Donor-derived human herpesvirus 8 and development of Kaposi sarcoma among 6 recipients of organs from donors with high-risk sexual and substance use behavior.

Kaposi sarcoma (KS) can develop following organ transplantation through reactivation of recipient human herpesvirus 8 (HHV-8) infection or through donor-derived HHV-8 transmission. We describe 6 cases of donor-derived HHV-8 infection and KS investigated from July 2018 to January 2020. Organs from 6 donors, retrospectively identified as HHV-8-positive, with a history of drug use disorder, were transplanted into 22 recipients. Four of 6 donors had risk factors for HHV-8 infection reported in donor history questionnaires. Fourteen of 22 organ recipients (64%) had evidence of posttransplant HHV-8 infection. Lung recipients were particularly susceptible to KS. Four of the 6 recipients who developed KS died from KS or associated complications. The US opioid crisis has resulted in an increasing number and proportion of organ donors with substance use disorder, and particularly injection drug use history, which may increase the risk of HHV-8 transmission to recipients. Better awareness of the risk of posttransplant KS for recipients of organs from donors with HHV-8 infection risk could be useful for recipient management. Testing donors and recipients for HHV-8 is currently challenging with no validated commercial serology kits available. Limited HHV-8 antibody testing is available through some US reference laboratories and the Centers for Disease Control and Prevention.

Epidemiology of cytomegalovirus Infection among mothers and infants in Colombia.

We assessed maternal and infant cytomegalovirus (CMV) infection in Colombia. Maternal serum was tested for CMV immunoglobulin G antibodies at a median of 10 (interquartile range: 8-12) weeks gestation (n = 1501). CMV DNA polymerase chain reaction was performed on infant urine to diagnose congenital (≤21 days of life) and postnatal (>21 days) infection. Maternal CMV seroprevalence was 98.1% (95% confidence interval [CI]: 97.5%-98.8%). Congenital CMV prevalence was 8.4 (95% CI: 3.9%-18.3%; 6/711) per 1000 live births. Among 472 infants without confirmed congenital CMV infection subsequently tested at age 6 months, 258 (54.7%, 95% CI: 50.2%-59.1%) had postnatal infection.

Urinary Cytomegalovirus Shedding in the United States: The National Health and Nutrition Examination Surveys, 1999-2004.

Background: There are no data on the prevalence of cytomegalovirus (CMV) shedding from a representative sample of the US population. This information is critical for understanding and preventing CMV. Methods: We tested urine specimens from CMV immunoglobulin (Ig) G-positive participants aged 6-49 years in 3 racial/ethnic groups from the National Health and Nutrition Examination Surveys 1999-2004 for the presence of CMV DNA using real-time polymerase chain reaction assay. We examined the association of sociodemographic characteristics with shedding prevalence and viral loads. Results: Among 6828 CMV IgG-positive participants tested, 537 had CMV DNA detected in urine-a shedding prevalence of 9.70%. Among persons aged 6-49 years, shedding prevalence was 3.83%. The prevalence of urinary shedding was inversely associated with increasing age (26.60%, 6.50%, and 3.45% in CMV IgG-positive participants aged 6-11, 12-19, and 20-49 years, respectively; P < .001 for trend test and pairwise comparisons). Urinary viral load also decreased significantly with age (mean, 2.97, 2.69, and 2.43 log10 copies/mL in those age groups, respectively; P < .001 for trend test and pairwise comparisons). Conclusions: Urinary CMV shedding and viral loads decreased dramatically with age, likely reflecting higher rates of primary CMV infection and longer duration of shedding in younger individuals. The findings demonstrate that children aged 6-11 years continue to shed CMV at higher rates and viral loads than adolescents and adults and thus may still be an important source for CMV transmission.

CMV on surfaces in homes with young children: results of PCR and viral culture testing.

