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Biomedical subjects

P Palasanthiran

Publications and source records attributed to P Palasanthiran.

15 recordsLinked to original sources
PubMed2005

Improved neurodevelopmental outcomes following long-term high-dose oral acyclovir therapy in infants with central nervous system and disseminated herpes simplex disease.

OBJECTIVE: Infants with neonatal herpes, classified as central nervous system or disseminated disease, have a high incidence of moderate and severe neurologic deficits despite standard acute therapy. STUDY DESIGN: Following completion of parenteral therapy, infants with central nervous system and/or disseminated disease received 2 years of continuous oral acyclovir therapy. Target minimum peak serum acyclovir concentrations were >2 microg/ml for the first three patients, and >3 microg/ml for the subsequent 13 patients. Safety assessments were made every 3 months. We evaluated neurodevelopmental outcomes with Bayley Scales of Infant Development. RESULTS: A total of 16 consecutive herpes simplex virus-infected infants born during 1990 to 2003 received the treatment plan; 13/16 infants had central nervous system disease; 3 had disseminated disease without central nervous system involvement. A total of 69% (11/16) had Bayley scores in the normal range for mental development and 79% (11/14) had motor scores in the normal range. At the final assessment, five children had developmental delays. One child had severe mental delay with normal motor development. Four children had mild mental delays, with severe motor delays in three. All children were independently mobile, without seizure disorder, had normal vision, and had speech development. During the 2-year course of treatment, five children had brief recurrences of dermal lesions, and none had evidence of neurologic deterioration. There were no serious or sustained adverse drug reactions. CONCLUSION: This pilot study reports improved outcomes in a small cohort of infants with a prolonged course of oral acyclovir. A minority of these children exhibited mild or significant developmental delays. Further investigation of this approach to treatment is warranted.

Acyclovir↗
PubMed1999

A population-based study of children with cerebral tuberculosis in New South Wales.

OBJECTIVE: To determine the incidence of childhood cerebral tuberculosis (tuberculous meningitis [TBM] and tuberculoma) in a defined population. DESIGN: Retrospective, population-based study. SETTING AND PARTICIPANTS: All resident children aged up to 14 years in New South Wales diagnosed with cerebral tuberculosis, from 1982 to 1996. MAIN OUTCOME MEASURE: Population-based incidence of childhood TBM. RESULTS: 10 children with TBM and one with tuberculoma were identified in the 15 years. The incidence of TBM was 0.053 (95% CI, 0.025-0.097) per 100,000. Eight of the 10 TBM patients were born in Australia and five were of white European origin. Only one had been vaccinated with BCG vaccine. Three of the children died. CONCLUSIONS: The incidence of childhood TBM in New South Wales is low, and comparable with that in other First World countries.

Adolescent↗
PubMed1997

Molecular analyses of human immunodeficiency virus type 1 V3 region quasispecies derived from plasma and peripheral blood mononuclear cells of the first long-term-nonprogressing mother and child pair.

Molecular analyses were done for the V3 region quasispecies of human immunodeficiency virus type 1 (HIV-1) strains from plasma and peripheral blood mononuclear cells of the first HIV-1-infected long-term-nonprogressing mother-child pair whose members have survived for >13 years with stable CD4 T cell counts. There was a predominance of lower V3 loop charge and the absence of genotypic changes that are critical in phenotypic determination and tropism during HIV-1 infection. The intrahost genetic diversity between HIV-1 strains from the mother-child pair compared with HIV-1 strains from slow and rapid progressors suggested that a high genetic heterogeneity in HIV-1 strains from this HIV-1-infected long-term-nonprogressing mother and child pair was directly proportional to the length of their immunocompetent period.

Amino Acid Sequence↗
PubMed1997

Paediatric HIV update.

