Subject(s)
HIV Infections/prevention & control , Mothers , Parental Consent , Research Subjects , Adolescent , Female , Humans , Pilot Projects , South Africa , Vulnerable PopulationsSubject(s)
Asymptomatic Infections/epidemiology , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Pregnancy Complications, Infectious/epidemiology , Sentinel Surveillance , Betacoronavirus , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Female , Humans , Mass Screening , Pandemics , Pneumonia, Viral/diagnosis , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Prenatal Care , Research , SARS-CoV-2 , South Africa/epidemiologySubject(s)
Cannula , Coronavirus Infections , Pandemics , Pneumonia, Viral , Respiratory Insufficiency , Betacoronavirus , COVID-19 , Humans , Oxygen , Oxygen Inhalation Therapy , Phenotype , SARS-CoV-2ABSTRACT
Reproduction is a crucial stage in the naturalisation of introduced plant species. Here, using breeding system experiments and observations of floral visitors, we investigate whether a lack of pollinators or an inability to autonomously self-fertilise limits naturalisation in five Australian Banksia species and the co-familial Hakea salicifolia in South Africa. Banksia species were heavily utilised by native insects and nectar-feeding birds. Although Banksia produced fruit when pollinators were excluded, pollinators significantly increased seed set in four of the five species. H. salicifolia flowers were visited by 11 insect species; honeybees (Apis mellifera) were the main visitors. Flowers in naturalised H. salicifolia populations received almost four times the number of visits as flowers in non-naturalised populations; the latter showed both pollen limitation (PLI 0.40) and partial self-incompatibility. This should not prevent invasion, since H. salicifolia produces fruits via autonomous selfing in the absence of pollinators. The results suggest a limited role of breeding systems in mediating naturalisation of introduced Proteaceae species. Other factors, such as features of the recipient environments, appear to be more important. Spatial variation in rates of reproduction might, however, explain variation in the extent and rate of naturalisation of different populations.
Subject(s)
Pollination/physiology , Proteaceae/physiology , Self-Fertilization/physiology , Animals , Australia , Bees , Flowers/physiology , Insecta , Introduced Species , Pollen , Seeds/growth & development , South AfricaABSTRACT
Chronic air pollution exposure during pregnancy can cause oxidative stress leading to adverse birth outcomes. The aim of this study was to assess and compare oxidative stress response in peripheral lymphocytes isolated from pregnant women from a highly industrialized locale (south Durban (SD); n = 50) and a control with lower air pollutant levels (north Durban (ND); n = 50). Oxidative stress response was measured by quantifying malondialdehyde (MDA) levels and a SuperArray gene panel. Mitochondrial function (adenosine triphosphate (ATP) levels and mitochondrial depolarization), DNA integrity (comet assay and mitochondrial DNA (mtDNA) viability) and DNA repair (OGG1) were assessed. Antioxidant response was assessed by quantification of glutathione (GSH) and SOD2, nuclear factor erythroid 2-related factor 2 (Nrf2) and uncoupling protein 2 (UCP2) protein and messenger RNA (mRNA) expression. Levels of MDA (p = 0.9), mitochondrial depolarization (p = 0.88), ATP (1.89-fold), SOD2 (1.23-fold) and UCP2 (1.58-fold) gene expression were elevated in the SD group with significantly higher UCP2 protein levels (p = 0.05) and longer comet tail length (p = 0.0004). The expression of Nrf2 protein (p = 0.03) and mRNA levels (-1.37-fold), GSH concentration (p < 0.0001), mtDNA amplification (-2.04-fold) and OGG1 mRNA (-2.78-fold) activity were decreased in the SD group. Of the 84 oxidative stress-related genes evaluated, 26 were differentially regulated. Pregnant women exposed to higher air pollutant levels showed increased markers for oxidative stress and compromised DNA integrity and repair.
