Soft X-Ray Second Harmonic Generation as an Interfacial Probe.

Nonlinear optical processes at soft x-ray wavelengths have remained largely unexplored due to the lack of available light sources with the requisite intensity and coherence. Here we report the observation of soft x-ray second harmonic generation near the carbon K edge (∼284 eV) in graphite thin films generated by high intensity, coherent soft x-ray pulses at the FERMI free electron laser. Our experimental results and accompanying first-principles theoretical analysis highlight the effect of resonant enhancement above the carbon K edge and show the technique to be interfacially sensitive in a centrosymmetric sample with second harmonic intensity arising primarily from the first atomic layer at the open surface. This technique and the associated theoretical framework demonstrate the ability to selectively probe interfaces, including those that are buried, with elemental specificity, providing a new tool for a range of scientific problems.

Double-configuration grating monochromator for extreme-ultraviolet ultrafast pulses.

We present the design and characterization of a double-configuration grating monochromator for the spectral selection of extreme-ultraviolet ultrafast pulses. Two grating geometries are joined in an instrument with two interchangeable diffracting stages, both used at grazing incidence: one with the gratings in the off-plane mount (OPM), the other in the classical diffraction mount (CDM). The use of two stages gives great flexibility: the OPM stage is used for sub-50 fs time response and low spectral resolution, while the CDM stage is for 100-200 fs time response and high spectral resolution. The monochromator spectral and temporal performances have been experimentally demonstrated on a high-order laser-harmonics beam line.

Tunable orbital angular momentum in high-harmonic generation.

Optical vortices are currently one of the most intensively studied topics in optics. These light beams, which carry orbital angular momentum (OAM), have been successfully utilized in the visible and infrared in a wide variety of applications. Moving to shorter wavelengths may open up completely new research directions in the areas of optical physics and material characterization. Here, we report on the generation of extreme-ultraviolet optical vortices with femtosecond duration carrying a controllable amount of OAM. From a basic physics viewpoint, our results help to resolve key questions such as the conservation of angular momentum in highly nonlinear light-matter interactions, and the disentanglement and independent control of the intrinsic and extrinsic components of the photon's angular momentum at short-wavelengths. The methods developed here will allow testing some of the recently proposed concepts such as OAM-induced dichroism, magnetic switching in organic molecules and violation of dipolar selection rules in atoms.

Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women.

BACKGROUND: Human papillomavirus (HPV) infection is associated with precancerous cervical squamous intraepithelial lesions commonly seen among women infected with human immunodeficiency virus-1 (HIV). We characterized HPV infection in a large cohort of HIV-positive and HIV-negative women participating in the Women's Interagency HIV Study to determine the prevalence of and risk factors for cervicovaginal HPV infection in HIV-positive women. METHODS: HIV-positive (n = 1778) and HIV-negative (n = 500) women were tested at enrollment for the presence of HPV DNA in a cervicovaginal lavage specimen. Blood samples were tested for HIV antibody status, level of CD4-positive T cells, and HIV RNA load (copies/mL). An interview detailing risk factors was conducted. Univariate and multivariate analyses were performed. RESULTS: Compared with HIV-negative women, HIV-positive women with a CD4+ cell count of less than 200/mm3 were at the highest risk of HPV infection, regardless of HIV RNA load (odds ratio [OR] = 10.13; 95% confidence interval [CI] = 7.32-14.04), followed by women with a CD4+ count greater than 200/mm3 and an HIV RNA load greater than 20,000 copies/mL (OR = 5.78; 95% CI = 4.17-8.08) and women with a CD4+ count greater than 200/mm3 and an HIV RNA load less than 20,000 copies/mL (OR = 3.12; 95% CI = 2.36-4.12), after adjustment for other factors. Other risk factors among HIV-positive women included racial/ethnic background (African-American versus Caucasian, OR = 1.64; 95% CI = 1.19-2.28), current smoking (yes versus no; OR = 1.55; 95% CI = 1.20-1.99), and younger age (age < 30 years versus > or = 40 years; OR = 1.75; 95% CI = 1.23-2.49). CONCLUSIONS: Although the strongest risk factors of HPV infection among HIV-positive women were indicators of more advanced HIV-related disease, other factors commonly found in studies of HIV-negative women, including racial/ethnic background, current smoking, and age, were important in HIV-positive women as well.

HIV-1 and pregnant women: associated factors, prevalence, estimate of incidence and role in fetal wastage in central Africa.

