Herpes Mastitis: Diagnosis and Management.

Herpetic lesions most frequently occur on oral and genital areas. However, herpes simplex virus (HSV) can be a rare cause of breast infection. In few published articles, the route of transmission is predominantly from infant to mother. We report two cases about simultaneous mammary and extramammary (oral and genital) herpetic infection in nonlactating women. In both cases, HSV breast lesions were acquired by sexual contacts with partners who were asymptomatic HSV carriers. Through a review of literature, we highlight clinical signs for an early diagnosis. We also emphasize the advantage of the valacyclovir for treating this uncommon pathology.

Postnatal cytomegalovirus exposure in infants of antiretroviral-treated and untreated HIV-infected mothers.

HIV-1 and CMV are important pathogens transmitted via breastfeeding. Furthermore, perinatal CMV transmission may impact growth and disease progression in HIV-exposed infants. Although maternal antiretroviral therapy reduces milk HIV-1 RNA load and postnatal transmission, its impact on milk CMV load is unclear. We examined the relationship between milk CMV and HIV-1 load (4-6 weeks postpartum) and the impact of antiretroviral treatment in 69 HIV-infected, lactating Malawian women and assessed the relationship between milk CMV load and postnatal growth in HIV-exposed, breastfed infants through six months of age. Despite an association between milk HIV-1 RNA and CMV DNA load (0.39 log(10) rise CMV load per log(10) rise HIV-1 RNA load, 95% CI 0.13-0.66), milk CMV load was similar in antiretroviral-treated and untreated women. Higher milk CMV load was associated with lower length-for-age (-0.53, 95% CI: -0.96, -0.10) and weight-for-age (-0.40, 95% CI: -0.67, -0.13) Z-score at six months in exposed, uninfected infants. As the impact of maternal antiretroviral therapy on the magnitude of postnatal CMV exposure may be limited, our findings of an inverse relationship between infant growth and milk CMV load highlight the importance of defining the role of perinatal CMV exposure on growth faltering of HIV-exposed infants.

Sheep with scrapie and mastitis transmit infectious prions through the milk.

Prions are misfolded proteins that are infectious and naturally transmitted, causing a fatal neurological disease in humans and animals. Prion shedding routes have been shown to be modified by inflammation in excretory organs, such as the kidney. Here, we show that sheep with scrapie and lentiviral mastitis secrete prions into the milk and infect nearly 90% of naïve suckling lambs. Thus, lentiviruses may enhance prion transmission, conceivably sustaining prion infections in flocks for generations. This study also indicates a risk of prion spread to sheep and potentially to other animals through dietary exposure to pooled sheep milk or milk products.

Genetic analyses of HIV-1 env sequences demonstrate limited compartmentalization in breast milk and suggest viral replication within the breast that increases with mastitis.

The concentration of human immunodeficiency virus type 1 (HIV-1) is generally lower in breast milk than in blood. Mastitis, or inflammation of the breast, is associated with increased levels of milk HIV-1 and risk of mother-to-child transmission through breastfeeding. We hypothesized that mastitis facilitates the passage of HIV-1 from blood into milk or stimulates virus production within the breast. HIV-1 env sequences were generated from single amplicons obtained from breast milk and blood samples in a cross-sectional study. Viral compartmentalization was evaluated using several statistical methods, including the Slatkin and Maddison (SM) test. Mastitis was defined as an elevated milk sodium (Na(+)) concentration. The association between milk Na(+) and the pairwise genetic distance between milk and blood viral sequences was modeled using linear regression. HIV-1 was compartmentalized within milk by SM testing in 6/17 (35%) specimens obtained from 9 women, but all phylogenetic clades included viral sequences from milk and blood samples. Monotypic sequences were more prevalent in milk samples than in blood samples (22% versus 13%; P = 0.012), which accounted for half of the compartmentalization observed. Mastitis was not associated with compartmentalization by SM testing (P = 0.621), but Na(+) was correlated with greater genetic distance between milk and blood HIV-1 populations (P = 0.041). In conclusion, local production of HIV-1 within the breast is suggested by compartmentalization of virus and a higher prevalence of monotypic viruses in milk specimens. However, phylogenetic trees demonstrate extensive mixing of viruses between milk and blood specimens. HIV-1 replication in breast milk appears to increase with inflammation, contributing to higher milk viral loads during mastitis.

Associations between breast milk viral load, mastitis, exclusive breast-feeding, and postnatal transmission of HIV.