BACKGROUND: Caring for young children is a known risk factor for cytomegalovirus (CMV) infection mainly through exposure to their saliva and urine. In a previous study, 36 CMV-seropositive children 2 mo. to 4 years old were categorized as CMV shedders (n = 23) or non-shedders (n = 13) based on detection of CMV DNA in their saliva and urine. The current study evaluated the presence of CMV on surfaces in homes of the children. METHODS: Study staff made 4 visits to homes of the 36 enrolled children over 100 days. Saliva was collected by swabbing the mouth and urine was collected on filter paper inserted into diapers. In addition, five surface specimens were collected: three in contact with children's saliva (spoon, child's cheek, washcloth) and two in contact with children's urine (diaper changing table, mother's hand). Samples were tested by PCR and viral culture to quantify the presence of CMV DNA and viable virus. RESULTS: A total of 654 surface samples from 36 homes were tested; 136 were CMV DNA positive, 122 of which (90%) were in homes of the children shedding CMV (p < 0.001). Saliva-associated samples were more often CMV positive with higher viral loads than urine-associated samples. The higher the CMV viral load of the child in the home, the more home surfaces that were PCR positive (p = 0.01) and viral culture positive (p = 0.05). CONCLUSIONS: The main source for CMV on surfaces in homes was saliva from the child in the home. Higher CMV viral loads shed by children correlated with more viable virus on surfaces which could potentially contribute to viral transmission.

Measurements of human herpesvirus 8 viral load in blood before and after leukoreduction filtration.

BACKGROUND: Human herpesvirus 8 (HHV-8) is likely transmitted through blood transfusion in high-prevalence areas. The efficacy of leukoreduction filtration for reducing HHV-8 in blood has not been reported. STUDY DESIGN AND METHODS: Blood was drawn from 45 human immunodeficiency virus-positive men either with Kaposi's sarcoma (KS; n=21) or without KS (n=24) and subject to leukoreduction filtration. HHV-8 viral load was measured in plasma and in blood before and after filtration. RESULTS: Twelve subjects, all with KS, had detectable HHV-8 viremia before filtration with viral loads of 10(2) to 10(5) copies/mL (mean, 3 × 10(4) copies/mL). After filtration, seven of 12 subjects no longer had detectable HHV-8 in their blood, and five of 12 subjects had detectable HHV-8 that was 90% reduced on average from prefiltration levels. The presence of HHV-8 in the blood after filtration was strongly associated with prefiltration viral loads greater than 1000 copies/mL and the presence of cell-free virus in plasma. None of the subjects without KS had detectable levels of HHV-8 virus in blood before or after filtration. CONCLUSION: Cell-associated HHV-8 appeared to be effectively removed by leukoreduction filtration. Cell-free HHV-8 was present in 42% of subjects as 1% to 20% of the total virus which was not removed by filtration.

Efficient linking of birth certificate and newborn screening databases for laboratory investigation of congenital cytomegalovirus infection and preterm birth: Florida, 2008.

The objectives of this study are (1) to design an accurate method for linking newborn screening (NBS) and state birth certificate databases to create a de-identified study database; (2) To assess maternal cytomegalovirus (CMV) seroprevalence by measuring CMV IgG in newborn dried blood spots; (3) To assess congenital CMV infection among newborns and possible association with preterm birth. NBS and birth databases were linked and patient records were de-identified. A stratified random sample of records based on gestational age was selected and used to retrieve blood spots from the state NBS laboratory. Serum containing maternal antibodies was eluted from blood spots and tested for the presence of CMV IgG. DNA was extracted from blood spots and tested for the presence of CMV DNA. Analyses were performed with bivariable and multivariable logistic regression models. Linkage rates and specimen collection exceeded 98% of the total possible yielding a final database with 3,101 newborn blood spots. CMV seroprevalence was 91% among Black mothers, 83% among Hispanic mothers, 59% among White mothers, and decreased with increasing amounts of education. The prevalence of CMV infection in newborns was 0.45% and did not vary significantly by gestational age. Successful methods for database linkage, newborn blood spots collection, and de-identification of records can serve as a model for future congenital exposure surveillance projects. Maternal CMV seroprevalence was strongly associated with race/ethnicity and educational level. Congenital CMV infection rates were lower than those reported by other studies and lacked statistical power to examine associations with preterm birth.

Sex and geographic patterns of human herpesvirus 8 infection in a nationally representative population­based sample in Uganda.