The major goals of this study were to measure the current prevalence and estimate the annual incidence of HIV-1 infection in young pregnant women from urban Malawi, to identify factors that were associated with HIV-1 infection, and to examine adverse pregnancy outcomes. Four hundred and sixty-one consecutive pregnant women were studied when they presented for prenatal care. The overall seroprevalence for HIV-1 infection in these urban populations was 17.6% (81 out of 461) during early 1989. Based on previous seroprevalence in similar unselected pregnant women, the estimated annual incidence of HIV-1 seroconversion in urban pregnant women ranged from 3 to 4% per annum between 1985 and 1987 and from 7 to 13% between 1987 and 1989. HIV-1 infection was significantly associated with reactive syphilis serology. Reported history of sexually transmitted disease was also correlated with HIV-1 infection but was not statistically significant. Other variables, such as history of transfusion, history of tuberculosis, parity or occupation were not associated with HIV-1 infection. History of spontaneous abortion was significantly associated with reactive syphilis serology, HIV-1 infection and history of sexually transmitted disease. In logistic regression analysis, HIV-1 infection remained the only significant variable that was correlated with spontaneous abortion. This study suggests that HIV-1 infection may play a role in fetal wastage.

Traditional vaginal agents: use and association with HIV infection in Malawian women.

OBJECTIVES: To assess the prevalence of traditional vaginal agent use in Malawian women and its association with HIV infection. METHODS: Consenting, consecutive antenatal women were administered a questionnaire and screened for sexually transmitted diseases (STD) including HIV. RESULTS: Of the 6603 consenting women, 886 (13%) reported using intravaginal agents for tightening and 2222 (34%) for self-treatment of vaginal discharge and itching. A higher proportion of HIV-infected than uninfected women (17% versus 14%) reported use of intravaginal agents for treatment (odds ratio, 1.29; 95% confidence interval, 1.05-1.57), but no difference in HIV status was found when these agents were used for tightening. In multivariate analysis, vaginal agent use for treatment was independently associated with HIV seropositivity. CONCLUSIONS: The association of HIV infection with vaginal agents for self-treatment, but not for tightening, suggests that STD may play a role or that vaginal agents are used differently for the two purposes. In addition to a small increased risk of HIV infection associated with vaginal agent use, these agents may interfere with condom effectiveness or acceptability of vaginal microbicides.

PIP: An exploratory study was conducted in Malawi to determine whether a correlation exists between human immunodeficiency virus (HIV) and traditional practices involving the intravaginal application of substances such as herbs and pulverized stone. Included in the survey were 6603 consecutive consenting volunteers who presented at the prenatal clinic of an urban hospital from October 1989-October 1990. The median age of study participants was 24 years. Although only 11% reported having had a sexually transmitted disease (STD) in the three years preceding the interview, laboratory analysis revealed the presence of such an infection in 46%. HIV infection was found in 1502 (23%). A total of 2953 (45%) of these pregnant women reported use of vaginal agents or vaginal incision, either for the treatment of discharge or itching or for the enhancement of sexual pleasure through vaginal tightening. Concerns have been raised that the placement of desiccants, irritants, and astringents in the vagina can induce certain physiological changes that increase the risk of HIV infection. Demonstrated in this survey was a slight association between HIV seropositivity and the use of vaginal agents for self-medication but not for vaginal tightening. In the univariate analysis, this finding persisted only for pregnant women without past or current STD infection. In the multivariate analysis, users of vaginal agents for treatment had a small increased risk of HIV in addition to--and independently of--the risk conferred by an STD history. It is possible, however, that the use of vaginal agents for self-medication is a marker for the presence of genital tract inflammation--a co-factor for HIV transmission. Given the extent of this traditional practice and its potential risk, more research is urged on the type of vaginal agents used and their effects on vaginal tissue.

Reported condom use is not associated with incidence of sexually transmitted diseases in Malawi.