BACKGROUND: . Exclusive breast-feeding is protective against postnatal transmission of human immunodeficiency virus (HIV), compared with mixed breast-feeding. Accordingly, exclusive breast-feeding for 6 months is the World Health Organization's recommendation to HIV-infected mothers for whom exclusive replacement feeding is not acceptable, feasible, affordable, safe, or sustainable. The mechanism of exclusive breast-feeding protection is unknown but is hypothesized to be mediated through reduced mastitis. METHODS: We compared breast milk and plasma specimens of exclusive breast-feeding and mixed breast-feeding HIV- positive mothers archived from the ZVITAMBO trial in which mixed breast-feeding was associated with a 2-fold increased risk of postnatal transmission at 18 months. Plasma HIV load, breast milk HIV load and sodium/potassium ratio were measured as a proxy for subclinical mastitis. RESULTS: Mixed breast-feeding was not associated with mastitis or breast milk HIV load. Mastitis was associated with breast milk HIV load, and this effect increased with increasing maternal plasma HIV load; mastitis was associated with postnatal transmission only when maternal plasma HIV load was high (>3.7 log(10) copies/mL). Initiation of breast-feeding within an hour of delivery was associated with exclusive breast-feeding (adjusted odds ratio, 1.62; 95% confidence interval, 1.02-2.58). CONCLUSIONS: Exclusive breast-feeding is associated with reduced postnatal transmission of HIV from mother to child, but this protection is not mediated by reduced mastitis or breast milk HIV load. The deleterious effect of mastitis increases as the mother's plasma HIV load increases.

Increased Epstein-Barr virus in breast milk occurs with subclinical mastitis and HIV shedding.

Epstein-Barr virus (EBV) in breast milk and subclinical mastitis (SCM) are both associated with human immunodeficiency virus (HIV) shedding and possibly with postnatal HIV transmission. The objective of this nested case-control study was to investigate the interplay between SCM and EBV replication in breast milk of HIV-infected mothers.The relationships between EBV deoxyribonucleic acid (DNA) shedding, HIV-1 ribonucleic acid (RNA) level, and SCM were explored in breast milk samples of Zambian mothers participating in the ANRS 12174 trial. Mammary gland inflammation was defined as a breast milk sodium to potassium ratio (Na/K) greater than 0.6 and further subclassified as either "possible SCM" (Na/K ratio 0.6-1.0) or SCM (Na/K ratio ≥ 1.0). Breast milk interleukin 8 (IL-8) was measured as a surrogate marker of mammary gland inflammation.EBV DNA was detected in breast milk samples from 42 out of 83 (51%) participants and was associated with HIV-1 shedding in breast milk (P = 0.006). EBV DNA levels were higher in samples with SCM and "possible SCM" compared to non-SCM breast milk samples (P = 0.06; P = 0.007). An EBV DNA level of >200 copies/mL was independently associated with SCM and "possible SCM" (OR: 2.62; 95%: 1.13-6.10). In patients with SCM, higher EBV replication in the mammary gland was associated with a lower induction of IL-8 (P = 0.013). Resistance to DNase treatment suggests that EBV DNA in lactoserum is encapsidated.SCM and decreased IL-8 responses are associated with an increased EBV shedding in breast milk which may in turn facilitate HIV replication in the mammary gland.

Vitamin A, mastitis, and mother-to-child transmission of HIV-1 through breast-feeding: current information and gaps in knowledge.

Mastitis has been implicated as a risk factor for mother-to-child transmission (MTCT) of HIV-1 through breast-feeding. Maternal vitamin A deficiency is also associated with increased MTCT, as well as with episodes of mastitis in lactating animals. This review describes the complex interrelationship between vitamin A, mastitis, and MTCT of HIV-1 via mothers' milk. Current gaps in knowledge, as well as recommendations for future research efforts, are also discussed.

Breastmilk RNA viral load in HIV-infected South African women: effects of subclinical mastitis and infant feeding.

