessment of hepatitis B virus carrier status using saliva samples.

A non-invasive testing method to determine hepatitis B virus (HBV) carrier status in pregnant women was evaluated. Paired serum and saliva samples were collected and assessment of hepatitis B markers were performed. Of the 502 women enrolled, 5.6% (28/502) of their sera were found to be positive for HBV surface antigen (HBsAg). Assessment of 28 HBsAg seroreactive and 200 HBsAg sero-non-reactive paired saliva samples showed that 17 saliva contained HBsAg. Fourteen of the saliva reactive samples were matched to the serum reactive samples (50% sensitivity); and 3 saliva samples were positive for HBsAg among 200 subjects seronegative for HBsAg (98.5% specificity). Seven of the 28 HBsAg positive sera were found to be reactive for HBV envelope antigen (HBeAg) (25%). One of seven HBeAg seroreactive and 16 HBeAg seronegative paired saliva samples tested were non-reactive for HBeAg. This report found a non-invasive saliva testing method to be a possible alternative approach for determining chronic HBV carrier status if the sensitivity of the test can be improved.

Natural history of HIV infection in Filipino female commercial sex workers.

A prospective follow-up study of the progression of HIV infection, from seroconversion to onset of opportunistic infections (OI) indicative of immune deficiency and to death, was performed in a cohort of 54 HIV-1 antibody positive Filipino female commercial sex workers (FCSW). The cumulative probability of having a CD4+ T cell count of < 200/mm3 and/or an OI indicative of severe immune deficiency was 52.9% within 5 years and 73.8% within 6 years after seroconversion. The cumulative probability of death was 52.1% within 6.5 years following seroconversion and 52.7% within 1.5 years after a depressed (< 200/mm3) CD4+ T cell or onset of an OI. Although several OI associated with immune impairment were observed, a CD4+ cell count of < 200/mm3 was the initial indicator of a failing immune system in more than 50% of the patients. Mycobacterium tuberculosis or unidentified acid fast bacilli (presumed to be M. tuberculosis) and Pneumocystis carinii pneumonia were the initial indicators of immune deficiency in the remaining patients.

Isolation of HIV-1 from Filipino commercial sex workers (CSWs).

Peripheral blood mononuclear cells (PBMC) from 36 HIV-1 antibody positive Filipino female commercial sex workers (CSWs) were co-cultivated at a 1:1 ratio with phytohemagglutinin-P activated PBMC from healthy, HIV-1 antibody negative donors. After 3-18 (mean 7.2) days of incubation at 37 degrees C in 5% CO2, 29 cultures showed evidence of replication of HIV-1: increasing concentrations of p24 antigen in the growth medium and the appearance of multinucleated giant cells. Although the length of incubation required for the appearance of cytopathogenic effect for each particular isolate was essentially the same when either 6 microwell plates were seeded with 3.0 x 10(6) cells/well or 24 well plates were seeded with 1.5 x 10(6) cells/well, the 24 well format was more sensitive. The ability to isolate HIV-1 from PBMC did not appear to be associated with the progression of disease or the presence or absence of any specific clinical findings. However, if the PBMC were from individuals with a concomitant p24 antigenemia, the incubation time required for isolation was significantly shorter (mean 3.8 days). The absolute CD4+ lymphocyte count was also slightly reduced in the culture positive, p24 antigenemic patients (range 302-813 cells/mm3, mean 502 cells/mm3) compared to the culture positive, p24 serum negative cases (range 311-1,511 cells/mm3, mean 830 cells/mm3). The p24 serum negative cases with CD4+ counts of < 500 cells/mm3 had positive PBMC cultures by 6 days of incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Outbreak of fatal illness among captive macaques in the Philippines caused by an Ebola-related filovirus.

Following the detection of an Ebola-like virus in cynomolgus macaques recently imported into the United States from The Philippines, studies were initiated to document transmission at export facilities located in the latter country. At one export facility, 52.8% of 161 monkeys that died over a 2.5-month period were shown to be infected with this virus using an enzyme-linked immunosorbent assay to detect antigen in liver homogenates. A case fatality rate of 82.4% was documented for the infected monkeys. The initial anti-viral antibody prevalence among the captive macaques at this facility was 25.9% (indirect fluorescent antibody titer greater than or equal to 1:16). Followup documented infection of 24.4% of initially seronegative animals and 8.7% of initially seropositive monkeys. Being held in a gang cage versus a single cage was found to be a significant risk factor for subsequent virus infection, and the presence of IFA antibody was shown to predict protection. This study documents unequivocally for the first time the presence of an Ebola-related filovirus in Asia.

HIV-1 seropositive women in the Philippines: pregnancy outcome and perinatal transmission of HIV-1.