Subject(s)
Air Pollution , Maternal Exposure , Oxidative Stress , Antioxidants/metabolism , DNA Damage , Female , Humans , Pregnancy , South AfricaABSTRACT
Each year thousands of adolescent girls and young women in South Africa (SA) become pregnant and many die from complications related to pregnancy and childbirth. Although women of all ages are susceptible, girls<15 years of age are five times as likely, and those aged 15-19 years twice as likely, to die from complications related to childbirth than women in their 20s. In SA, non-pregnancy-related infections (e.g. HIV), obstetric haemorrhage and hypertension contributed to almost 70% of avoidable maternal deaths. In addition to the implementation of standardized preventive interventions to reduce obstetric haemorrhage and hypertension, better reproductive health services for adolescents, access to HIV care and treatment for women infected with HIV, and improved access to and uptake of long-acting reversible contraception are important ingredients for reducing maternal mortality among adolescents.
Subject(s)
Maternal Mortality , Pregnancy Complications/prevention & control , Pregnancy in Adolescence , Adolescent , Female , HIV Infections/drug therapy , HIV Infections/prevention & control , Humans , Mass Screening , Pregnancy , Pregnancy, Unwanted , Prenatal Care , South Africa/epidemiologyABSTRACT
BACKGROUND: Sub-Saharan Africa is endemic for hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections. HBV/HIV co-infection in women of reproductive age is of clinical and public health importance because these women constitute a significant reservoir for horizontal and perinatal HBV transmission. Childhood HBV vaccination from 6 weeks of age protects most children against chronic HBV infection. However, infants born to HBV/HIV co-infected women are more likely to be infected perinatally, with an increased risk of chronic hepatitis, than infants born to HBV mono-infected women. OBJECTIVES: The aim of our study was to establish the prevalence of HBV infection and HBV/HIV co-infection in pregnant women in KwaZulu-Natal, South Africa, to inform antenatal HBV screening and childhood immunisation policies in South Africa. METHODS: Stored plasma specimens obtained from 570 pregnant women were tested for hepatitis B surface antigen (HBsAg) and HBV infectivity, as characterised by the presence of hepatitis B e antigen (HBeAg) and/or HBV DNA load. RESULTS: The antenatal HIV prevalence and HBsAg prevalence in this study were 41.6% and 5.3% (95% confidence interval (CI) 3.4 - 7.1), respectively. Overall, 3.1% (95% CI 1.7 - 4.6) of pregnant women were HBV/HIV co-infected, with HBeAg positivity and the HBV DNA load being significantly higher in co-infected women. CONCLUSION: We report a 5.3% HBV prevalence and a 3.1% HBV/HIV co-infection prevalence in pregnant women from this HIV-endemic region. Routine antenatal HBV screening will allow early identification of neonates who require HBV active-passive immunoprophylaxis at birth. This strategy, together with antenatal antiretrovirals, will reduce the risk of perinatal HBV transmission, especially in high-risk HBV/ HIV co-infected pregnant women.
Subject(s)
DNA, Viral/blood , HIV Infections/epidemiology , Hepatitis B, Chronic/epidemiology , Pregnancy Complications, Infectious/epidemiology , Adolescent , Adult , Coinfection/blood , Coinfection/epidemiology , Female , HIV Infections/blood , Hepatitis B Surface Antigens/blood , Hepatitis B virus/genetics , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/transmission , Humans , Infectious Disease Transmission, Vertical , Middle Aged , Pregnancy , Pregnancy Complications, Infectious/blood , Prenatal Diagnosis , Prevalence , Viral Load , Young AdultABSTRACT
INTRODUCTION: Chronic myeloid leukaemia (CML) is a chronic myeloproliferative disorder characterised by a chromosomal translocation between the long arms of chromosomes 9 and 22 [corrected] resulting in the formation of the BCR-ABL fusion gene. The management of CML has undergone major changes over the past decade. Novel treatment approaches have had a dramatic impact on patient outcomes and survival. Nevertheless, these outcomes can only be achieved in the context of expert management, careful monitoring of disease response, appropriate management of adverse events and timeous adjustments to therapy when responses are not achieved within stated time-frames. AIM: With the advent of novel treatments providing molecular responses, both the monitoring and management of CML have become more complicated. The aim of these recommendations was to provide a pragmatic yet comprehensive roadmap to negotiate these complexities. METHODS: Recommendations were developed based on local expert opinion from both the academic and private medical care arenas after careful review of the relevant literature and taking into account the most widely used international guidelines. About five meetings were held at which these recommendations were discussed and debated in detail. RESULTS: A comprehensive set of recommendations was compiled with an emphasis on diagnosis, investigation, treatment and monitoring of disease. Careful attention was given to circumstances unique to South Africa, funding constraints, availability and access to laboratory resources, as well as the effects of concurrent HIV infection. CONCLUSION: Most patients with CML can live a reasonably normal life if their disease is appropriately managed. These recommendations should be of value to all specialists involved in the treatment of haematological disorders.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Adult , Benzamides , Comorbidity , Dasatinib , Disease Management , HIV Infections/epidemiology , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/epidemiology , Piperazines/administration & dosage , Piperazines/therapeutic use , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/therapeutic use , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyrimidines/administration & dosage , Pyrimidines/therapeutic use , South Africa , Thiazoles/administration & dosage , Thiazoles/therapeutic use , Treatment OutcomeABSTRACT