OBJECTIVE: To investigate determinants of breastmilk RNA viral load among HIV-infected South African women, with particular attention to infant feeding mode and subclinical mastitis. DESIGN: Observational, longitudinal study. METHODS: Information on current infant feeding practice and a spot milk sample from each breast were obtained from 145 HIV-infected lactating women at 1, 6 and 14 weeks postpartum. The sodium/potassium (Na+/K+) ratio in milk was taken as an indicator of subclinical mastitis. The association between milk RNA viral load and maternal and infant characteristics was investigated using uni- and multivariate models. RESULTS: Milk viral load was below the limit of detection of the HIV RNA assay (< 200 copies/ml) in 63/185 (34.1%), 73/193 (37.8%) and 68/160 (42.5%) of samples at 1, 6 and 14 weeks, respectively. Multivariate models predicted between 13 and 26% of variability in milk viral load in the first 14 weeks. Low blood CD4 cell count (< 200 x 10(6) cells/l) during pregnancy and raised milk Na+/K+ ratio were significantly associated with raised milk RNA viral load at all times, but there were no consistent associations between infant feeding mode and RNA viral load in milk. There was a non-significant trend for the six infants known to be infected postnatally, compared with the 88 infants who remained uninfected, to have been exposed to breastmilk of higher viral load at each time point. CONCLUSIONS: Breast milk HIV RNA viral load in the first 14 weeks of life varied; high levels were associated with subclinical mastitis and severe maternal immunosuppression. Multivariate models had limited predictive value for milk RNA viral load, illustrating the multiple contributors to viral load.

Mastitis and transmission of human immunodeficiency virus through breast milk.

Mastitis, an inflammation in the breast, has recently been linked with higher human immunodeficiency virus (HIV) load in breast milk and higher risk of mother-to-child transmission of HIV. Among 334 HIV-infected women in Malawi who were breastfeeding, the prevalence of mastitis, as indicated by elevated breast milk sodium, was 16.4% at six weeks and 2.8% at six months postpartum. Mastitis is associated with significantly higher concentrations of immunological and inflammatory mediators in breast milk, including lactoferrin, lysozyme, secretory leukocyte protease inhibitor, interleukin-8, and RANTES. Mastitis is potentially preventable by improving micronutrient status of breastfeeding women and can be treated with antibiotics and clinical management. These studies in Malawi suggest that mastitis may contribute to transmission of HIV through breast milk.

Experimental Maedi Visna Virus Infection in sheep: a morphological, immunohistochemical and PCR study after three years of infection.

A morphological, immunohistochemical and polymerase chain reaction (PCR) study was performed on eight ewes experimentally infected with an Italian strain of Maedi-Visna Virus (MVV) in order to evaluate the lesions and the viral distribution after three years of infection. At the moment of euthanasia, seven sheep were seropositive for MVV, while one sheep in poor body conditions was seronegative since one year. Lungs, pulmonary lymph nodes, udder, supramammary lymph nodes, carpal joints, the CNS, spleen and bone marrow of the eight infected sheep were collected for histology, for immunohistochemical detection of the MVV core protein p28 and for PCR amplification of a 218 bp viral DNA sequence of the pol region. The most common histological findings consisted of interstitial lymphoproliferative pneumonia and lymphoproliferative mastitis of different severity, while no lesions were observed in the CNS. MVV p28 antigen was immunohistochemically labelled in lungs, udder, pulmonary lymph nodes, spleen and bone marrow but not in the CNS of all the eight infected sheep. A 218 bp sequence of MVV pol region was detected in lung of a seropositive and of the seroconverted negative sheep. The results suggest that (i) MVV causes heterogeneous lesions in homogeneously reared ewes, (ii) MVV p28 antigen is detectable not only in inflammed target organs, but also in pulmonary lymph nodes, spleen and bone marrow, and (iii) immunohistochemistry and PCR are useful methods for Maedi-Visna diagnosis in suspected cases, also when serological tests are negative.

The carriage of Pasteurella haemolytica in sheep and its transfer between ewes and lambs in relation to mastitis.

The possible presence of Pasteurella haemolytica in the mouth of lambs and on the skin of the teats of ewes was investigated. The organism was found in the mouth of ewes and lambs and, soon after lambing, on the teat skin of ewes. It was not isolated from the teat skin of pregnant ewes 1-14 days before lambing or from the teat skin one week after the lambs had been weaned. The transfer of P. haemolytica to the teat skin is undoubtedly mediated by the lamb. There is ample opportunity for the teat orifice to be exposed to P. haemolytica during the suckling period and it is known that only a few colony-forming units of virulent organisms are required to initiate mastitis.

The effect of a natural maedi-visna virus infection on the productivity of South African sheep.

