Antenatal syphilis screening using point-of-care testing in Sub-Saharan African countries: a cost-effectiveness analysis.

BACKGROUND: Untreated syphilis in pregnancy is associated with adverse clinical outcomes for the infant. Most syphilis infections occur in sub-Saharan Africa (SSA), where coverage of antenatal screening for syphilis is inadequate. Recently introduced point-of-care syphilis tests have high accuracy and demonstrate potential to increase coverage of antenatal screening. However, country-specific cost-effectiveness data for these tests are limited. The objective of this analysis was to evaluate the cost-effectiveness and budget impact of antenatal syphilis screening for 43 countries in SSA and estimate the impact of universal screening on stillbirths, neonatal deaths, congenital syphilis, and disability-adjusted life years (DALYs) averted. METHODS AND FINDINGS: The decision analytic model reflected the perspective of the national health care system and was based on the sensitivity (86%) and specificity (99%) reported for the immunochromatographic strip (ICS) test. Clinical outcomes of infants born to syphilis-infected mothers on the end points of stillbirth, neonatal death, and congenital syphilis were obtained from published sources. Treatment was assumed to consist of three injections of benzathine penicillin. Country-specific inputs included the antenatal prevalence of syphilis, annual number of live births, proportion of women with at least one antenatal care visit, per capita gross national income, and estimated hourly nurse wages. In all 43 sub-Saharan African countries analyzed, syphilis screening is highly cost-effective, with an average cost/DALY averted of US$11 (range: US$2-US$48). Screening remains highly cost-effective even if the average prevalence falls from the current rate of 3.1% (range: 0.6%-14.0%) to 0.038% (range: 0.002%-0.113%). Universal antenatal screening of pregnant women in clinics may reduce the annual number of stillbirths by up to 64,000, neonatal deaths by up to 25,000, and annual incidence of congenital syphilis by up to 32,000, and avert up to 2.6 million DALYs at an estimated annual direct medical cost of US$20.8 million. CONCLUSIONS: Use of ICS tests for antenatal syphilis screening is highly cost-effective in SSA. Substantial reduction in DALYs can be achieved at a relatively modest budget impact. In SSA, antenatal programs should expand access to syphilis screening using the ICS test. Please see later in the article for the Editors' Summary.

Fetal bacterial infections in antepartum stillbirth: a case series.

OBJECTIVES: This study aims to assess the frequency of fetal bacterial infections in stillbirth (SB) and to evaluate the best samples for the diagnosis of infection-related SB. STUDY DESIGN: Consecutive cases of antepartum SB were enrolled. Vaginal and placental swabs, as well as heart blood cultures and surface swabs from the neonate, were collected. Histological examinations were performed by the same examiner. Immunohistochemistry for leukocyte common antigen was performed in the placenta and fetus. Each case was discussed in a multidisciplinary audit. RESULTS: One hundred and nine cases were enrolled. Fetal blood cultures were positive in 20/95 cases (21%). Significant histological findings in the placenta/cord and in at least one fetal organ were observed in 8 cases of them (4 Group B Streptococcus GBS, 2 Listeria monocytogenes, 1 Coagulase negative Staphylococcus, 1 Pseudomonas aeruginosa). Neither tissue damage nor inflammatory infiltrate was found in the 12 remnant cases. Funisitis while not histological chorioamnionitis was associated with microbiological findings. Positive findings in maternal/placental/fetal swabs occurred in 18-32% of cases with both negative fetal blood cultures and histopathological findings. With the exception of GBS, no other bacteria agent could be detected by any of the swabs. CONCLUSIONS: Eight cases (8.4%) fulfilled both microbiological and histology criteria allowing the diagnosis of SB-related fetal infection demonstrating that search for infections is essential in SB evaluation. Fetal blood culture, placenta swab for GBS and search for histological funisitis are mandatory actions within the SB work-up in order to guide pathology examination and reach clinical conclusions.

An Arthrobacter spp. bacteremia leading to fetal death and maternal disseminated intravascular coagulation.