BACKGROUND: Human herpesvirus 8 (HHV8), the infectious cause of Kaposi sarcoma, varies dramatically across Africa, suggesting that cofactors correlated with large-area geographic or environmental characteristics may influence risk of infection. Variation in HHV8 seropositivity across small-area regions within countries in Africa is unknown. We investigated this issue in Uganda, where Kaposi sarcoma distribution is uneven and well described. METHODS: Archival samples from individuals aged 15-59 years randomly selected from a nationally representative 2004-2005 human immunodeficiency virus-AIDS serobehavioral survey were tested for HHV8 seropositivity with use of enzyme immunoassays based on synthetic peptides from the K8.1 and orf65 viral genes. Adjusted odds ratios and 95% confidence intervals (CIs) of association of HHV8 seropositivity with demographic risk factors were estimated. RESULTS: Among 2681 individuals tested, HHV8 seropositivity was 55.4%. HHV8 seropositivity was lower in female than in male persons (adjusted odds ratio, 0.82 [95% CI, 0.69-0.97]) and increased 2.2% (95% CI, 1.0%-3.6%) in female persons and 1.2% (95% CI, 1.0%-2.3%) in male persons per year of age. HHV8 seropositivity was inversely associated with education ( P = .01, for trend) and was elevated in the West Nile region, compared with the Central region (adjusted odds ratio, 1.49 [95% CI, 1.02-2.18]) but not with other regions. CONCLUSIONS: Our findings suggest that HHV8 seropositivity in Uganda may be influenced by cofactors correlated with small-area geography, age, sex, and education.

Detection of Cytomegalovirus in Urine Dried on Filter Paper.

Urine is the best specimen for the diagnosis of congenital cytomegalovirus, but collection and processing of liquid urine are impractical for screening. Urine dried on filter paper was processed by the same convenient, low-cost method used by newborn screening to test blood spots and showed high sensitivity and specificity.

Sensitivity of Dried Blood Spot Testing for Detection of Congenital Cytomegalovirus Infection.

Importance: The sensitivity of dried blood spots (DBS) to identify newborns with congenital cytomegalovirus (cCMV) infection has not been evaluated in screening studies using the current, higher-sensitivity methods for DBS processing. Objective: To assess the sensitivity of DBS polymerase chain reaction (PCR) for newborn screening for cCMV infection using saliva as the reference standard for screening, followed by collection of a urine sample for confirmation of congenital infection. Design, Setting, and Participants: This population-based cohort study took place at 5 newborn nurseries and 3 neonatal intensive care units in the Minneapolis/Saint Paul area in Minnesota from April 2016 to June 2019. Newborns enrolled with parental consent were screened for cCMV using DBS obtained for routine newborn screening and saliva collected 1 to 2 days after birth. Dried blood spots were tested for CMV DNA by PCR at both the University of Minnesota (UMN) and the US Centers for Disease Control and Prevention (CDC). Saliva swabs were tested by CMV DNA PCR at the UMN laboratory only. Newborns who screened positive by saliva or DBS had a diagnostic urine sample obtained by primary care professionals, tested by PCR within 3 weeks of birth. Analysis began July 2019. Exposures: Detection of CMV from a saliva swab using a PCR assay. Main Outcomes and Measures: Number of children with urine-confirmed cCMV and the proportion of them who were CMV positive through DBS screening. Results: Of 12 554 individuals enrolled through June 2019 (of 25 000 projected enrollment), 56 newborns were confirmed to have cCMV (4.5 per 1000 [95% CI, 3.3-5.7]). Combined DBS results from either UMN or CDC had a sensitivity of 85.7% (48 of 56; 95% CI, 74.3%-92.6%), specificity of 100.0% (95% CI, 100.0%-100.0%), positive predictive value (PPV) of 98.0% (95% CI, 89.3%-99.6%), and negative predictive value (NPV) of 99.9% (95% CI, 99.9%-100.0%). Dried blood spot results from UMN had a sensitivity of 73.2% (95% CI, 60.4%-83.0%), specificity of 100.0% (100.0%-100.0%), PPV of 100.0% (95% CI, 91.4%-100.0%), and NPV of 99.9% (95% CI, 99.8%-99.9%). Dried blood spot results from CDC had a sensitivity of 76.8% (95% CI, 64.2%-85.9%), specificity of 100.0% (95% CI, 100.0%-100.0%), PPV of 97.7% (95% CI, 88.2%-99.6%), and NPV of 99.9% (95% CI, 99.8%-99.9%). Saliva swab results had a sensitivity of 92.9% (52 of 56; 95% CI, 83.0%-97.2%), specificity of 99.9% (95% CI, 99.9%-100.0%), PPV of 86.7% (95% CI, 75.8%-93.1%), and NPV of 100.0% (95% CI, 99.9%-100.0%). Conclusions and Relevance: This study demonstrates relatively high analytical sensitivity for DBS compared with previous studies that performed population-based screening. As more sensitive DNA extraction and PCR methods continue to emerge, DBS-based testing should remain under investigation as a potential low-cost, high-throughput option for cCMV screening.