Less than half of the paediatric HIV infections recorded in Australia have resulted from perinatal transmission, but in recent years this has been the predominant mode of infection. There are 136 infants who are known to have been exposed perinatally to HIV in Australia: 49 of these are infected. Caesarean section is thought now not to reduce the risk of perinatal transmission (PNT); rather, the risk increases with duration of membrane rupture and rises rapidly after 4 h of membrane rupture. However, no data exist to show that interventions to expediate delivery after membrane rupture reduce the risk of PNT. Data such as these suggest that the majority of perinatal infections (probably about 60%) occur close to the time of delivery. While the overall risk of PNT for non-breast fed infants is approximately 20-25%, the risk of infection for the infant is considerably increased when there is evidence of increased maternal viral burden. Advanced maternal disease predicts that if the infant is infected there is more likely to be early progression of HIV than is the case for the less frequently infected infants of mothers who are asymptomatic. Bottle feeding may prevent infection of 10% of children exposed perinatally. Use of zidovudine by the mother in the third trimester and i.v. zidovudine during labour, followed by oral zidovudine for the infant for 6 weeks can reduce the PNT rate by two thirds, to about 8%. Approximately 3% of uninfected infants with perinatal HIV exposure may be found to be transiently virus positive but eventually become antibody negative and thus appear to have eliminated the virus. The risk of Pneumocystis carinii pneumonitis (PCP) cannot be predicted on the basis of CD4 count and it is recommended that all children of infected mothers commence PCP prophylaxis around the age of 6 weeks-2 months and continue that therapy until the age of 12 months or until it becomes clear that the infant is uninfected. The cumulative risk of AIDS increases rapidly during the first year of life to about 20%, then more slowly at a rate of about 2 or 3% a year. The shape of this curve reveals the bimodal progression of HIV disease in children. About 15-20% of children rapidly develop a severe immune deficiency, opportunistic infections and, in most cases, encephalopathy. There is a very high morbidity rate in this group of children, most of whom die before the age of 3 or 4 years. In contrast, 80-85% of children only become immunodeficient after a relatively long period, which is similar to or perhaps even longer than that in adults. Recent studies indicate that zidovudine antiviral monotherapy is no longer appropriate. While no clear alternative to monotherapy has emerged most would, wherever possible, commence antiretroviral therapy with a combination of two or three drugs including zidovudine plus didanosine or lamivudine. If a third drug is used it would probably be a protease inhibitor.

AIDS-Related Opportunistic Infections↗
PubMed1996

Gene defects clustered at the C-terminus of the vpr gene of HIV-1 in long-term nonprogressing mother and child pair: in vivo evolution of vpr quasispecies in blood and plasma.

Earlier studies on HIV-1 strains from HIV-1-infected long-term nonprogressors (LTNP) have reported that nef deletions and/or attenuations may be crucial in the survival of these patients. Other reports have suggested that the nef gene may not be the only gene involved, but attenuations in other accessory genes (vif, vpr, vpu), which play an important role in the viral life cycle, may be similarly important in chronic HIV-1 infection in LTNPs. Here we show the molecular and phylogenetic analyses of the vpr gene in HIV-1 strains derived from both blood and plasma of an HIV-1 infected long-surviving mother-child pair which has survived for > 13 years with HIV infection: both have maintained stable CD4+ T-cell counts. Analyses of blood-and plasma-derived HIV-1 vpr clones indicated the presence of defects (insertions and deletions) and length polymorphisms. Interestingly, all the vpr defects in PBMCs and plasma were clustered at the C-terminus of the Vpr protein, between amino acid residues 83 and 89, which has been implicated in the G2 cell cycle arrest as a step to early HIV-1 infection. In contrast, the vpr sequence analysis of HIV-1 strains derived from 30 different patients, who either died of AIDS-related illnesses or have AIDS, showed neither C-terminal defects nor length polymorphism in the vpr gene. Also, secondary structure predictions suggest that the naturally occurring mutations at the C-terminal region (aa 83-89) have the potential to affect the secondary structure of the Vpr protein. Also, in some cases, the out-of-frame mutations and the length polymorphisms affect the tat gene reading frame. Together, these mutations may have potential significance in conferring chronic HIV-1 infection in this long-surviving nonprogressing mother-child pair.

Adolescent↗
PubMed1996

An HIV-1 infected long-term non-progressor (LTNP): molecular analysis of HIV-1 strains in the vpr and nef genes.