A 34-year-old parous woman developed high fever and threatened preterm labor after a 1-day trip, for which she was receiving prenatal care at a hospital. Three days after onset, at 24 4/7 weeks of gestation, she was transferred to our hospital in an emergency. Soon after the woman's arrival at our hospital, the infant was spontaneously stillborn via a transvaginal delivery. Laboratory tests revealed severe maternal disseminated intravascular coagulation with renal and liver insufficiency. Histopathologic examination of the placenta revealed vast fibrin deposition and remarkable neutrophilic infiltration in the intervillous space, suggesting a rare bacterial infection caused by Arthrobacter spp. The bacteria were predominantly detected in the placenta and maternal blood serum by common bacterial 16S rRNA sequencing after polymerase chain reaction amplification. We report the first case, to our knowledge, of bacteremia with Arthrobacter spp., which may lead to maternal disseminated intravascular coagulation and intrauterine fetal death.

Anthrax cases in pregnant and postpartum women: a systematic review.

OBJECTIVE: To describe the worldwide experience of Bacillus anthracis infection reported in pregnant, postpartum, and lactating women. DATA SOURCES: Studies were identified through MEDLINE, Web of Science, Embase, and Global Health databases from inception until May 2012. The key words (["anthrax" or "anthracis"] and ["pregna*" or "matern*" or "postpartum" or "puerperal" or "lact*" or "breastfed*" or "breastfeed*" or "fetal" or "fetus" or "neonate" or "newborn" or "abort*" or "uterus"]) were used. Additionally, all references from selected articles were reviewed, hand searches were conducted, and relevant authors were contacted. METHODS OF STUDY SELECTION: The inclusion criteria were: published articles referring to women diagnosed with an infection due to exposure to B anthracis during pregnancy, the postpartum period, or during lactation; any article type reporting patient-specific data; articles in any language; and nonduplicate cases. Non-English articles were professionally translated. Duplicate reports, unpublished reports, and review articles depicting previously identified cases were excluded. TABULATION, INTEGRATION, AND RESULTS: Two authors independently reviewed articles for inclusion. The primary search of the four databases yielded 1,340 articles, and the secondary crossreference search revealed 146 articles. Fourteen articles met the inclusion criteria. In total, 20 cases of B anthracis infection were found, 17 in pregnant women, two in postpartum women, and one case in a lactating woman. Among these reports, 16 women died and 12 fetal or neonatal losses were reported. Of these fatal cases, most predated the advent of antibiotics. CONCLUSIONS: Based on these case reports, B anthracis infection in pregnant and postpartum women is associated with high rates of maternal and fetal death. Evidence of possible maternal-fetal transmission of B anthracis infection was identified in early case reports.

Meningoencephalitis due to Listeria monocytogenes in a pregnant rhesus macaque (Macaca mulatta).

We here report a spontaneous case of meningoencephalitis due to Listeria monocytogenes in an adult primiparous rhesus macaque (Macaca mulatta) during an outbreak of listeriosis in an outdoor enclosure. Clinical signs included tremors, abnormal posture, and altered mental status. Hematology and analyses of cerebrospinal fluid were consistent with bacterial infection. Pure cultures of L. monocytogenes were recovered from the placenta-abortus, cerebrospinal fluid, and brain tissue. The macaque did not respond to treatment and was euthanized. Histopathologic examination of the brain revealed acute meningoencephalitis. This case represents an unusual clinical and pathologic presentation of listeriosis in a nonhuman primate in which the dam and fetus both were affected.

[Pregnancies complicated by maternal syphilis and fetal death]. / Gestações complicadas por sífilis materna e óbito fetal.