OBJECTIVES: To establish frequency of reported condom use and validate reliability of self-reporting among urban women in Malawi. DESIGN: Cross-sectional survey in antenatal women in 1989 and 1993. Prospective study in cohort first surveyed in 1989. METHODS: A total of 6561 women in 1989 and 2460 women in 1993 answered questions about condom use and sexual activity, had a physical examination and were screened for HIV. A subset of women from the 1989 screening were administered a questionnaire and tested for syphilis, Neisseria gonorrhoeae and Trichomonas vaginalis infections every 6 months. RESULTS: Although between the two cross-sectional studies intermittent condom use increased from 6 to 15% (P < 0.001) with no difference according to HIV infection, consistent use was reported by less than 1%. In the prospective study, women reported a higher condom use at any visit than either group assessed cross-sectionally. Consistent condom use peaked at 62% in the first 6 months, but declined to as low as 8% in the second year of follow-up. Condom use at each visit, either intermittent or consistent, was higher in HIV-seropositive than HIV-seronegative women. Overall, the incidence of gonorrhea, trichomoniasis and syphilis did not decline in women reporting consistent condom use. CONCLUSIONS: In prospectively followed women reports of consistent condom use was substantially higher than in cross-sectional surveys, but rapidly decreased over time, irrespective of HIV status. The presence of new sexually transmitted diseases suggests that this population of urban women overreports condom use or underreports sexual activity, or both. Intensive and sustained education is needed to achieve consistent condom use. Biologic markers of sexual activity are useful in interpreting reported condom use.

PIP: To determine the frequency of reported condom use and validate the reliability of self-reporting among urban women in Malawi, 6561 women in 1989 and 2460 women in 1993 answered survey questions about condom use and sexual activity, had a physical examination, and were screened for HIV. A subset of women from the 1989 screening were administered a questionnaire and tested for syphilis, gonorrhea, and Trichomonas vaginalis infections every six months. The study populations consisted of consecutive women presenting for their first antenatal visit to Queen Elizabeth Hospital in Blantyre, Malawi. Intermittent condom use increased from 6% to 15% between the two cross-sectional studies, with no difference according to HIV infection; consistent condom use was reported by less than 1%. In the prospective study, women reported higher condom use at any visit than either group assessed cross-sectionally. Consistent condom use peaked at 62% in the first six months, but declined to as low as 8% during the second year of follow-up. Condom use at each visit, either intermittent or consistent, was higher among HIV-seropositive than HIV-seronegative women. Overall, the incidence of syphilis, gonorrhea, and trichomoniasis did not decline in women reporting consistent condom use. This incidence of new sexually transmitted diseases suggests that the studied population either overreports condom use or underreports sexual activity, or both.

Serum albumin as a predictor of survival in HIV-infected women in the Women's Interagency HIV study.

BACKGROUND: The level of serum albumin is associated with mortality in a wide variety of chronic diseases. However, few studies have examined the relationship between serum albumin and survival in HIV-1 infection. OBJECTIVES: To determine whether the serum albumin level is associated with survival in HIV-1 infected women. DESIGN: Prospective cohort study. Patients were interviewed and examined at 6 month intervals. SETTING: A North American multi-institutional cohort of HIV-infected women from five geographical areas. PARTICIPANTS: A total of 2056 HIV-infected women at various stages of disease. MEASUREMENTS: Mortality during the first 3 years of follow-up. The relative risk of death by serum albumin level was estimated using a proportional hazards ratio adjusted for CD4 cell count, HIV-1-RNA level and other relevant covariates. RESULT: Three year mortality for women in the lowest serum albumin category (< 35 g/l) was 48% compared with 11% in the highest category (> or = 42 g/l; P < 0.001). The adjusted relative hazard (RH) of death was 3.1 times greater for those in the lowest albumin category (P < 0.01). The excess risk associated with lower serum albumin levels remained when subjects with moderate to severe immunosuppression and abnormal kidney and liver function were excluded (P < 0.01). CONCLUSION: The baseline serum albumin level is an independent predictor of mortality in HIV-1-infected women. The serum albumin level may be a useful additional marker of HIV-1 disease progression, particularly among asymptomatic women with little or no evidence of immunosuppression.

Does umbilical cord blood polymerase chain reaction positivity indicate in utero (pre-labor) HIV infection?

OBJECTIVE: To compare risk factors for infants whose cord blood was positive for HIV DNA with those who were cord blood-negative but found to be HIV DNA-positive in early infancy. METHODS: In 1994, infants born to HIV-infected women were enrolled in a study in Blantyre, Malawi. Birth weight and transmission risk factors from cord blood-positive infants were compared with cord blood-negative/HIV-positive infants on their first postnatal visit (4-7 weeks of age). Testing for HIV DNA on cord and peripheral blood was performed by polymerase chain reaction. RESULTS: Of 249 HIV-infected infants (overall transmission rate, 26%), 83 (33%) were cord blood-positive and 166 were initially cord blood-negative. The mean birth weight was 2.1% (59 g) lighter in cord blood-positive infants than initially cord blood-negative infants; initially cord blood-negative infants were 2.8% (80 g) lighter than uninfected infants born to HIV-infected women. There were no significant differences in the risk factors for infection between HIV-infected cord blood-positive and -negative infants; when transmission was increased, both HIV-infected cord blood-positive and -negative infants contributed to the increase in a similar proportion. INTERPRETATION: It was concluded that umbilical cord blood positivity for HIV DNA did not identity a subset of in utero HIV-infected infants and suggested that HIV-infected cord blood-positive and -negative infants have similar timing and routes of HIV infection.