Conversion of lowland woodland to agricultural land and resulting fragmentation in Britain has been ongoing since Neolithic times. To counteract this decline, plantations of native species, often based on non-British planting stock, have been established. This may ultimately be detrimental to the integrity of the native gene pool. We explore the genetic and ecological factors influencing the success of components of the local pollen pool, including the effect of a non-native planting on an ancient woodland population of wild cherry. Wild cherry exhibits gametophytic self-incompatibility (GSI) and vegetative reproduction, both of which may be determinants of paternal success. The majority (61%) of the successful pollen originated from within the study site with a maximum pollen transfer distance of 694 m. There was a distinct departure from random mating, with over half the successful pollen originating from trees which occur within 100 m of the mother tree. Self-incompatibility, clonality, tree size and proximity to the mother tree were all found to influence paternal success. Kinship of pollen gametes within a maternal progeny was highest when a mother tree was surrounded by a large number of ramets of a single, compatible clone consisting of large, adult trees. Although the contribution from the non-native plantation is currently low, it is likely that this will increasingly contribute to the progeny of the adjacent ancient population as it matures. The results clearly show that in self-incompatible species, such as P. avium, close neighbours may be pollinated by very different components of the local pollen pool.
Subject(s)
Ecology , Prunus/genetics , Gene Frequency , Pollen , Pollination , ReproductionABSTRACT
Insights into the within-population spatial-genetic structure (SGS) of forest tree species, where little is known regarding seed and pollen dispersal patterns, enhance understanding of their ecology and provide information of value in conservation and breeding. This study utilised 13 polymorphic simple sequence repeat loci to investigate the impact of asexual recruitment, management regime and tree size on the development of SGS in wild cherry (Prunus avium L). Only 246 genotypes were identified in the 551 trees sampled, reflecting significant levels of clonal reproduction in both managed and unmanaged populations. Naturally regenerated wild cherry was spatially aggregated under both management regimes. However, in the managed population, sexually derived trees accounted for a greater proportion of the smaller size classes, whereas vegetatively produced trees dominated the smaller size classes in the unmanaged population. High overall SGS values (Sp 0.030-Sp 0.045) were observed when considering only sexually derived genets and kinship coefficients were significant up to the 120 m distance class for both populations. The inclusion of clonal ramets in the analysis significantly increased the overall SGS (Sp 0.089-Sp 0.119) as well as kinship coefficients in the 40-80 m distance classes, illustrating the dramatic impact of vegetative propagation on SGS in this species. Increased spatial aggregation and regeneration appeared to be concomitant with increased SGS in the 40 m distance class in the unmanaged population. Neighbourhood size estimates were relatively small for both populations and kinship coefficients were found to decline with distance under both management regimes, suggesting that common mechanisms may restrict gene dispersal in wild cherry.
Subject(s)
Genetics, Population , Models, Genetic , Prunus/genetics , DNA, Plant/genetics , Demography , Genetic Markers , Genetic Variation , Genotype , Minisatellite Repeats/genetics , Plant Physiological Phenomena , Population Density , Reproduction, AsexualABSTRACT
UNLABELLED: The aim of this study was to compare the cytotoxicity of a recently available dentine bonding agent on four different cell-lines (three human dental pulp fibroblast cell-lines and one mouse 3T3 fibroblast cell-line). METHODOLOGY: Three human dental pulp cell-lines from 3 different donors and one established 3T3 mouse cell-line were grown and sub-cultured. Cell viability following exposure to Scothbond was then compared to a similar number of controls using the MTT assay. RESULTS: Scotchbond 1 was cytotoxic to all four cell-lines. 3T3 cells showed a survival rate of about 60% as compared to two of the human dental pulp cells which showed a significantly lower survival rate (p<0.05, Kruskal-Wallis Multiple-Comparison Test). CONCLUSION: These findings indicated that is cytotoxic to both human pulp and 3T3 cell-lines. In general, the human pulp cell-lines showed higher sensitivity than the 3T3 cell-lines. CLINICAL SIGNIFICANCE: Scotchbond 1 cannot be recommended for direct pulp capping techniques and care should be taken when using this dentine bonding agent in cavities where the remaining dentine layer is minimal.