PURPOSE: To describe the characteristics of pregnancies complicated by maternal syphilis and fetal death. METHODS: Retrospective descriptive study performed by reviewing the medical records of 48 pregnant women with maternal syphilis and fetal death outcome admitted to Hospital Geral de Nova Iguaçu, Baixada Fluminense, State of Rio de Janeiro, during the period from 2005 to 2008. Birth weight >500 g and fetal death documented by Death Certificate were the inclusion criteria. The following aspects were analyzed: sociodemographic factors, reproductive history, aspects of the current pregnancy, prenatal care, Venereal Disease Research Laboratory (VDRL) testing, and other gestational conditions, in addition to syphilis. The fetal deaths were classified as maternal, placental or fetal. Percentage, mean, standard deviation (SD), maximum and minimum values were reported. RESULTS: The mean maternal age was 22.7 years (SD=0.9 years), and at least 50% of the patients had low educational level. At hospital admission, 68.8% of the subjects were in the third trimester, with a mean gestational age of 29.2 weeks (SD=0.5), and more than 50% were in labor. The vast majority of fetal deaths (93%) occurred before maternal hospitalization. Among the patients who received prenatal care (54.2%), 30.8% had no VDRL test, 30.8 and 15.4% had a reactive and non-reactive result, respectively, and none had more than one prenatal VDRL test. At the time of childbirth, most of the mothers (95.8%) carried out VDRL testing. Overall, the VDRL titers varied from 1:1 to 1:512, with predominant values >1:4 (91.7%). In 23% of cases other clinical conditions related to fetal death, in addition to syphilis, were found. CONCLUSIONS: The infection was the main clinically identified cause of fetal death in this patient series. Fetal death occurred during the preterm period and in the presence of high titers of maternal infection, suggesting recent syphilis infection.

Gestações complicadas por sífilis materna e óbito fetal / Pregnancies complicated by maternal syphilis and fetal death

OBJETIVO: Descrever as características de gestações complicadas por sífilis materna e óbito fetal. MÉTODOS: Foi feito um estudo retrospectivo descritivo conduzido por revisão de prontuários de 48 gestantes com sífilis materna e desfecho de óbito fetal, admitidas no período 2005-2008, no Hospital Geral de Nova Iguaçu, Baixada Fluminense, Estado do Rio de Janeiro. O peso ao nascer >500 g e o óbito fetal documentado por declaração de óbito foram os critérios de inclusão. Os seguintes aspectos foram analisados: sociodemográficos, antecedentes reprodutivos, aspectos da gestação atual, cuidados de pré-natal, realização e resultados do teste Venereal Disease Research Laboratory (VDRL), presença de intercorrências na gestação, além da sífilis, sendo as mortes fetais classificadas como materna, placentária ou fetal. Os resultados foram apresentados por porcentagem, média, desvio padrão (DP) e valor máximo e mínimo. RESULTADOS: A média de idade materna foi de 22,7 anos (DP=0,9 anos) e pelo menos metade das pacientes tinham baixo grau de escolaridade. Na admissão hospitalar, 68,8 por cento do grupo se encontrava no terceiro trimestre e com média de idade gestacional de 29,2 semanas (DP=0,5); mais de 50 por cento estava em trabalho de parto. A grande maioria dos casos de óbito fetal (93 por cento) ocorreu antes da hospitalização materna. Entre as pacientes que frequentaram o pré-natal (54,2 por cento), 30,8 por cento não realizaram o VDRL, 30,8 e 15,4 por cento tiveram resultado reativo e não-reativo, respectivamente e nenhuma teve mais de um VDRL no pré-natal. No momento do parto, a maioria das pacientes (95,8 por cento) realizou o VDRL. No geral, a titulação do VDRL variou de 1:1 a 1:512, predominando titulações >1:4 (91,7 por cento). Em 23 por cento dos casos foram encontradas outras condições relacionadas ao óbito fetal, além da sífilis. CONCLUSÕES: A infecção foi a principal causa clinicamente identificada do decesso fetal nesta série de casos. O desfecho de feto morto ocorreu no pré-termo e na presença de títulos altos de infecção materna, sugestivos de sífilis recente.