Trends of HIV-1 and sexually transmitted diseases among pregnant and postpartum women in urban Malawi.

OBJECTIVES: To examine rates of HIV-1 and sexually transmitted disease (STD) among pregnant and postpartum women in urban Malawi, Africa. DESIGN: Serial cross-sectional surveys and a prospective study. METHODS: Three major surveys were conducted in 1990, 1993 and 1994/1995. Consecutive first-visit antenatal women and women giving birth at the Queen Elizabeth Central Hospital were tested for HIV and STD after counseling and obtaining informed consent. Unlinked, anonymous HIV testing was also conducted on smaller samples of antenatal women in the same hospital to provide annual prevalence data. HIV-seronegative postpartum women from the 1990 and 1993 surveys were enrolled in a prospective study to determine HIV incidence. RESULTS: HIV seroprevalence rose from 2.0% in 1985 to 32.8% in 1996, a 16-fold increase. The highest age-specific HIV prevalence was in the following age-groups: 20-24 years during 1990, 25-29 years during 1993, and 30-34 years during 1996. Among 1173 women followed for a median of 30.9 months, HIV incidence was 5.98 per 100 person-years in women aged < 20 years and declined steadily in older women. The prevalence of STD significantly declined among both HIV-positive and negative women. This decline in STD prevalence, however, was not accompanied by increased condom use over time. CONCLUSIONS: Among urban childbearing women in Malawi, incidence of HIV is highest among young women while, currently, prevalence is highest among older women. Recent declines in STD prevalence suggest that HIV prevention programs are having an impact either through improved STD diagnosis and treatment or reduced risk behaviors. Sequential cross-sectional STD prevalence measures may be useful in monitoring effectiveness of STD and HIV prevention activities.

PIP: Prevalence rates of HIV-1 and other sexually transmitted diseases (STDs) among pregnant and postpartum women were investigated in sequential, cross-sectional studies (1990, 1993, and 1994-95) conducted at Queen Elizabeth Central Hospital in Blantyre, Malawi. Annual anonymous, unlinked testing revealed a linear increase in HIV-1 prevalence among antenatal patients from 2.0% in 1985 to 32.8% in 1996. Analysis of demographic attributes of women enrolled in the 1990 and 1993 surveys of consecutive, first-visit antenatal women (n = 6603 and 2161, respectively) and the 1994-95 study of all women giving birth at the hospital during a 6-month period (n = 6964) indicated that HIV-infected women were most likely to be young, with fewer pregnancies, and be more educated. The highest age-specific HIV prevalence shifted from 20-24 years in 1990 to 30-34 years in 1996, indicating an aging cohort of women who became infected at a younger age. Reported lifetime use of condoms increased from 5.6% in 1990 to 17.5% in 1993, then declined to 4.9% in 1995; condom use was consistently higher among HIV-positive than HIV-negative women. The prevalence of all STDs (syphilis, trichomoniasis, gonorrhea, and genital warts and ulcers) declined significantly during 1990-96, with the most consistent decreases recorded among HIV-positive women. In a follow-up study of 1173 HIV-seronegative, postpartum women evaluated for 2302 person-years (average duration, 30.9 months), 97 seroconverted (4.21/100 person-years). The seroconversion rate declined steadily from 21.26/100 person-years in 1990 to 1.11/100 person-years in 1994-95. These findings are consistent with those from other sub-Saharan African countries, indicating a rapid increase in HIV prevalence followed by stabilization within about 10 years of the onset of the epidemic. The large decline in STD prevalence in the antenatal population suggests that Malawi's national AIDS prevention program is having an impact, either through improved STD diagnosis and treatment or reduced risk behaviors.

Association of HIV-1 load and CD4 lymphocyte count with mortality among untreated African children over one year of age.