Subject(s)
Dental Pulp/drug effects , Dentin-Bonding Agents/toxicity , Resin Cements/toxicity , 3T3 Cells , Adult , Animals , Cell Line , Cell Survival/drug effects , Dental Pulp/cytology , Dental Pulp Capping , Fibroblasts/drug effects , Humans , MiceABSTRACT
The HIV global epidemic is having a devastating effect on women of reproductive age; women aged 15-24 years are 2.5 times more likely to be infected than young men in the same age group. Further, mother-to-child transmission (MTCT) accounts for almost two-thirds of the new infections that occur in children world-wide, annually. MTCT of HIV-1 varies widely and is dependent on obstetric practices, mode of delivery, breastfeeding, and the level of the viral load in the mother. Antiretroviral therapy (ARV) in pregnancy is prescribed for two main reasons: (i) women who need ARV medication for their own health; (ii) women who do not need treatment, or do not have access to treatment are offered prophylaxis to prevent MTCT, using one of a number of ARV regimens known to be effective. HIV infection is also associated with significant maternal morbidity and mortality. Clinicians caring for HIV-infected women need to update their knowledge continuously to provide optimal care.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV-1 , Pregnancy Complications, Infectious/drug therapy , Adolescent , Adult , Antiretroviral Therapy, Highly Active , Developed Countries , Developing Countries , Female , HIV Infections/transmission , HIV Infections/virology , Humans , Infant Mortality , Infant, Newborn , Infectious Disease Transmission, Vertical , Maternal Mortality , Pregnancy , Pregnancy Complications, Infectious/virology , Viral LoadABSTRACT
The objective of this study was to investigate the cytotoxicity and effect of concentration of a recent dentine bonding agent on a mouse fibroblast cell-line (3T3) and four different human pulp fibroblast cell-lines. A mouse fibroblast 3T3 cell-line and 4 different human pulp fibroblast cell lines were used. The cells were grown and subcultured using standard conditions. For the testing of the cytotoxicity of the bonding agent (Prime & Bond NT) it was extracted with DMEM medium and the different cell-lines were exposed to the extraction. The MTT assay was used to establish the number of viable cells. For all 5 pairs (control vs test sample) of cell-lines for 4 microl bonding agent, the mouse and only two of the four human cell-lines showed a statistical significant difference (p < 0.05; Mann-Whitney) due to the cytotoxicity of the bonding agent. However, all 5 pairs showed significant differences (p < 0.05) at the 8 microl concentration level. To investigate the relative effect of concentration (4 microl compared to 8 microl) of a chemical agent (we used a bonding agent, Prime & Bond NT) on the cytotoxicity of these 5 cell-lines, the Kruskal-Wallis Multiple-Comparison test was used on the standardised medians. Statistically significant differences (p < 0.05) were found for various cell-lines between both concentration levels. In general, the tested bonding agent, at a higher concentration level, has an increased cytotoxic effect on all 5 cell-lines. About 69% (median) of 3T3 cells stayed viable with 4 microl (0.94cm2/ml) bonding agent and 61% when 8 microl was used. For the pulp cells the percentages were between 91% and 72% for 4 microl and between 77% and 24% for 8 microl. These findings indicated that the bonding agent Prime and Bond NT was cytotoxic and that different human pulp fibroblast cell-lines should be used in the cytotoxic testing of dental materials and secondly, if only one concentration is to be used it should be in the higher range of that suggested by the ANSI/ADA document (2000, Revision) for recommended standard practices for biological evaluation of dental materials.