Use of screening dried blood spots for estimation of prevalence, risk factors, and birth outcomes of congenital cytomegalovirus infection.

OBJECTIVES: To determine the birth prevalence of cytomegalovirus (CMV) in a population-based sample of newborns by use of dried blood spots compared with previous studies that used established detection methods, and to evaluate risk factors and birth outcomes for congenital CMV infection. STUDY DESIGN: A total of 3972 newborn dried blood spots collected for the California Newborn Screening Program were tested for presence of CMV DNA. Demographic and pregnancy data were obtained from linked newborn screening and live-birth records. RESULTS: CMV prevalence among newborns by maternal race and ethnicity was 0.9% for blacks, 0.8% for Hispanics, 0.6% for whites, and 0.6% for Asians. Among Hispanics (n = 2053), infants who were infected had younger mothers (23 vs 26 years, P = .03), and prevalence was higher for children with no father information provided (2.6% vs 0.6%, P = .03). Overall CMV infection was associated with low birth weight (prevalence ratios [95% CI]: 3.4 [1.4-8.5]) and preterm birth (2.7 [1.4-5.1]). CMV viral loads were inversely related to birth weight and gestational age (both P = .03). CONCLUSIONS: CMV prevalence measured with dried blood spots was similar to reports using standard viral culture methods. Dried blood spots may be suitable for detection of CMV infection in newborns and warrant further evaluation. Congenital CMV infection may contribute to low birth weight and preterm birth.

Transmission of human herpesvirus 8 by blood transfusion.

BACKGROUND: Whether human herpesvirus 8 (HHV-8) is transmissible by blood transfusion remains undetermined. We evaluated the risk of HHV-8 transmission by blood transfusion in Uganda, where HHV-8 is endemic. METHODS: We enrolled patients in Kampala, Uganda, who had received blood transfusions between December 2000 and October 2001. Pretransfusion and multiple post-transfusion blood specimens from up to nine visits over a 6-month period were tested for HHV-8 antibody. We calculated the excess risk of seroconversion over time among recipients of HHV-8-seropositive blood as compared with recipients of seronegative blood. RESULTS: Of the 1811 transfusion recipients enrolled, 991 were HHV-8-seronegative before transfusion and completed the requisite follow-up, 43% of whom received HHV-8-seropositive blood and 57% of whom received seronegative blood. HHV-8 seroconversion occurred in 41 of the 991 recipients. The risk of seroconversion was significantly higher among recipients of HHV-8-seropositive blood than among recipients of seronegative blood (excess risk, 2.8%; P<0.05), and the increase in risk was seen mainly among patients in whom seroconversion occurred 3 to 10 weeks after transfusion (excess risk, 2.7%; P=0.005), a result consistent with the transmission of the virus by transfusion. Blood units stored for up to 4 days were more often associated with seroconversion than those stored for more than 4 days (excess risk, 4.2%; P<0.05). CONCLUSIONS: This study provides strong evidence that HHV-8 is transmitted by blood transfusion. The risk may be diminished as the period of blood storage increases.

Quantitation of human herpesvirus 8 (HHV-8) antibody in patients transfused with HHV-8-seropositive blood.