OBJECTIVE: To examine the association of viral load and CD4 lymphocyte count with mortality among HIV-infected children over one year of age. DESIGN: A prospective study. HIV-infected children were enrolled during the first year of life and followed for more than 2 years at the Queen Elizabeth Central Hospital in Blantyre, Malawi (southeast Africa). METHODS: Morbidity and mortality information was collected every 3 months, and physical examination and blood testing (for viral level and CD4 cell percentage) were performed every 6 months. Kaplan-Meier analyses and proportional hazards models were used to estimate survival and to examine the association of primary predictors with mortality. RESULTS: Of 155 HIV-infected children originally enrolled, 115 (74%) had viral load testing and 82 (53%) had both viral load and CD4 cell percentage testing after their first year. Among children over one year of age, significant associations were found between mortality and the log10 viral load and CD4 cell percentage in both univariate and multivariate models. Independent of the CD4 cell value, a one unit log10 increase in HIV RNA level increased the hazard of child mortality by more than twofold. Children with low CD4 cell counts (< 15%) and high viral loads (> or = 250,000 copies/ml median value) had the worst survival; children with high CD4 cell counts (> or = 15%) and low viral loads (< 250,000 copies/ml) had the best survival. CONCLUSION: As in developed countries, viral load and CD4 cell count are the main predictors of mortality among African children. Making these tests available adds to the challenges to be considered if antiviral therapies were to be adopted in these countries.

Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV.

BACKGROUND: Cross-sectional studies suggest an association between bacterial vaginosis (BV) and HIV-1 infection. However, an assessment of a temporal effect was not possible. OBJECTIVES: To determine the association of BV and other disturbances of vaginal flora with HIV seroconversion among pregnant and postnatal women in Malawi, Africa. DESIGN: Longitudinal follow-up of pregnant and postpartum women. METHODS: Women attending their first antenatal care visit were screened for HIV after counselling and obtaining informed consent. HIV-seronegative women were enrolled and followed during pregnancy and after delivery. These women were again tested for HIV at delivery and at 6-monthly visits postnatally. Clinical examinations and collection of laboratory specimens (for BV and sexually transmitted diseases) were conducted at screening and at the postnatal 6-monthly visits. The diagnosis of BV was based on clinical criteria. Associations of BV and other risk factors with HIV seroconversion, were examined using contingency tables and multiple logistic regression analyses on antenatal data, and Kaplan-Meier proportional hazards analyses on postnatal data. RESULTS: Among 1196 HIV-seronegative women who were followed antenatally for a median of 3.4 months, 27 women seroconverted by time of delivery. Postnatally, 97 seroconversions occurred among 1169 seronegative women who were followed for a median of 2.5 years. Bacterial vaginosis was significantly associated with antenatal HIV seroconversion (adjusted odds ratio = 3.7) and postnatal HIV seroconversion (adjusted rate ratio = 2.3). There was a significant trend of increased risk of HIV seroconversion with increasing severity of vaginal disturbance among both antenatal and postnatal women. The approximate attributable risk of BV alone was 23% for antenatal HIV seroconversions and 14% for postnatal seroconversions. CONCLUSIONS: This prospective study suggests that progressively greater disturbances of vaginal flora, increase HIV acquisition during pregnancy and postnatally. The screening and treating of women with BV could restore normal flora and reduce their susceptibility to HIV.

Preparations for AIDS vaccine evaluations. Rate of new HIV infection in a cohort of women of childbearing age in Malawi.

PIP: Women attending the Queen Elizabeth Central Hospital in Blantyre, Malawi, between November 1989 and October 1993 were studied as part of a longitudinal cohort study of mother-to-infant HIV transmission. 694 HIV-seropositive and 687 HIV-seronegative women were enrolled at delivery. In the follow-up phase, women attended the clinic every 3 months for the first 24 months and every 6 months thereafter, where they were administered a questionnaire and underwent pelvic exam for the diagnosis of sexually transmitted diseases. HIV testing was performed by ELISA and Western Blotting. A nested case-control study was performed to identify risk factors for HIV seroconversion, and for each seroconverter, 2 seronegative women were selected. A total of 43 women seroconverted in the follow-up period. The rate of new HIV infection increased in the first 24 months postpartum. Postpartum rates were 1.42, 1.70, 2.43, and 4.33 per 100 person-semesters, respectively, in each of the first 4 semesters, which corresponded to annual seroconversion rates of 2.84 per 100 person-years in the 1st year and 6.66 in the 2nd year postpartum. Only 2.2% of the women reported sexual contact in the first 6 weeks postpartum, increasing to 57.6% in the period of 6 weeks to 6 months and to 86.5% in the period 7-12 months postpartum. Univariate analysis indicated the largest risk factor for HIV seroconversion as reported condom use (odds ratio [OR] = 5.67). Other factors included young age and low parity (OR = 2.90 and 2.77, respectively), a short interval between the birth of the study infant and a subsequent conception (OR = 4.20), and vaginal infection with Trichomonas vaginalis (OR = 3.4). Other factors with nonsignificant association with HIV seroconversion included: 1) genital ulcerations with a fourfold higher risk, 2) visible genital warts with a threefold increase, 3) hormone-containing contraceptives and cervical ectopy (OR = 1.13 and 1.07, respectively), and 4) vaginal irritants. Syphilis, cervical human papilloma virus, and cervical gonococcal infection were not associated with HIV seroconversion.^ieng

Factors associated with incident self-reported AIDS among women enrolled in the women's interagency HIV study (WIHS). WIHS Collaboratorive Study Group.