PURPOSE: To describe the characteristics of pregnancies complicated by maternal syphilis and fetal death. METHODS: Retrospective descriptive study performed by reviewing the medical records of 48 pregnant women with maternal syphilis and fetal death outcome admitted to Hospital Geral de Nova Iguaçu, Baixada Fluminense, State of Rio de Janeiro, during the period from 2005 to 2008. Birth weight >500 g and fetal death documented by Death Certificate were the inclusion criteria. The following aspects were analyzed: sociodemographic factors, reproductive history, aspects of the current pregnancy, prenatal care, Venereal Disease Research Laboratory (VDRL) testing, and other gestational conditions, in addition to syphilis. The fetal deaths were classified as maternal, placental or fetal. Percentage, mean, standard deviation (SD), maximum and minimum values were reported. RESULTS: The mean maternal age was 22.7 years (SD=0.9 years), and at least 50 percent of the patients had low educational level. At hospital admission, 68.8 percent of the subjects were in the third trimester, with a mean gestational age of 29.2 weeks (SD=0.5), and more than 50 percent were in labor. The vast majority of fetal deaths (93 percent) occurred before maternal hospitalization. Among the patients who received prenatal care (54.2 percent), 30.8 percent had no VDRL test, 30.8 and 15.4 percent had a reactive and non-reactive result, respectively, and none had more than one prenatal VDRL test. At the time of childbirth, most of the mothers (95.8 percent) carried out VDRL testing. Overall, the VDRL titers varied from 1:1 to 1:512, with predominant values >1:4 (91.7 percent). In 23 percent of cases other clinical conditions related to fetal death, in addition to syphilis, were found. CONCLUSIONS: The infection was the main clinically identified cause of fetal death in this patient series. Fetal death occurred during the preterm period and in the presence of high titers of maternal infection, suggesting recent syphilis infection.

Prevalence of Coxiella burnetii infections in aborted fetuses and stillborn calves.

Coxiella burnetii infections are mostly subclinical in cattle, but can occasionally be associated with abortion. In the present study, 100 aborted fetuses or stillborn calves that were submitted for postmortem examination between September 2007 and March 2008 were examined for infection with C burnetii. Samples of both pooled fetal tissues and placental cotyledon were tested using a real-time PCR assay. In addition, the sections of placental cotyledon were examined using immunohistochemistry (IHC). The IHC of four placentas was positive. The PCR results of the IHC-positive placentas were high positive (HP); the PCR results of the organs of these four fetuses and calves varied from low positive (LP) to HP. The four IHC-positive fetuses had a gestation length of seven to nine months. All four placentas had histological signs of inflammation, but only one of four placentas had gross pathological signs of inflammation possibly due to a concomitant infection with Bacillus licheniformis. Five other IHC-negative placentas had (high) positive PCR results; the PCR results of the organs of these fetuses were LP or negative. The present study indicates that C burnetii infections are detected in a limited percentage of aborted fetuses and stillborn calves by IHC. To assess the importance of placentas with PCR-positive and IHC-negative test results, more research is needed.

Intrauterine fetal demise due to streptococcal toxic shock syndrome: a case report.

BACKGROUND: Toxic shock syndrome caused by group A streptococci (GAS) is rare around the time of delivery, but it may predispose pregnant women to a life-threatening condition. CASE: A 32-year-old primigravida at 21 weeks of gestation was taken to our hospital with acute severe abdominal pain following fever. On admission the fetus was found to be dead, and intrauterine fetal demise due to placental abruption was suspected. An emergency cesarean section found no sign of placental abruption. Soon after the surgery, the patient went into shock but was successfully treated with intensive care. Although repeated blood cultures failed to detect microorganisms, the patient was positive for streptococcal pyrogenic toxin A, which is a superantigen of GAS. CONCLUSION: Once GAS infection is suspected, regardless of negative blood cultures, supportive care in the intensive care unit is mandatory.

Placental intravascular organisms: a case report.

Ascending amniotic fluid bacterial infection is a cause of perinatal morbidity and mortality. A diagnosis of amniotic cavity infection can be inferred by documenting maternal (acute chorioamnionitis) and/or fetal (chorionic plate vasculitis; umbilical vasculitis/funisitis) inflammatory response. A definitive diagnosis of intrauterine/neonatal sepsis as a cause of stillbirth requires positive blood cultures obtained at postmortem examination. However, if postmortem examination is not performed, acute chorioamnionitis with/without fetal inflammatory response cannot be classified as a cause of demise. We present a case of intrauterine demise associated with acute chorioamnionitis, villitis, and intervillositis of the placenta. Although postmortem examination was denied, a conclusive diagnosis of intrauterine sepsis could be rendered by demonstration of gram-positive cocci within fetal vessels of umbilical cord, chorionic plate, and stem villi. This report highlights the importance of identification of placental intravascular organisms as unequivocal evidence of fetal sepsis, especially in cases where cultures cannot be obtained.