Subject(s)
Dental Pulp/drug effects , Dentin-Bonding Agents/toxicity , Fibroblasts/drug effects , 3T3 Cells , Animals , Cell Count , Cell Line , Cell Survival/drug effects , Coloring Agents , Dose-Response Relationship, Drug , Humans , Mice , Polymethacrylic Acids/toxicity , Tetrazolium Salts , ThiazolesABSTRACT
BACKGROUND: Increases in perinatal TB have paralleled the exacerbation of the TB epidemic in KwaZulu Natal. The exact risks for vertical transfer of Mycobacterium tuberculosis (VTRTB) to the baby are unknown, as is the impact of HIV-1 co-infection, which frequently accompanies maternal TB disease in the region. DESIGN: Prospective case series study of 82 HIV-1-infected and 25 non-infected pregnant mothers, King Edward VIII Hospital, KwaZulu Natal, South Africa. RESULTS: Perinatal mortality in HIV-1/TB diseased mothers was 85/1000 and associated with maternal anaemia (P = 0.02); 46% of newborns were premature, 66% low birth weight and 49% intrauterine growth restricted. These were significantly higher than overall hospital rates (P < 0.01, OR 4.8, 95%CI 3.2-7.0). Sites of detection of maternal TB, distribution of bacteriologically-proven TB, obstetric comorbidity and perinatal morbidity were similar in HIV-1-infected and non-infected mothers. VTRTB was detected in 16 newborns (16%), occurring similarly in bacteriologically-proven and suspected maternal TB disease, with no difference between HIV-1-infected and non-infected mothers. Eleven newborns with VTRTB were HIV-1 exposed; 64% acquired HIV-1 and died from rapidly progressive disease by 10 months of age. HIV-1-infected mothers and their exposed newborns had significantly lower CD4 counts. No association between perinatal maternal viral load, CD4 count or VTRTB was detected. CONCLUSION: Mothers with TB disease in pregnancy are at risk for significant perinatal morbidity, mortality and VTRTB.
Subject(s)
AIDS-Related Opportunistic Infections/transmission , Infectious Disease Transmission, Vertical/statistics & numerical data , Pregnancy Complications, Infectious/diagnosis , Pregnancy Outcome , Tuberculosis/transmission , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/epidemiology , Adolescent , Adult , Confidence Intervals , Developing Countries , Female , Humans , Incidence , Infant, Newborn , Mycobacterium tuberculosis/isolation & purification , Odds Ratio , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Prenatal Care , Probability , Risk Assessment , South Africa/epidemiology , Tuberculosis/diagnosis , Tuberculosis/epidemiologyABSTRACT
Although constant innovation has improved the performance of dentine adhesives, the true mechanism of resin adhesion to dentine is still not clear and the optimal dentinal surface pretreatment has yet to be determined for adhesive integrity of resin to dentine. The integrity of the collagen fibrils left exposed upon acid etching seem to play a major role in the mechanism of adhesion and intermingling of the adhesive monomers with the filigree of collagen fibers or hybrid layer should be considered the paramount dentine bonding mechanism. Definite trends are emerging but more research is necessary before general conclusions can be made about the functions of different bonding agents. The all-in-one self-etching/self-primer bottle systems are relatively new to the market and need more research before they can be advocated as the agent of choice.
Subject(s)
Dental Bonding , Dentin-Bonding Agents/chemistry , Dentin/ultrastructure , Acid Etching, Dental , Adhesiveness , Collagen/ultrastructure , Dental Leakage/classification , Dentin Permeability , Dentin-Bonding Agents/classification , Humans , Polymers/chemistry , Porosity , Smear Layer , Stress, Mechanical , Surface Properties , Water/chemistryABSTRACT
This study describes growth in a cohort of black South African children born to HIV-1-infected women in Durban. Children born to HIV-1-seropositive women were followed up from birth to early childhood. At birth and at each visit, growth parameters were measured. Mean Z-scores were calculated for weight-for-length, weight-for-age and length-for-age and, if they were low, the children were regarded as wasted, malnourished or stunted, respectively. At the end of the study, there were 48 infected and 93 uninfected children. There were no significant differences between the two groups at birth. Thereafter, the infected group was found to have early and sustained low mean Z-scores for length-for-age and weight-for-age but not for weight-for-length. The means reached significance at ages 3, 6 and 12 months for length and at 3, 6 and 9 months for weight. Infected children who died early had more severe stunting, wasting and malnutrition than infected children who survived. Infected children born to HIV-positive women have early and sustained stunting and are malnourished but not wasted. Children with rapidly progressive disease have both stunting and wasting and are more severely affected. Early nutritional intervention might help prevent early progression or death in HIV-infected children, particularly in developing countries without access to anti-retroviral therapy in state hospitals.