A cohort study was conducted in order to measure the effect of the chronic indurative lymphocytic mastitis caused by the South African strain of maedi visna virus (MVV) on the pre-weaning growth of lambs born either of naturally infected or uninfected ewes kept under similar conditions. Fifty naturally infected ewes as well as another 40 from a maedi-visna-free source to be used as control animals, were purchased and kept in separate flocks which were managed in a similar way. All the ewes were of the same breed and 3-4 years old. During the adaptation period, and through the mating, pregnancy and lactation periods they were periodically monitored for the presence of MVV serum antibodies. The lambs were weighed at birth and thereafter every 2 weeks until the age of 90 days, when they were weaned. The ewes were then slaughtered, and their udders examined histologically and the number of lymphocytic follicles were counted and assessed. Although the calculated values indicated a correlation between the number of follicles in the udder and the reduction in the growth rate of the lambs, this was not statistically significant. Similarly, despite higher counts of lymphoid follicles in the udders of sero-positive ewes as compared to those that were sero-negative and the lower ewe productivity indexes in infected ewes, no statistically significant differences were found in the indexes of ewes in different follicle categories.

Dynamics of breast milk HIV-1 RNA with unilateral mastitis or abscess.

BACKGROUND: Mastitis and abscess in HIV-infected women increase the risk of breastfeeding transmission of HIV. Guidelines encourage women to stop breastfeeding on the affected breast and feed on the contralateral breast. However, impact of breast pathology on breast milk HIV dynamics is unknown. METHODS: HIV RNA was quantified in 211 breast milk samples collected before, during, and after a clinical mastitis or an abscess diagnosis from 38 HIV-infected women participating in a Zambian breastfeeding study. HIV RNA quantity was compared between affected and unaffected breasts over time using generalized estimating equation models. A sample of 115 women without breast pathology was selected as a control group. RESULTS: In the affected breast, breast milk HIV RNA quantity increased from the pre- to during-pathology period by log(10) 0.45 copies per milliliter [95% confidence interval (CI): 0.16 to 0.74], and after symptom resolution, HIV RNA levels were no different from prepathology levels (log10 -0.04 copies per milliliter 95% CI: -0.33 to 0.25). In the contralateral, unaffected breast, HIV RNA quantity did not significantly increase (log(10) 0.15 copies per milliliter, 95% CI: -0.41 to 0.10). Increase was more marked in women with abscess or with a greater number of mastitis symptoms. HIV RNA was not significantly different between affected and unaffected women, except at the time of diagnosis. CONCLUSIONS: Breast milk HIV RNA increased modestly in the affected breast with unilateral mastitis or abscess and returned to prepathology levels with symptom resolution. Contralateral HIV RNA was not affected. Results support guidelines encouraging feeding from the contralateral breast to minimize the risk of HIV transmission associated with unilateral breast pathology.

A polytropic caprine arthritis encephalitis virus promoter isolated from multiple tissues from a sheep with multisystemic lentivirus-associated inflammatory disease.

Caprine arthritis encephalitis virus (CAEV) is a lentivirus that infects both goats and sheep and is closely related to maedi-visna virus that infects sheep; collectively, these viruses are known as small ruminant lentiviruses (SRLV). Infection of goats and sheep with SRLV typically results in discrete inflammatory diseases which include arthritis, mastitis, pneumonia or encephalomyelitis. SRLV-infected animals concurrently demonstrating lentivirus-associated lesions in tissues of lung, mammary gland, joint synovium and the central nervous system are either very rare or have not been reported. Here we describe a novel CAEV promoter isolated from a sheep with multisystemic lentivirus-associated inflammatory disease including interstitial pneumonia, mastitis, polyarthritis and leukomyelitis. A single, novel SRLV promoter was cloned and sequenced from five different anatomical locations (brain stem, spinal cord, lung, mammary gland and carpal joint synovium), all of which demonstrated lesions characteristic of lentivirus associated inflammation. This SRLV promoter isolate was found to be closely related to CAEV promoters isolated from goats in northern California and other parts of the world. The promoter was denoted CAEV-ovine-MS (multisystemic disease); the stability of the transcription factor binding sites within the U3 promoter sequence are discussed.

Cytomegalovirus and Epstein-Barr virus in breast milk are associated with HIV-1 shedding but not with mastitis.