Identifying unreported and undiagnosed cases of congenital syphilis in Arizona using live birth and fetal death registries.

To investigate the drop in reported congenital syphilis cases from 28 in 2005 to 16 in 2006, the Arizona infant registries were cross matched with reported syphilis test among women in th estat STD database. Six previously unreported cases were identified; four live births and two still births.

Chorioamnionitis and intrauterine fetal death after second-trimester amniocentesis.

We report an intrauterine fetal death that occurred less than 24 h after transabdominal amniocentesis. Chorioamnionitis was confirmed by amniotic fluid culture which showed multiple enteric organisms and postmortem examination of the fetus that showed Clostridium perfringens. The patient was treated with intravenous broad-spectrum antibiotics and uterine evacuation and her condition rapidly improved. Intra-amniotic infection after amniocentesis requires a high index of suspicion and prompt aggressive treatment with broad spectrum antibiotics and uterine evacuation to prevent maternal sepsis-related morbidity and mortality.

[Syphilis as cause of foetal death]. / Syfilis som årsag til dødfødsel.

Syphilis is a well-known cause of foetal death. We describe a Danish case of foetal death in week 31 + 0 in an Iraqi-born woman. The foetus had ascites. Blood samples were positive for IgG and IgM, for syphilis, and immunohistochemical staining of the placenta showed Treponema pallidum in relation to the vessels of the umbilical cord. Congenital syphilis should be kept in mind even though it is rare in Denmark.

Infection and stillbirth.

Infection may cause stillbirth by several mechanisms, including direct infection, placental damage, and severe maternal illness. Various organisms have been associated with stillbirth, including many bacteria, viruses, and protozoa. In developed countries, between 10% and 25% of stillbirths may be caused by an infection, whereas in developing countries, which have much higher stillbirth rates, the contribution of infection is much greater. In developed countries, ascending bacterial infection, both before and after membrane rupture, with organisms such as Escherichia coli, group B streptococci, and Ureaplasma urealyticum is usually the most common infectious cause of stillbirth. However, in areas where syphilis is prevalent, up to half of all stillbirths may be caused by this infection alone. Malaria may be an important cause of stillbirth in women infected for the first time in pregnancy. The two most important viral causes of stillbirth are parvovirus and Coxsackie virus, although a number of other viral infections appear to be causal. Toxoplasma gondii, Listeria monocytogenes, and the organisms that cause leptospirosis, Q fever, and Lyme disease have all been implicated as etiologic for stillbirth. In certain developing countries, the stillbirth rate is high and the infection-related component so great that achieving a substantial reduction in stillbirth should be possible by reducing maternal infections. However, because infection-related stillbirth is uncommon in developed countries, and because those that do occur are caused by a wide variety of organisms, reducing this etiologic component of stillbirth much further will be difficult.

A novel Brucella isolate in association with two cases of stillbirth in non-human primates - first report.

BACKGROUND: Brucellosis is veterinary and human health problem. METHODS: A 13-year-old wild caught multiparous and an 8-year-old colony-born nulliparous baboon had stillbirths in the second trimester of pregnancy. Culture isolates from both postpartum uteruses were characterized using traditional biochemical analysis, PCR, and multilocus sequencing. RESULTS: The isolates morphologically resembled Brucella although their phenotypic characteristics were not consistent with any currently described species. The isolates represent a novel lineage within the genus with unique alleles, not previously seen in surveys of greater than 300 isolates representing the known diversity of the genus, present at 5/9 loci examined. CONCLUSIONS: The described cases are to the best of our knowledge the first presentation of a naturally acquired Brucella infection in non-human primates associated with stillbirths from the same colony where Brucella seropositivity in the baboons was described 45 years ago. The organism appears to represent a previously undescribed Brucella species.

[Listeria monocytogenes infection in pregnancy: experience of Pontificia Universidad Católica de Chile University Hospital]. / Infecciones por Listeria monocytogenes en mujeres embarazadas: experiencia del Hospital Clínico de la Pontificia Universidad Católica de Chile.