We evaluated factors associated with incident self-reported AIDS diagnoses among HIV-infected women in the Women's Interagency HIV Study (WIHS). Baseline information included age, race/ethnicity, HIV risk category, site of enrollment, years of education, cigarette smoking, CD4 cell count, and HIV viral load. Baseline and follow-up data on self-reported AIDS were analyzed using chi-square, Kaplan-Meier, and Cox proportional hazard models. Among the 1397 HIV-infected women who reported being free of clinical AIDS at baseline, 335 women (24%) reported an incident AIDS diagnosis during follow-up. In stratified Kaplan-Meier analyses, the development of self-reported AIDS was significantly associated with baseline CD4 cell count and viral load (p<0.01). In multivariate Cox proportional hazard analyses, women were statistically more likely to report AIDS if they had CD4 cell counts below 195 cells/mm3 (p<0.01), HIV RNA >4000 copies/ml (p<0.01), were current smokers (p<0.01), and had "no identifiable risk" for acquisition of HIV (p = 0.03). Self-reports of a clinical AIDS diagnosis may not always be accurate, but laboratory markers of HIV disease indicate that those women who self-report such diagnoses have greater immunodeficiency and a higher viral load when compared with those who report no AIDS-defining diagnoses.

V3 loops of HIV-1 specimens from pregnant women in Malawi uniformly lack a potential N-linked glycosylation site.

PIP: The HIV-1 env gene was amplified from the peripheral blood mononuclear cells of 14 infected pregnant women in Malawi. Nested polymerase chain reaction (PCR) and DNA sequencing were performed. The PCR product was purified and the C2-V3 region sequenced. Using the similarity function of the multiple aligned sequence editor, 13 of the nucleotide sequences were compared. The interperson variation, based on single base substitutions, ranged from 7.3 to 22.2% (mean 13.6%). All of the sequences showed the tetrapeptide motif at the crown of the V3 loop which is commonly seen among HIV-1 subtypes A, C, D, and E. The C2-V3 coding sequences clustered with the subtype C sequence reported from South Africa. In addition, all of these sequences lacked a potential N-linked glycosylation site found in all HIV-1 sequences except subtype C. In these specimens, the predominant replacement was valine. The role of this site in HIV-1 transmission is controversial.^ieng

Mortality after the first year of life among human immunodeficiency virus type 1-infected and uninfected children.

BACKGROUND: HIV-infected and uninfected children who survived their first year of life were prospectively followed in Malawi to assess levels of mortality and related risk factors during the second and third years of life. METHODS: Children with known HIV status from an earlier perinatal intervention trial were enrolled. These children [HIV-infected (Group A); HIV-uninfected but born to HIV-seropositive mothers (Group B); and children born to HIV-seronegative mothers (Group C)] were followed every 3 months until age 36 months. Mortality data were collected at each visit. Immunologic data (CD4+ percent) were collected at or immediately after enrollment. RESULTS: Overall 702 children were enrolled and 83 children died during follow-up. The mortality rate per 1000 person years of observation was 339.3 among Group A children, 46.3 among Group B children and 35.7 among Group C children. Among HIV-infected children the cumulative proportion surviving to age 24 months was 70% and those surviving to age 36 months was 55%. By age 32 months none of the severely immunosuppressed (CD4% < 15%) children had survived. The mortality differentials between HIV-infected and uninfected children persisted after adjusting for several risk factors. The major causes of death among infected children (n = 52) were wasting and respiratory conditions. CONCLUSIONS: Although all HIV-infected children had received childhood immunizations, mortality was high. Management of these children should include aggressive antimicrobial treatment, and evaluation of prophylactic regimens should be considered.

A retrospective study of childhood mortality and spontaneous abortion in HIV-1 infected women in urban Malawi.