We describe a long-term non-progressive injecting drug user (IDU) who was infected with human immunodeficiency virus type-1 (HIV-1) in 1984, and has survived with stable CD4+ T-cell counts (> 800/microliters blood) without any acquired immune deficiency syndrome (AIDS) related illness. With a goal to investigate the molecular nature of HIV-1 strains infecting this patient, we amplified the nef and vpr genes directly from the fresh uncultured peripheral blood mononuclear cells (PBMCs), and carried out co-culture studies. Sequence analysis of the nef gene (from 1994 samples) showed no deletions (as has been previously reported) expected for a 7 base pair duplication at the C-terminus which prematurely terminated the nef reading frame, whereas even after repeated attempts the nef gene could not be amplified from the 1992 PBMC samples. In contrast, the vpr gene (from 1992 and 1994 samples) revealed two distinct quasispecies with no apparent defects. We observed five amino acid substitutions, between residues 83-90, at the C-terminus which has been recently implicated in G2 cell cycle arrest as an early step to HIV-1 infection. In the light of recent evidence on the role of nef gene defects/attenuations in long-term survival of HIV-1 infected patients, it may be that the nef gene defect created by gene duplication, which eliminated the cysteine-206 crucial in disulfide bond formation, may play a role in chronic HIV-1 infection in this patient. These data further suggest that deletions in the nef gene may not be the only reason for long-term non-progression of HIV-1 infection in some individuals, but the gene defects like duplication and subtle mutations in the functional motifs of both nef and vpr genes may confer similar protection in HIV-1 infected patients surviving for longer periods of time with stable CD4 counts.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Decay of transplacental human immunodeficiency virus type 1 antibodies in neonates and infants.

Transplacental human immunodeficiency virus (HIV) antibodies from 11 uninfected and 3 infected infants of HIV-seropositive mothers were measured using end point titration of twofold dilutions of sera by a particle-agglutination method. Four or more sequential serum samples from each infant were collected between birth and age > or = 14 months and analyzed. Linear regression of log2 antibody titers of uninfected infants plotted against age (days) showed an exponential decay in maternal HIV antibodies. The mean half-life of passive HIV antibodies was 23.1 +/- SD 4.2 days (range, 18.2-29.3; 95% confidence interval, 20.2-26.0). The median age of clearance of maternal HIV antibodies was 13.3 months (range, 10.4-15.6). A model assuming first-order exponential decay and production of HIV antibodies was fitted to the time course of antibody titers of the infected infants. Minimal titers in each infected infant occurred at 5.5, 4.9, and 4.0 months, and doubling times of HIV antibodies from that point ranged from 16.8 to 31.4 days.

Agglutination Tests↗
PubMed1994

Early detection of human immunodeficiency virus type 1 infection in Australian infants at risk of perinatal infection and factors affecting transmission.

The earliest, most reliable methods for detecting human immunodeficiency virus type 1 (HIV-1) infection in infants at risk of perinatal HIV-1 and risks for transmission were investigated. Fifteen infants were followed prospectively from birth to age 21 to 48 months. Epidemiologic data on mothers during pregnancy were documented, and maternal proviral load (by quantitative polymerase chain reaction) and viral phenotype by HIV isolation were performed. Infants were assessed clinically and HIV isolation, HIV p24 antigen, polymerase chain reaction and total serum immunoglobulin determinations were performed. Four infants were infected. HIV isolation, HIV p24 antigen and polymerase chain reaction were positive within 3 months in all infected infants (100% sensitivity). False positive rates for a single test were 18, 9 and 9%, respectively. Median age of clearance of maternal antibodies was 13.4 +/- 2.1 months. Serum immunoglobulin G was significantly elevated after 6 months in all 4 infected infants. Advanced maternal age (> or = 30 years; Fisher's exact test, P > 0.014) was associated with transmission. A trend in higher maternal viral burden was observed among transmitters. Non-syncytium-inducing phenotype was present initially in all transmitting mothers.