BACKGROUND: Breast milk HIV-1 load is associated with clinical and subclinical mastitis, and both milk viral load and mastitis are associated with increased mother-to-child-transmission of HIV-1 through breastfeeding. Bacterial infections may cause clinical mastitis, but whether other copathogens common in HIV-1 infection are associated with subclinical mastitis or HIV-1 shedding is unknown. DESIGN: A cross-sectional study of HIV-1-infected breastfeeding women in Zimbabwe was performed to examine the relationship between a wide range of breast coinfections, mastitis, and HIV-1 shedding. METHODS: Breast milk was cultured for bacteria and fungi and tested by PCR for mycobacteria, mycoplasmas, human herpesvirus (HHV)-6, HHV-7, HHV-8, cytomegalovirus, Epstein-Barr virus, and HIV-1 RNA and DNA. Symptoms of clinical mastitis were documented and subclinical mastitis was identified by breast milk sodium concentration (Na) and leukocyte counts. RESULTS: Coinfections of milk were not associated with clinical or subclinical mastitis in the 217 women studied. Detection of HIV-1 RNA, but not DNA, in breast milk was associated with cytomegalovirus concentration (odds ratio = 1.8, P = 0.002) and detection of Epstein-Barr virus (odds ratio = 3.8, P = 0.0003) but not other coinfections in multivariate analysis. CONCLUSION: Coinfection of breast milk with bacteria, fungi, or herpes viruses was not associated with mastitis. The associations between shedding of cytomegalovirus and Epstein-Barr virus with HIV-1 in milk suggest a local interaction between herpes virus infection and HIV-1 independent of mastitis. Cytomegalovirus and Epstein-Barr virus infections may impact HIV-1 shedding in breast milk and the risk of MTCT.

Veterinary field test as screening tool for mastitis and HIV-1 viral load in breastmilk from HIV-infected Zambian women.

Clinical and subclinical mastitis increase the risk of mother-to-child transmission (MTCT) of HIV-1 through breastfeeding. We hypothesized that a field test for mastitis used for bovine milk, the California Mastitis Test, would detect high cell counts in milk of HIV-infected women. We also investigated whether total milk cell count would positively correlate with viral HIV-1 RNA in the milk of 128 HIV-positive Zambian women. Mean cell counts in each California Mastitis Test scoring category were significantly different (p < 0.01, n = 232). In a subset of 4-month postpartum milk samples tested for HIV-1 RNA, viral RNA levels did not significantly correlate with total cell count (r = 0.166, p = .244). The CMT may serve as a screening tool for mastitis in breastmilk, but total cell count does not correlate with HIV-1 RNA levels. Since both cell-free and cell-associated virus are associated with increased risk of MTCT, investigation of the relationship between total milk cell count and HIV-1 proviral DNA is warranted before a conclusive determination is made regarding use of the CMT as a clinical screening tool to detect cases at high risk for breastmilk transmission.

Laboratory indicators of mastitis are not associated with elevated HIV-1 DNA loads or predictive of HIV-1 RNA loads in breast milk.

BACKGROUND: Mother-to-child transmission (MTCT) of HIV-1 has been associated with symptomatic and asymptomatic mastitis and with the quantity of HIV-1 RNA and DNA in maternal milk. An improved understanding of the relationship between indicators of inflammation and HIV-1 loads in breast milk could improve MTCT prevention strategies. METHODS: In a cross-sectional study, laboratory indicators of mastitis (breast milk sodium [Na(+)] concentration, sodium : potassium ratio [Na(+) : K(+)], and leukocyte count) were related to breast milk HIV-1 RNA and DNA loads and were evaluated for predicting viral loads in milk. RESULTS: Mastitis was present in 63 (15%) of 407, 60 (15%) of 407, and 76 (18%) of 412 milk specimens, as defined by Na(+) concentration >12 mmol/L, Na(+) : K(+) >1, and total leukocyte counts > or =10(6) cells/mL, respectively. Each indicator was associated with an increased milk HIV-1 RNA load (P<.05) but not with HIV-1 DNA load. Neutrophils correlated better with milk HIV-1 RNA load than total leukocytes. However, neither neutrophil count, Na(+) concentration, nor Na(+) : K(+) displayed a threshold that was both sensitive and specific for the detection of HIV-1 RNA in milk at thresholds of > or =50 or > or =10(4) copies/mL. CONCLUSIONS: HIV-1 DNA loads in breast milk were not increased during mastitis. Neither milk cell counts nor electrolyte concentrations were useful predictors of milk HIV-1 RNA or DNA loads for individual women.