Subject(s)
Developing Countries , Growth Disorders/etiology , HIV Infections/complications , HIV-1 , Anthropometry , Body Height , Disease Progression , Female , Follow-Up Studies , Growth , Growth Disorders/physiopathology , HIV Infections/transmission , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Prognosis , Prospective Studies , Risk Factors , South Africa , Weight GainABSTRACT
Immunologic consequences of exposure to HIV-1 in utero are still poorly understood. This study investigates relationships between type-1 [interferon-gamma (IFN-gamma)] and type-2 (IL-10) cytokine production and maternal-infant HIV-1 transmission. Cord blood leukocytes from deliveries of 71 HIV-1-infected and 11 uninfected mothers were tested for in vitro IFN-gamma and IL-10 production after phytohemagglutinin (PHA) stimulation. The infants of these HIV-1-infected mothers were followed prospectively after birth to determine HIV vertical transmission, and IFN-gamma and IL-10 production was measured again at 6 mo. Median PHA-stimulated IFN-gamma production was 210 pg/mL in cord blood cells from infected and 73 pg/mL from uninfected mothers (p = 0.12), and median PHA-stimulated IL-10 production was 491 pg/mL in cord blood cells from infected and 161 pg/mL from uninfected mothers (p = 0.004). PHA-stimulated IFN-gamma and IL-10 production alone were not significantly associated with transmission, but relationships between the two cytokines differed among infected and uninfected infants of HIV-1-infected mothers. PHA-stimulated IFN-gamma and IL-10 production was positively correlated among infected (r = 0.7, p = 0.12 in cord blood and r = 0.66, p = 0.03 at 6 mo) but not uninfected infants, and stronger relative production of IFN-gamma to IL-10 was observed among exposed uninfected than among infected infants (p = 0.04). Exposure in utero to HIV-1 may augment production of IL-10 detectable in fetal cord blood. Stronger relative production of IFN-gamma to IL-10 in cord blood cells from infants of HIV-1-infected mothers may be associated with protection against perinatal HIV infection.
Subject(s)
HIV Infections/immunology , HIV-1 , Infectious Disease Transmission, Vertical , Interferon-gamma/blood , Interleukin-10/blood , Female , Fetal Blood/chemistry , HIV Infections/transmission , HIV Infections/virology , HIV-1/genetics , HIV-1/physiology , Humans , Infant, Newborn , Maternal Exposure , Phytohemagglutinins/pharmacology , RNA, Viral/blood , Randomized Controlled Trials as Topic , Viral LoadABSTRACT
A phase I, repeat-dose, open-label study was conducted to determine the pharmacokinetics and safety of zidovudine and lamivudine, coadministered orally every 12 hours, in 16 neonates whose mothers were infected with human immunodeficiency virus type 1 (HIV-1). The prospective mothers had been stabilized on a zidovudine/lamivudine regimen since week 36 of pregnancy to prevent mother-to-child transmission of HIV. During 1 week postpartum, the mothers received zidovudine 300 mg plus lamivudine 150 mg every 12 hours and breastfed. Neonatal treatment was initiated 12 hours following birth with 4 mg/kg of zidovudine suspension plus 2 mg/kg of lamivudine solution every 12 hours; this regimen was continued for 1 week. Between days 1 and 7 of neonatal treatment, the neonatal oral clearance (CL/F) of zidovudine and lamivudine increased by 2-fold (p < 0.001) and 1.6-fold (p = 0.004), respectively, possibly reflecting maturation of intestinal hepatic and renal function occurring during the first week of life. Day 7/day 1 ratios for exposure (area under the serum concentration-time curve [AUC]) and maximum observed serum concentration (Cmax) were 0.48 and 0.63, respectively, for zidovudine and 0.64 and 0.73, respectively, for lamivudine. At the time of delivery, the geometric mean cord/maternal concentration ratio was 1.24 for zidovudine and 1.12 for lamivudine, indicating free passage of each drug across the placenta. The maternal and neonatal treatment regimens were well tolerated. The results of this study confirm that in the neonate, a convenient regimen combining zidovudine 4 mg/kg and lamivudine 2 mg/kg, administered orally every 12 hours, provides zidovudine serum exposure very similar to that reported with the standard neonatal zidovudine regimen of 2 mg/kg every 6 hours, as well as lamivudine serum exposure within the range reported in adults receiving lamivudine 150 mg twice a day and children receiving 4 mg/kg twice a day.