Analysis of Variance↗
PubMed1993

Breast-feeding during primary maternal human immunodeficiency virus infection and risk of transmission from mother to infant.

Examination of breast-fed infants of the complete cohort of Australian women whose primary human immunodeficiency virus (HIV) infection occurred postpartum allows for an estimate of risk of transmission of HIV. Ten women with no other risk factors were infected via blood transfusion postpartum. They breast-fed for up to 9 months; 2 of their infants were infected. Another woman, who shared needles for intravenous drug use, seroconverted 6-10 months post-partum. She breast-fed for 14 months. Retrovirus was visualized in the cellular and cell-free fraction of her milk by electron microscopy. Infection in her infant was confirmed at 12 months. Thus, 3 of the 11 babies at risk became infected, providing an estimate of risk of 27% for breast-feeding during primary maternal infection (95% confidence interval, 6-61%). These data establish the association of primary maternal HIV infection and breast-feeding with a high risk of transmission to infants.

Animals↗
PubMed1993

Pediatric HIV: Australian perspective.

Pediatric infection with human immunodeficiency virus (HIV) in Australia, as elsewhere, now reflects HIV seroprevalence in women of childbearing age although numbers remain small. A perinatal transmission rate of approximately 30% has been observed. The rate appears to be higher for breast-fed babies; exclusively bottle-fed babies of HIV-infected mothers appear to have a risk of < 20% of acquiring HIV perinatally. Although the seroprevalence rate in women of childbearing age in Australia remains low, routine antenatal screening will not be cost-effective. Although passively acquired maternal antibody may confound serodiagnosis for up to 18 months, in practice, HIV infection, when present, can be detected clinically or with use of other laboratory parameters (p24, polymerase chain reaction, viral culture, hyperglobulinemia) during the first 6 months of life. Zidovudine appears to be relatively nontoxic in children and effective in producing weight gain and preventing opportunistic infection. Although experience with didanosine is limited, this drug appears to have a very acceptable toxicity profile and the advantage of twice-daily dosing. However, the bioavailability and penetration into the cerebrospinal fluid are poor. Neurological disease can improve when absorption is adequate. Residential family camps may help to reduce isolation for families and provide them with an opportunity for improving their understanding of HIV through interaction with peers and professionals.

Adult↗
PubMed1990

Zidovudine (AZT) therapy in children with HIV infection: the Australian experience.

Fifteen children (11 males and four females), on oral Zidovudine (AZT) for symptomatic HIV infection were studied retrospectively. Twelve acquired HIV via blood products, two from vertical transmission (maternal intravenous needle sharing) and one through breast feeding. Their mean age at the start of therapy was 8.6 years (s.d. 4.4 years, range 1.8-15.3 years). The main indications for therapy were failure to thrive (FTT) in 10, recurrent respiratory tract infections (RRTI) in eight, and developmental delay (DD) in one, with overlapping indications being Pneumocystis carinii pneumonia (PCP) in one and pulmonary lymphoid hyperplasia (PLH) in two. The mean commencement dose was 24 mg/kg per day orally in 3-6 divided doses (range 16-35 mg/kg per day). The duration of therapy was 2 weeks-2 1/2 years. Significant improvement in growth was observed by 2 months; at 6 months, growth was sustained in these otherwise ill children, with only two falling below pretreatment weight. Decrease in the frequency of RRTI based on subjective reports of the attending clinicians was observed in seven of the eight evaluable children still on therapy. Improvement in PCP and PLH occurred in two children and modest improvement was subjectively reported in PLH in one while still early in the course of therapy. Overall, AZT was well tolerated. Dose modifications were for neutropenia in three (of which only two were drug related), rapidly falling neutrophil count in one, anaemia in two (with concurrent history of chronic gastrointestinal tract blood loss in one), severe GIT irritation in one and transient sedation in one. Seven opportunistic infections were reported (three in the same patient) of which two occurred following cessation of therapy, one after only 2 weeks of therapy, and one had not been on primary prophylactic therapy. Three deaths occurred, one associated with opportunistic infections and two while off therapy (one respiratory failure, one PCP).

Adolescent↗