HIV infection in pregnant women has been shown to have an adverse effect on the fetus and newborn. We undertook this study to examine the adverse effect of maternal HIV-1 infection on two outcomes of the previous pregnancy, as reported by the women: childhood mortality under the age of 3 years and spontaneous abortion. Some 6605 consecutive women who presented to a large urban hospital in Malawi for antenatal care were interviewed and tested for HIV-1 antibody. Of these 4229 (64%) were multiparous and 833 (19.7%) were seropositive for HIV-1. A history of under-3 mortality of the previous pregnancy was more common in HIV-1 seropositive than HIV-1 seronegative women (35% versus 15%, P less than 0.001). In the previous pregnancy, death of infants and children under 3 years was 77 and 119 per 1000 respectively for HIV-1 seronegative mothers, but increased to 171 and 292 per 1000 in infants and children under 3 years for HIV-1 seropositive mothers. History of child mortality was independently associated with positive HIV-1 serology, positive syphilis serology, low socioeconomic status, young age and not having married. There was no correlation between history of child mortality and reported symptoms of HIV/AIDS by infected mothers, except for history of tuberculosis which was reported more often by mothers whose child had died (4% versus 1%, P less than 0.036).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of human immunodeficiency virus infection on birthweight, and infant and child mortality in urban Malawi.

BACKGROUND: Low birthweight, prematurity and intra-uterine growth retardation (IUGR) are major determinants of child survival. Therefore, it is important to assess excess mortality due to human immunodeficiency virus (HIV) infection in populations where low birthweight is common. METHODS: A prospective study was conducted on 1385 children born to seropositive and seronegative women in urban Malawi. Children were regularly examined and tested for HIV. RESULTS: The mortality rate of children of HIV seropositive mothers was substantially higher (223/1000 at 12 months, 317/1000 at 24 months and 360/1000 at 30 months) than that of children of seronegative mothers (68/1000 at 12 months, 106/1000 at 24 months and 118/1000 at 30 months). The incidence of prematurity and IUGR was also higher in infants of HIV seropositive mothers than in infants of seronegative mothers (12.7% versus 3.8%, P < 0.001 for premature and 7.7% versus 4.4%, P = 0.02 for IUGR infants). The mother-to-infant HIV-1 transmission rate was 35.1%. After 12 months of age, HIV infected children showed the highest mortality; however, uninfected children of HIV seropositive and children of HIV seronegative mothers had similar mortality. The mean birthweight of HIV infected and uninfected children was not significantly different. In HIV infected children the most frequent causes of death were diarrhoea, pneumonia and failure to thrive. Less common risk factors for child mortality included active maternal syphilis and cervicitis/vaginitis. CONCLUSION: The substantial difference in survival among children of HIV infected and uninfected mothers suggests that mortality could be reduced if HIV infection were not a risk factor. To decrease childhood mortality, a combination of interventions such as treatment of sexually transmitted infections during pregnancy and measures to reduce mother-to-infant transmission should be adopted.

PIP: Low birth weight, prematurity, and intra-uterine growth retardation (IUGR) are major determinants of child survival. Therefore, it is important to assess excess mortality due to human immunodeficiency virus (HIV) infection in populations where low birth weight is common. A prospective study was conducted on a total of 1385 children born to 679 HIV-seropositive and 687 seronegative women in urban Malawi. Children were regularly examined and tested for HIV. The mortality rate of children of HIV-seropositive mothers was substantiality higher (223/1000 at 12 months, 317/1000 at 24 months, and 360/1000 at 30 months, p 0.0001) than that of children of seronegative mothers (68/1000 at 12 months, 106/1000 at 24 months, and 118/1000 at 30 months). The incidence of prematurity and IUGR was also higher in infants of HIV-seropositive mothers than in infants of seronegative mothers (12.5% versus 3.8%, p 0.001 for premature and 7.7% versus 4.4%, p = 0.02 for IUGR infants). The mother-to-infant HIV-1 transmission rate was 35.1%. The overall incidence of low birth weight was 14.1%, but the incidence was 20.1% among children of seropositive mothers and 8.3% among those of seronegative mothers (p 0.001). After 12 months of age, HIV-infected children showed the highest mortality; however, uninfected children of HIV-seropositive and children of HIV-seronegative mothers had similar mortality. The mean birth weight of HIV-infected and uninfected children was not significantly different. In HIV-infected children the most frequent causes of death were diarrhea, pneumonia, and failure to thrive. Less common risk factors for child mortality included active maternal syphilis and cervicitis/vaginitis. A possible enrolment bias could have resulted in lower mortality estimates among babies of HIV-seronegative mothers. To decrease childhood mortality, a combination of interventions such as treatment of sexually transmitted infections during pregnancy and measures to reduce mother-to-infant transmission should be adopted.