BACKGROUND: Human herpesvirus 8 (HHV-8) is endemic in Uganda where seroprevalence is approximately 40%. In a previous study, Ugandan patients receiving blood transfusions had multiple serum specimens collected for 6 months after transfusion to monitor for HHV-8 infection. It was observed that several HHV-8-seronegative patients were unexpectedly HHV-8 seropositive after blood transfusion. STUDY DESIGN AND METHODS: This study measured HHV-8 antibody in serially collected serum specimens from 542 patients who received transfusions and evaluated the risk of HHV-8 infection as a function of HHV-8 antibody levels in the donors. RESULTS: HHV-8 antibody was observed in 52% of patients transfused with HHV-8-seropositive blood in amounts that corresponded with their donor's antibody titer and waned within 40 days. Higher levels of passive HHV-8 antibody in patients who received transfusions appeared to be associated with a lower risk of HHV-8 infection. CONCLUSION: The source of transient antibody in patients who received transfusions was determined to be the transfused blood. Donors with higher HHV-8 antibody titers may have been less likely to have infectious virus in the blood.

The impact of maternal HIV and malaria infection on the prevalence of congenital cytomegalovirus infection in Western Kenya.

BACKGROUND: Data on congenital cytomegalovirus (CMV) infection in Africa are limited. OBJECTIVE: To describe the prevalence of congenital CMV infection in a population with high prevalence of maternal HIV and malaria infection in western Kenya. STUDY DESIGN: We screened newborns for CMV by polymerase chain reaction assay of saliva swabs and dried blood spots (DBS), and assessed maternal CMV immunoglobulin G (IgG) status by testing serum eluted from newborn's DBS. We calculated adjusted prevalence ratios (aPRs) using log-binomial regression models. RESULTS: Among 1066 mothers, 210 (19·7%) had HIV infection and 207 (19·4%) had malaria infection; 33 (3·1%) mothers had both. Maternal CMV IgG prevalence was 93·1% (95% confidence interval [CI]: 88·3%-96·0%). Among 1078 newborns (12 sets of twins), 39 (3·6%, 95% CI: 2·7-4·9%) were CMV positive. The prevalence of congenital CMV infection by maternal HIV and malaria infection status was 5·0% (95% CI: 2·7-9·2%) for HIV only, 5·1% (95% CI: 2·7-9·4%) for malaria only, 8·8 (95% CI: 3·1-23·0) for HIV and malaria co-infection, and 2·6% (95% CI: 1·7-4·1%) for none. Congenital CMV infection was independently associated with maternal HIV infection (aPR=2·1; 95% CI: 1·0-4·2), adjusting for maternal age, parity, and malaria infection. CONCLUSIONS: The prevalence of congenital CMV infection was higher than the 0·2-0·7% in developed countries. Maternal HIV infection may increase the risk of congenital CMV infection, but the role of maternal malaria on intrauterine transmission of CMV remains unclear.

Cohort study on maternal cytomegalovirus seroprevalence and prevalence and clinical manifestations of congenital infection in China.

Congenital cytomegalovirus (CMV) infection is the leading viral cause of birth defects and developmental disabilities in developed countries. However, CMV seroprevalence and burden of congenital CMV infection are not well defined in China.Cohort of newborns from 5 birthing hospitals in 2 counties of Shandong Province, China, were enrolled from March 2011 to August 2013. Dried blood spots (DBS) and saliva were collected within 4 days after birth for IgG testing for maternal seroprevalence and real-time PCR testing for congenital CMV infection, respectively.Among 5020 newborns tested for CMV IgG, 4827 were seropositive, resulting in CMV maternal seroprevalence of 96.2% (95% confidence interval [CI]:95.6%-96.7%). Of the 10,933 newborns screened for congenital CMV infection, 75 had CMV detected, resulting in an overall prevalence of 0.7% (95% CI: 0.5%-0.9%), with prevalences of 0.4% (14/3995), 0.6% (66/10,857), and 0.7% (52/7761) for DBS, wet saliva, and dried saliva specimens screened, respectively. Prevalence of congenital CMV infection decreased with increasing maternal age (0.9%, 0.6%, and 0.3% among newborns delivered from mothers aged 16-25, 26-35, and >35 years, respectively; P = 0.03), and was higher among preterm infants than full term infants (1.3% vs 0.6%, P = 0.04), infants with intrauterine growth restriction (IUGR) than those without (1.8% vs 0.7%, P = 0.03), and twins or triplets than singleton pregnancies (2.8% vs 0.7%, P = 0.04). None of the 75 newborns exhibited symptomatic congenital CMV infection, and there was no difference in clinical characteristics and newborn hearing screening results between infants with and without congenital CMV infection at birth.Congenital CMV infection prevalence was lower and the clinical manifestations were milder in this relatively developed region of China compared to populations from other countries with similarly high maternal seroprevalence. Follow-up on children with congenital CMV infection will clarify the burden of disabilities from congenital CMV infection in China.

