Jangu E. Banatvala

Maternal viral load, CD4 cell count and vertical transmission of HIV‐1

HIV load and CD4 cell numbers were measured among 95 HIV infected women during pregnancy in order to determine their value as prognostic markers for transmission of virus from mother to infant. Among the 94 live births, 13 children were infected with HIV, 69 were uninfected and 12 were of unknown infection status. HIV RNA levels, as measured by nucleic acid sequence based amplification, were significantly higher (P < 0.001) in women who transmitted virus than among those who did not transmit and maternal viral load was a stronger predictor of transmission than CD4 cell number. The predicted rate of transmission relative to maternal HIV RNA was 2% at 1,000 copies, 11% at 10,000 copies and 40% at 100,000 copies/ml. Little variation in viral load occurred during pregnancy and there was an association between viral load and prematurity, the mean gestation at delivery decreasing by 1.3 weeks for every 10‐fold increase in maternal HIV RNA (P = 0.007). This study demonstrates that a high level of maternal HIV RNA is a risk factor for transmission of virus to the infant and maternal viral load is of more value as a prognostic marker for transmission risk than CD4 cell number. High viral load is also associated with premature delivery. Maternal viral load is therefore a useful marker on which to base management decisions during pregnancy. J. Med. Virol. 54:113–117, 1998.

Comparison of human immunodeficiency virus type 1-specific inhibitory activities in saliva and other human mucosal fluids.

ABSTRACT Several human mucosal fluids are known to possess an innate ability to inhibit human immunodeficiency virus type 1 (HIV-1) infection and replication in vitro. This study compared the HIV-1 inhibitory activities of several mucosal fluids, whole, submandibular/sublingual (sm/sl), and parotid saliva, breast milk, colostrum, seminal plasma, and cervicovaginal secretions, from HIV-1-seronegative donors by using a 3-day microtiter infection assay. A wide range of HIV-1 inhibitory activity was exhibited in all mucosal fluids tested, with some donors exhibiting high levels of activity while others showed significantly lower levels. Colostrum, whole milk, and whole saliva possessed the highest levels of anti-HIV-1 activity, seminal fluid, cervicovaginal secretions, and sm/sl exhibited moderate levels, and parotid saliva consistently demonstrated the lowest levels of HIV-1 inhibition. Fast protein liquid chromatography gel filtration studies revealed the presence of at least three distinct peaks of inhibitory activity against HIV-1 in saliva and breast milk. Incubation of unfractionated and fractionated whole saliva with antibodies raised against human lactoferrin (hLf), secretory leukocyte protease inhibitor (SLPI), and, to a lesser extent, MG2 (high-molecular-weight mucinous glycoprotein) reduced the HIV-1 inhibitory activity significantly. The results suggest that hLf and SLPI are two key components responsible for HIV-1 inhibitory activity in different mucosal secretions. The variation in HIV inhibitory activity between the fluids and between individuals suggests that there may be major differences in susceptibility to HIV infection depending both on the individual and on the mucosal fluid involved.

Clinical trial with inactivated hepatitis A vaccine and recommendations for its use.

OBJECTIVE--To compare the reactogenicity and immunogenicity of an inactivated hepatitis A vaccine in two different immunisation schedules. DESIGN--Randomised trial. SETTING--One London teaching hospital. SUBJECTS--104 healthy adult volunteers (71 men, 33 women aged 19-60). INTERVENTIONS--Hepatitis A vaccine to group 1 (54 volunteers) at 0, 1, and 2 months and to group 2 (50) at 0, 1, and 6 months. MAIN OUTCOME MEASURES--Symptoms at and after each dose; liver function, hepatitis A virus specific serum immune response; and responses in saliva and parotid fluid in immunised volunteers and subjects with natural immunity. RESULTS--The vaccine was well tolerated; 97% (96/99) and 100% of those immunised developed serum antibody after one and two doses of vaccine respectively. Geometric mean titres increased progressively after each dose and were significantly higher in men but not women in group 2 after the third dose (ratio between geometric mean titres 0.265, 95% confidence interval 0.18 to 0.39; p less than 0.001). At one year this group-sex interaction was absent; geometric mean titres for both sexes were significantly higher in group 2 (ratio 0.330, 0.227 to 0.478; p less than 0.0001). Antibody responses were not significantly different between the groups at two years. Compared with naturally infected subjects immunised volunteers developed poor or undetectable virus specific IgG and IgA responses in saliva and parotid fluid. CONCLUSIONS--The vaccine was safe and highly immunogenic, and the differences in the immune responses in saliva and parotid fluid are unlikely to affect its efficacy.

Identification of hepatitis C virus seroconversion resulting from nosocomial transmission on a haemodialysis unit: Implications for infection control and laboratory screening

Hepatitis C virus (HCV) seroconversion was detected by routine screening in a haemodialysis patient, Patient 1. Serological investigations were undertaken over the following 3 months to determine if further transmission to other patients on the unit had occurred. No additional cases were identified. Twenty‐two haemodialysis patients known to have HCV infection were investigated using molecular epidemiological methods to determine if transmission between patients had occurred. HCV viraemia was demonstrated by polymerase chain reaction in 19 of 22 patients (86%). Genotyping showed that eight patients were infected with genotype 1, three with genotype 3 and eight, including Patient 1, with genotype 2. Phylogenetic analysis of viral sequences from the eight patients with genotype 2 revealed three, including Patient 1,with a novel subtype of HCV type 2, and revealed close similarity between viral sequences from patient 1 and those from one other patient, suggesting transmission. This was consistent with haemodialysis histories. Among other patients with genotype 2, there were two with subtype 2a and three others with three separate novel subtypes, as yet undesignated. With the exception of patient 1, all patients infected with novel subtypes were of Afro‐Caribbean origin. The HCV prevalence among patients on the haemodialysis unit was high (14%), which may reflect the ethnicity of our haemodialysis population. This case emphasises the risk of nosocomial transmission and the importance of infection control procedures on haemodialysis units, and highlights the usefulness of molecular epidemiological techniques for the investigation of outbreaks of HCV infection. J. Med. Virol. 59:135–140, 1999.