Annual surveillance studies were initiated in 1985 to determine the incidence and prevalence of HIV-1 infection in female prostitutes registered through the Social Hygiene Clinic System of the Philippine Department of Health. All of the confirmed HIV-1 seropositive women detected in the above surveys who could be contacted were followed up about every three months to monitor their clinical and immunological status. Since we regularly interviewed and examined these HIV-1 seropositive women, we were able to note the occurrence of pregnancies following HIV diagnosis. By September 1990, 54 HIV-1 seropositive women (aged 18-35) detected from the above surveys had been interviewed and examined. Twenty-six of these HIV-1 positive women had a total of 37 pregnancies. Eight were pregnant at the time of HIV diagnosis: three term deliveries, one premature delivery (PD) at eight months, three abortions, and one lost to follow-up while still pregnant. Five of these eight had repeat pregnancies: two term deliveries, two abortions, and one lost to follow-up while pregnant. Eighteen other women became pregnant one or more times after HIV diagnosis: seven term deliveries, 13 abortions, two PDs, one ectopic pregnancy terminated, one currently pregnant, and one lost to follow-up during pregnancy. There was no clear indication from clinical examinations and CD4+ cell counts that pregnancy exacerbated the course of HIV-1 related disease in these women. One of the 12 term infants has died and eight have developed non-specific findings that are suggestive but not diagnostic of HIV infection.2+ strongly seropositive by both ELISA and Western blot assay at 16 months.

Sexual behavior of Filipino female prostitutes after diagnosis of HIV infection.

A study of female prostitutes in Manila who tested positive for human immunodeficiency virus (HIV) antibody ascertained demographic and sexual behavior information following diagnosis. Counselling alone did not appear to have a major impact on the sexual behavior of the HIV positive women since most continued to work as prostitutes. Switching from high risk to low risk jobs in bars is not effective in preventing HIV positive women from engaging in prostitution. Revoking work permits is only effective if enforced with adequate follow up. Alternative job training programs may offer a viable approach.

Epidemiology of HIV infection among prostitutes in the Philippines.

Between 1985 and 1987, examinations for human immune deficiency virus (HIV) antibody were done on 25,392 prostitutes working in 64 cities throughout the Philippines. The country-wide seropositivity rate among prostitutes based on this sample was 0.8/1,000. Of the HIV cases, 85% were working in just two cities whose prostitute populations comprised 50% of the total sample. The average incidence rate for the same two cities after 1 year was 2.3/1,000. HIV antibody-positive women were enrolled in a case-control study to determine demographic and epidemiologic risk factors. This study involving 34 HIV-positive prostitutes and 61 randomly selected negative control prostitutes did not reveal any risk factors related to sexual or other types of behavior. A history of genital warts, a history of abnormal vaginal discharge, and cytomegalovirus antibody were significantly more frequent in the HIV-positive cases than in the controls; however, by logistic regression analysis, only an abnormal vaginal discharge was independently associated with HIV infection. Absence of any evidence of transmission by blood transfusion or i.v. drug abuse suggests that HIV was introduced by the heterosexual route.

Isolation of dengue viruses from hospitalized patients in the Philippines, 1983-1986.

Between 1983-1986, 336 strains of dengue virus were isolated from 1,911 patients who had been hospitalized with clinically suspected DF/DHF in Manila and nearby areas. Multiple serotypes were present every year. Although DEN 3 was the most common serotype isolated (40%) over the entire study period, DEN 2 and DEN 1 were more frequently isolated in 1983 and 1984, respectively. DEN 4 was consistently the least common serotype recovered. During 1984, geographic differences in the pattern of serotypes isolated were found for two heavily populated areas located only 70 km apart. A higher proportion of DEN 2 isolates were recovered from patients with gastrointestinal bleeding compared to DEN 1 and DEN 3. A higher proportion of DEN 1 and DEN 3 isolates came from patients experiencing a 1 degree infection compared to DEN 2, and the mean homologous HI antibody titer of the sera that DEN 2 was isolated from was significantly higher than the homologous titers of sera from which DEN 1 and DEN 3 were isolated.

Dengue infections in the Philippines: clinical and virological findings in 517 hospitalized patients.

From May 1983 to January 1984, 517 patients with laboratory confirmed dengue were studied at a hospital in Manila. Secondary dengue infections were diagnosed in 78% of these cases. Peak admission (28%) occurred towards the end of the rainy season in November. Most patients (78%) were less than 15 years old but only 3 were infants. Although some type of hemorrhagic finding occurred in 460 cases (89%), only 110 were classified as dengue hemorrhagic fever and the remainder as dengue fever with hemorrhagic manifestations. The clinical course was usually mild. Gastrointestinal bleeding was present in 65 cases, but only 2 patients developed shock. No fatalities occurred. Dengue 2 was the predominant serotype with 53 isolates, followed by dengue 1 with 48 isolates, dengue 3 with 39 isolates, and dengue 4 with only 8 isolates. Dengue 2 was the only serotype with more isolates from sera with a homologous HI antibody titer greater than 1:20 (57%) than from sera with a homologous HI titer less than or equal to 1:20 (43%). In contrast, most of the dengue 1 isolates (63%) were from sera with a homologous HI antibody titer less than 1:10, and this serotype was strongly associated with primary infections. This study shows that dengue infections remain an important cause of pediatric hospitalization in the Philippines; however, the occurrence of life-threatening dengue hemorrhagic fever as has been described in several other large urban areas of Southeast Asia appears to be rare.