Cytomegalovirus IgM Seroprevalence among Women of Reproductive Age in the United States.

Cytomegalovirus (CMV) IgM indicates recent active CMV infection. CMV IgM seroprevalence is a useful marker for prevalence of transmission. Using data from the National Health and Nutrition Examination Survey (NHANES) III 1988-1994, we present estimates of CMV IgM prevalence by race/ethnicity, provide a comparison of IgM seroprevalence among all women and among CMV IgG positive women, and explore factors possibly associated with IgM seroprevalence, including socioeconomic status and exposure to young children. There was no difference in IgM seroprevalence by race/ethnicity among all women (3.1%, 2.2%, and 1.6% for non-Hispanic white, non-Hispanic black and Mexican American, respectively; P = 0.11). CMV IgM seroprevalence decreased significantly with increasing age in non-Hispanic black women (P<0.001 for trend) and marginally among Mexican American women (P = 0.07), while no apparent trend with age was seen in non-Hispanic white women (P = 0.99). Among 4001 IgG+ women, 118 were IgM+, resulting in 4.9% IgM seroprevalence. In IgG+ women, IgM seroprevalence varied significantly by age (5.3%, 7.3%, and 3.7% for women of 12-19, 20-29, and 30-49 years; P = 0.04) and race/ethnicity (6.1%, 2.7%, and 2.0% for non-Hispanic white, non-Hispanic black, and Mexican American; P<0.001). The factors reported associated with IgG seroprevalence were not associated with IgM seroprevalence. The patterns of CMV IgM seroprevalence by age, race/ethnicity, and IgG serostatus may help understanding the epidemiology of congenital CMV infection as a consequence of vertical transmission and are useful for identifying target populations for intervention to reduce CMV transmission.

Seroprevalence of cytomegalovirus among children 1 to 5 years of age in the United States from the National Health and Nutrition Examination Survey of 2011 to 2012.

Cytomegalovirus (CMV) seroprevalence among U.S. children 1 to 5 years old was assessed in the National Health and Nutrition Examination Survey of 2011 to 2012. The overall seroprevalence (95% confidence interval) of IgG was 20.7% (14.4 to 28.2%), that of IgM was 1.1% (0.4 to 2.4%), and that of low IgG avidity was 3.6% (1.7 to 6.6%), corresponding to a 17.3% (10.1 to 26.7%) prevalence of recent infection among IgG-positive children.

Cytomegalovirus IgG Level and Avidity in Breastfeeding Infants of HIV-Infected Mothers in Malawi.

Cytomegalovirus (CMV) infection is common among infants of HIV-infected mothers in resource-limited settings. We examined the prevalence and timing of infant CMV infection during the first year of life using IgG antibody and avidity among HIV-exposed infants in Malawi and correlated the results with the presence of detectable CMV DNA in the blood. The Breastfeeding, Antiretrovirals and Nutrition (BAN) study randomized 2,369 mothers and their infants to maternal antiretrovirals, infant nevirapine, or neither for 28 weeks of breastfeeding, followed by weaning. Stored plasma specimens were tested for CMV IgG and antibody avidity from a random subset of infants who had been previously tested with blood CMV PCR and had available specimens at birth and at 24 and 48 weeks of age. Ninety-four of 127 infants (74.0%) tested at 24 weeks of age had CMV IgG of low or intermediate avidity, signifying primary CMV infections. An additional 22 infants (17.3%) had IgG of high avidity; 19 of them had CMV DNA detected in their blood, indicating infant infections. Taken together, these results show that the estimated prevalence of CMV infection at 24 weeks was 88.9%. By 48 weeks of age, 81.3% of infants had anti-CMV IgG; most of them (70.9%) had IgG of high avidity. The CMV serology and avidity testing, combined with the PCR results, confirmed a high rate of primary CMV infection by 6 months of life among breastfeeding infants of HIV-infected mothers. The CMV PCR in blood detected most, but not all, infant CMV infections.

Effect of cytomegalovirus infection on breastfeeding transmission of HIV and on the health of infants born to HIV-infected mothers.