Near fatal chickenpox during prednisolone treatment

The incidence of chickenpox (varicella) is increasing; thus, the proportion of cases in England and Wales in those over 14 years of age has increased from 10% to 25% between 1970 and 1990.1 Although usually mild among children, varicella is often severe and occasionally life threatening in adults, particularly in those whose immune systems have been suppressed by disease or treatment with corticosteroids.2,3 Corticosteroids are widely prescribed: over 5.5 million prescriptions for systemic corticosteroids were issued by general practitioners in the United Kingdom for the year ending September 1993 (Intercontinental Medical Statistics, personal communication). We describe a case of severe chickenpox in a patient being treated with high dose corticosteroids and put forward recommendations to reduce the risk of further cases.nnPatients taking corticosteroids who are susceptible to chickenpox must receive immediate prophylaxis on contact with varicella; the steroid card should be amendednn### Case reportnnWe admitted a 27 year old woman with a 36 hour history of severe lower back pain. She had been taking steroids for six weeks; she started taking prednisolone 60 mg daily for idiopathic thrombocytopenia, but for the two weeks before admission she had been taking 30 mg daily. Twenty four hours after admission she developed a fever of 37.8°C and a maculopapular eruption with vesicles over the neck and shoulders. Vesicular fluid contained herpes virus particles, and we confirmed varicella zoster virus by immunofluorescence. The patient had not had chickenpox before, but she had been in contact with fellow students from her college, where there had been a number of recent cases.nnWe started treatment with …

Significance of placental damage in vertical transmission of human immunodeficiency virus

The significance of physical breaches of the trophoblastic layer of the placenta in transmission of HIV from mother to infant was evaluated in 17 HIV‐infected pregnant women. Samples of peripheral blood were obtained from the women during pregnancy and at delivery, at which time a small piece of placental tissue was obtained from a random site and immediately placed into fixative. Blood samples were obtained from infants at or shortly after birth and thereafter at approximately 3‐month intervals, until the age of 18 months, in order to determine their HIV infection status. HIV RNA and p24 antigen were quantified in maternal plasma and CD4 cells enumerated. Paediatric diagnosis was conducted using polymerase chain reaction, virus isolation, detection of p24 antigen, and measurement of class‐specific antibodies. Placental damage was quantified and evaluated using transmission electron microscopy. Maternal viral load was low, with a mean RNA copy number of 8,237 per millilitre of plasma (range 230–37,233 copies/ml). Only two women were p24‐antigenaemic, and CD4 numbers ranged from 0.09 to 2.8 × 109/l. There was evidence of breaks in the trophoblastic surface to the depth of the basement membrane in all 17 placentas, and perivillous fibrinoid deposits were also observed to a varying degree in all samples. However, none of the 13 infants available for follow‐up had evidence of infection with HIV. Superficial damage to the trophoblastic surface of the placenta, with exposure of the basement membrane and potential exposure of CD4‐expressing cells, does not appear to be a significant factor in the transmission of HIV from mother to infant during pregnancy.

Effect of hepatitis A vaccination schedules on immune response

An inactivated hepatitis A vaccine was given to 104 seronegative volunteers aged between 19 and 60 years according to two schedules: 0, 1 and 2 months or 0, 1 and 6 months. The vaccine was well tolerated and 97 and 100% of vaccinees developed a serum antibody response following a single and two doses of vaccine respectively. Geometric mean titres increased progressively after each dose; responses following the 0, 1, 6 month schedule were significantly higher at one year but, among those tested at two years, these differences were less marked. Vaccinees, when compared with naturally infected persons, developed poor or undetectable hepatitis-A-virus-specific immunoglobulin G and A antibody responses in saliva and parotid fluid. Such differences are, however, unlikely to affect the protective efficacy of the vaccine.

Antenatal HIV testing: current problems, future solutions. survey of uptake in one London hospital

Pregnant women attending Guys and St Thomass Hospitals Trust have one of the highest prevalence rates for HIV-1 in inner London (0.53% in 1996).1 In 1992 we showed that this was associated with African ethnic origin.2 However, despite the Department of Healths recommendations that named HIV testing be made available to all pregnant women in areas of relatively high prevalence, uptake in our trust is disappointingly low—about 30%—as elsewhere in inner London. In 1995, throughout London, only 26 of 205 (13%) HIV positive pregnant women had been identified antenatally.3 Most were therefore almost certainly unable to benefit from recent advances in treatment and in the prevention of mother to child transmission of HIV.nnThis paper describes uptake of HIV testing among pregnant women between 1991 and 1996 and includes a detailed survey of 789 women, of whom 428 attended antenatal clinics at Guys Hospital, 310 attended six …