Subject(s)
HIV-1 , Lamivudine/pharmacokinetics , Reverse Transcriptase Inhibitors/pharmacokinetics , Zidovudine/pharmacokinetics , Adult , Area Under Curve , Breast Feeding , Drug Combinations , Enzyme-Linked Immunosorbent Assay , Female , HIV Infections/prevention & control , HIV Infections/transmission , Half-Life , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Lamivudine/administration & dosage , Lamivudine/therapeutic use , Metabolic Clearance Rate , Pregnancy , RNA, Viral/isolation & purification , Reverse Transcriptase Inhibitors/administration & dosage , Reverse Transcriptase Inhibitors/therapeutic use , Viral Load , Zidovudine/administration & dosage , Zidovudine/therapeutic useABSTRACT
AIM: To describe a severe form of rapidly progressive HIV-1 infection manifesting in the neonatal period. METHOD: Prospective cohort study, King Edward VIII Hospital, Durban, South Africa. HIV-1-exposed neonates with hepatosplenomegaly, lymphadenopathy or persistent pneumonia within the first 28 days of life were investigated for perinatal infections. Confirmation of neonatal HIV-1 infection, HIV-1 subtype and clinical outcomes were studied. RESULTS: Twenty-three (72%) of 32 symptomatic HIV-1-exposed neonates recruited at a mean of 15.2 days were HIV-1-infected. HIV-1 infection was detected in 5 patients who were tested within 48 h of birth, confirming congenital infection. Congenital infection was not excluded in any case. Median neonatal viral load at recruitment was 471,932 copies/ml and median CD4 was 777 cells/mm3. The predominant clinical presentation was growth retardation and prematurity. Perinatal infections detected included: tuberculosis (8), syphilis (6) and cytomegalovirus (10). All of the neonates with perinatal tuberculosis were HIV-1-coinfected. Maternal and neonatal viral load and CD4 at recruitment were not statistically different between the groups with tuberculosis vs. other coinfections. Gag gene sequence analysis confirmed closely aligned HIV-1 subtype C in mothers and neonates. Nineteen (83%) died by 9 months, with a mean age at death of 3.5 months. CONCLUSIONS: A distinct group of HIV-1-infected babies may clinically manifest in the neonatal period with perinatal coinfections, subsequent rapidly progressive HIV-1 and early death.
Subject(s)
AIDS-Related Opportunistic Infections , HIV Infections/congenital , HIV Infections/physiopathology , HIV-1 , Cytomegalovirus Infections/complications , Developing Countries , HIV Infections/diagnosis , HIV Infections/transmission , HIV-1/genetics , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Prospective Studies , Syphilis/complications , Tuberculosis/complicationsABSTRACT
One of the major obstacles to the eradication of perinatal transmission of syphilis is the delay in obtaining the results of syphilis serological tests. The availability of on-site syphilis testing lead to this study which attempted to evaluate on-site syphilis testing performed by nursing staff. The seroprevalence of syphilis by laboratory rapid plasma reagin (RPR) was 8.2% (n=42). Twenty-one of the 42 women were correctly identified by the on-site test. The overall sensitivity of on-site testing was 50% [95% confidence interval (CI)=34.4-65.6]; specificity of 90.9% (95% CI=87.8-93.2). The on-site test correctly identified as uninfected 429 of the 471 women reported as RPR negative by the laboratory, giving a specificity of 91.1% (95% CI=88.1-93.4). The results of the study show that on-site RPR test had a sensitivity of 75% in respect of the clinically important titres of > or = 1:8. The specificity of the on-site test was 91.1% and on-site testing only failed to detect syphilis in those patients with titres of 1:1 and 1:2. On-site testing is a practical and cost-effective option to prevent congenital syphilis, in settings of a high prevalence of syphilis and using skilled testers.