BACKGROUND: Cytomegalovirus (CMV) infection can be acquired in utero or postnatally through horizontal transmission and breastfeeding. The effect of postnatal CMV infection on postnatal HIV transmission is unknown. METHODS: The Breastfeeding, Antiretrovirals and Nutrition study, conducted in Malawi, randomized 2369 mothers and their infants to three antiretroviral prophylaxis arms - mother (triple regimen), infant (nevirapine), or neither - for 28 weeks of breastfeeding, followed by weaning. Stored plasma and peripheral blood mononuclear cell specimens were available for 492 infants at 24 weeks and were tested with CMV PCR. Available samples from infants who were CMV PCR-positive at 24 weeks were also tested at birth (N = 242), and from infants PCR-negative at 24 weeks were tested at 48 weeks (N = 96). Cox proportional-hazards models were used to determine if CMV infection was associated with infant morbidity, mortality, or postnatal HIV acquisition. RESULTS: At 24 weeks of age, CMV DNA was detected in 345/492 infants (70.1%); the estimated congenital CMV infection rate was 2.3%, and the estimated rate of CMV infection at 48 weeks was 78.5%. CMV infection at 24 weeks was associated with subsequent HIV acquisition through breastfeeding or infant death between 24 and 48 weeks of age (hazard ratio 4.27, P = 0.05). CONCLUSION: Most breastfed infants of HIV-infected mothers in this resource-limited setting are infected with CMV by 24 weeks of age. Early CMV infection may be a risk factor for subsequent infant HIV infection through breastfeeding, pointing to the need for comprehensive approaches in order to achieve elimination of breastfeeding transmission of HIV.

Cytomegalovirus viral and antibody correlates in young children.

BACKGROUND: Young, healthy children shedding cytomegalovirus (CMV) in urine and saliva appear to be the leading source of CMV in primary infection of pregnant women. FINDINGS: We screened 48 children 6 months - 5 years old for CMV IgG and measured levels of CMV IgG, IgM and IgG avidity antibodies, frequency of CMV shedding, and viral loads in blood, urine, and saliva. Thirteen of the 48 children (27%) were CMV IgG positive, among whom 3 were also CMV IgM positive with evidence of recent primary infection. Nine of the 13 seropositive children (69%) were shedding 102-105 copies/ml of CMV DNA in one or more bodily fluid. Among seropositive children, low IgG antibody titer (1:20-1:80) was associated with the absence of shedding (p = 0.014), and enrollment in daycare was associated with the presence of CMV shedding (p = 0.037). CONCLUSIONS: CMV antibody profiles correlated with CMV shedding. The presence of CMV IgM more often represents primary infection in children than in adults. Correlating antibodies with primary infection and viral shedding in healthy children adds to the understanding of CMV infection in children that can inform the prevention of CMV transmission to pregnant women.

National prevalence estimates for cytomegalovirus IgM and IgG avidity and association between high IgM antibody titer and low IgG avidity.

Primary cytomegalovirus (CMV) infection of the mother during pregnancy presents risk of CMV infection of the fetus with resulting permanent disability. CMV IgM antibody is generated following primary CMV infection but also can appear during nonprimary CMV infection and is thus of limited diagnostic use by itself. In contrast, the presence of low CMV IgG avidity has been shown to be a unique and reliable serologic indicator of primary CMV infection. We measured CMV IgG and IgM antibody levels and IgG avidity in sera from a population sample of 6,067 U.S. women aged 12 to 49 years from NHANES (National Health and Nutrition Examination Survey). The CMV IgG prevalence was 58% overall and increased strongly with age. The CMV IgM prevalence was 3.0% overall and remained relatively flat across age groups. The prevalence of low IgG avidity was 2.0% overall, decreased sharply with age, and was seen mainly among IgM-positive sera. Fourteen to 18% of the CMV IgM-positive sera were low IgG avidity, presumably representing primary CMV infection. High CMV IgM antibody titer was a strong predictor of low IgG avidity. The ability to reliably identify primary CMV infection during pregnancy is important for management of the pregnancy, including possible treatment options for the fetus. Both IgM and IgG avidity measurements provide useful clinical information for evaluating primary CMV infection, although commercial tests for CMV IgG avidity are not yet widely available in the United States.