Predictors and impact of losses to follow-up in an HIV-1 perinatal transmission cohort in Malawi.

BACKGROUND: Large simple trials which aim to study therapeutic interventions and epidemiological associations of human immunodeficiency virus (HIV) infection, including perinatal transmission, in Africa may have substantial rates of loss to follow-up. A better understanding of the characteristics and the impact of women and children lost to follow-up is needed. METHODS: We studied predictors and the impact of losses to follow-up of infants born in a large cohort of delivering women in urban Malawi. The cohort was established as part of a trial of vaginal cleansing with chlorhexidine during delivery to prevent mother-to-infant transmission of HIV. RESULTS: The HIV infection status could not be determined for 797 (36.9%) of 2156 infants born to HIV-infected mothers; 144 (6.7%) with missing status because of various sample problems and 653 (30.3%) because they never returned to the clinic. Notably, the observed rates of perinatal transmission were significantly lower in infants who returned later for determination of their infection status (odds ratio = 0.94 per month, P = 0.03), even though these infants must have had an additional risk of infection from breastfeeding. In multivariate models, infants of lower birthweight (P = 0.003) and, marginally, singletons (P = 0.09) were less likely to return for follow-up. The parents of infants lost to follow-up tended to be less educated (P < 0.001) and more likely to be in farming occupations, although one educated group, teachers and students, were also significantly less likely to return. Of these variables, infant birthweight, twins versus singletons, and maternal education were also associated with significant variation in the observed risk of perinatal transmission among infants of known HIV status. CONCLUSIONS: Several predictors of loss to follow-up were identified in this large HIV perinatal cohort. Losses to follow-up can impact the observed transmission rate and the risk associations in different studies.

PIP: Predictors and the impact of losses to follow-up of infants born to a large HIV- infected cohort of delivering women in urban Malawi were studied. The women enrolled in an intervention trial including vaginal cleansing with chlorhexidine at the time of delivery. Findings showed that of the 2156 infants born to HIV- infected mothers, about 1359 (63.1%) had been diagnosed with HIV infection, 797 (36.9%) with undetermined status, 144 (6.7%) with missing status, and about 653 (30.3%) were never brought back for follow-up. The odds of HIV positivity decreased in the determination of infectious status (P = 0.03) despite the probability of additional transmission from breast-feeding. Late-coming and lost children of less educated parents had similar birth weight (P = 0.50) and were likely less to return. This was probably due to the fact that the fathers of the lost children were farmers. Besides, infant birth weight, twins vs. singletons, and maternal education were affiliated with significant variation in the observed risk of perinatal transmission among HIV-positive infants. Thus, with regard to the intervention trial, the LFU were approximately equal in both groups. There was no evidence that the losses were unbalanced between arms in relation to the predictors of transmission.

Childhood malaria parasitaemia and human immunodeficiency virus infection in Malawi.

PIP: Malaria and human immunodeficiency virus (HIV) infection are major health problems in many areas in Sub-Saharan Africa. An interaction between malaria and HIV infection has been postulated, since both produce similar cellular immune responses, with a lowering of the CD4/CD8 lymphocyte ratio. The frequency of malaria parasitemia was examined in children born to HIV-seropositive and seronegative mothers attending regular postnatal visits. A prospective study on mother-to-infant transmission of HIV had been underway since 1989 in Queen Elizabeth Central Hospital, Blantyre, a major hospital in urban Malawi. Standard HIV serology was performed on pregnant women, after obtaining consent. To reduce the effect of selection bias and seasonality, HIV seropositive (case) and seronegative (control) mothers and their infants were enrolled at delivery. Children included in the study were 503 born to 494 HIV-seropositive mothers and 540 born to 536 HIV-seronegative mothers. At each 3-monthly postpartum visit a Giemsa-stained thick blood film from the child was examined for malaria parasites. Children born to HIV-seropositive mothers were tested for HIV antibodies at 12 and 18 months of age. Of the 353 children born to HIV-seropositive mothers, 82 children (23.2%) were found to be HIV seropositive by enzyme-linked immunosorbent assay and Western blotting at 12 and 18 months. No statistically significant difference was found in frequency of malaria parasitemia by maternal or infant HIV serostatus after controlling for child's age. There was, however, a significant trend of increase in high parasitemia with age, irrespective of the HIV serostatus of the mother or the child. The frequency of parasitemia was higher in the wet season than in the dry season. This study suggests that maternal or infant HIV infection does not alter susceptibility to, or the clinical course of, malaria in infants.^ieng