Listeria monocytogenes is Gram-positive facultative intracellular pathogen often foodborne and found elsewhere. It is an uncommon cause of illness in the general population. However, it is an important cause of severe infection in neonates, pregnant women, elderly and immunosuppressed patients. Listeriosis has unique preference for pregnant women. Maternal listeriosis is a diagnostic challenge, and intrauterine infection can lead to severe complications such as amnionitis, preterm labor, spontaneous abortion, stillbirth and neonatal sepsis. From 2001 to 2005, 16 patients with L. monocytogenes were identified in this hospital; four (25%) were pregnant women. Clinical and laboratory findings are described. There were 3 preterm deliveries and 1 spontaneous second trimester abortion. Three women with listeriosis had no predisposing factors other than pregnancy. One patient was on immunosupressive drugs for ulcerative colitis. Fever was the most common symptom. Infected neonates were most commonly diagnosed with early-onset listeriosis (two cases) or fetal demise (one case). Pregnancy can be the only risk factor for listeriosis. Listeriosis should be considered during the evaluation of febrile syndrome in pregnancy as this condition can be the only risk factor. Blood and amniotic fluid cultures are useful diagnostic tests. Perinatal complications remains high.

Infecciones por Listeria monocytogenes en mujeres embarazadas: experiencia del Hospital Clínico de la Pontificia Universidad Católica de Chile / Listeria monocytogenes infection in pregnaney: experience of Pontificia Universidad Católica de Chile University Hospital

Listeria monocytogenes is Gram-positive facultative intracellular pathogen often foodborne and found elsewhere. It is an uncommon cause of illness in the general population. However, it is an important cause of severe infection in neonates, pregnant women, elderly and immunosuppressed patients. Listeriosis has unique preference for pregnant women. Maternal listeriosis is a diagnostic challenge, and intrauterine infection can lead to severe complications such as amnionitis, preterm labor, spontaneous abortion, stillbirth and neonatal sepsis. From 2001 to 2005, 16 patients with L. monocytogenes were identified in this hospital; four (25 percent) were pregnant women. Clinical and laboratory findings are described. There were 3 preterm deliveries and 1 spontaneous second trimester abortion. Three women with listeriosis had no predisposing factors other than pregnaney. One patient was on immunosupressive drugs for ulcerative colitis. Fever was the most common symptom. Infected neonates were most commonly diagnosed with early-onset listeriosis (two cases) or fetal demise (one case). Pregnaney can be the only risk factor for listeriosis. Listeriosis should be considered during the evaluation of febrile syndrome in pregnaney as this condition can be the only risk factor. Blood and amniotic fluid cultures are useful diagnostic tests. Perinatal complications remains high.

Listeria monocytogenes es un bacilo grampositivo, intracelular facultativo, que se encuentra ampliamente difundido en la naturaleza, frecuentemente en alimentos. Las infecciones afectan principalmente a pacientes inmunocomprometidos, ancianos, mujeres embarazadas y neonatos. La infección intrauterina puede producir importantes complicaciones como corioamnionitis, parto de pre-término, aborto espontáneo de primer o segundo trimestre, mortinatos y sepsis neonatal. En el período 2001-2005, 16 pacientes con infección por L. monocytogenes fueron identificados en nuestro hospital. Cuatro de ellos (25 por ciento) se presentaron en mujeres embarazadas; se describen sus características clínicas y de laboratorio. Hubo tres partos de pre-término y un aborto espontáneo de segundo trimestre. En tres de las cuatro pacientes, el único factor de riesgo fue el embarazo. Una paciente recibía terapia inmunosupresora por una colitis ulcerosa. Fiebre fue el síntoma más frecuente. El compromiso feto-neonatal se manifestó por listeriosis neonatal precoz (dos casos) y mortinato (un caso). El embarazo puede ser el único factor predisponente a desarrollar listeriosis. Ésta debe considerarse en la evaluación del síndrome febril de una mujer embarazada. Los cultivos de sangre y líquido amniótico son útiles para su diagnóstico. La tasa de complicaciones perinatales permanece elevada.