(BQ) Part 2 book “Neurology and pregnancy - Clinical management” has contents: Infections in pregnancy, idiopathic intracranial hypertension, vascular malformations of the brain in pregnancy, pituitary disease in pregnancy, neuro-oncology in pregnancy, multiple sclerosis and pregnancy, nutritional deficiencies in pregnancy,… and other contents.
14 Infections in pregnancy Iskandar Azwa, Michael S Marsh, and David A Hawkins INTRODUCTION Despite the advent of antibiotics and improved diagnostic facilities, infectious diseases in pregnancy continue to contribute significantly to maternal and neonatal morbidity and mortality (1) These are most common in the developing world About 99% of maternal deaths in the world in 2005 occurred in developing countries and 25% of maternal deaths in the developing world are due to infections in pregnancy mainly due to puerperal sepsis and septic abortion Obstetric sepsis was the leading cause of maternal mortality in the United Kingdom until the introduction of antibiotics into clinical practice in the late 1930s The incidence has now declined rapidly but there were still 18 direct deaths from genital tract sepsis (0.06% of maternal deaths) reported in the 2003 to 2005 triennium in the Confidential Enquiry into Maternal Deaths (CEMD), the majority associated with beta-haemolytic streptococcus Lancefield group A and Escherichia coli infection (2) Eight out of the 18 deaths occurred during labour or before delivery The CEMD identified risk factors for maternal sepsis which included diabetes, anaemia, history of pelvic infection, impaired immunity, history of group B streptococcal infection, amniocentesis and other invasive intrauterine procedures, cervical cerclage, prolonged spontaneous rupture of membranes, caesarean section and retained products of conception post-miscarriage or -delivery Obesity was also identified as a risk factor for infection and led to practical difficulties in managing care The CEMD highlighted the need to avoid complacency in maternal infection and made a number of key specific recommendations It emphasised the importance of increased awareness by health care professionals of symptoms and signs of sepsis and septic shock and the importance of regular frequent observations if pelvic sepsis was suspected It also stressed the importance of implementation of guidelines within individual maternity units for the management of genital tract sepsis Prompt treatment with high-dose broad-spectrum antibiotics should be started prior to obtaining microbiology results Maternal infections also have a major impact in the transmission of infections to the fetus, with a risk of adverse outcomes such as preterm deliveries, stillbirth, intrauterine growth restriction, congenital anomalies and neonatal infection In addition, increased foreign travel of pregnant women and the increase in immigrants from developing countries pose challenges to obstetricians and neonatologists in the overall management of infectious diseases in the United Kingdom Early involvement of a multidisciplinary team involving microbiologists, maternal-fetal medicine specialists, pharmacists and the critical care team is essential With evidence of sexually transmitted infections (STIs), genitourinary medicine specialists should be involved, and screening for other STIs should be undertaken In contrast to the common infections found in pregnancy, central nervous system (CNS) infections rarely compli- cate pregnancy, although when they the effects can be severe This chapter is divided into two sections The first discusses the screening and prevention of maternal infections and outlines some of the more common infections in pregnancy encountered in the developed world and their consequences Investigations and management to improve fetal and maternal outcomes are also discussed The second section deals with the CNS infections that can complicate pregnancy, including acute and chronic meningitis, encephalitis, brain abscess and spinal cord infection Management recommendations and guidelines have been based on the most recently revised guidelines from the U.K Royal College of Obstetricians and Gynaecologists (RCOG), Health Protection Agency (HPA), Department of Health (DOH), British Association for Sexual Health and HIV (BASHH), British HIV Association (BHIVA), U.S Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO), when available GENERAL INFECTION IN PREGNANCY The U.K Antenatal Screening Programme Since 2003, the U.K DOH has recommended screening all pregnant women with a single blood sample for human immunodeficiency virus (HIV), hepatitis B, rubella and syphilis during their first and all subsequent pregnancies (3) Other infections, not routinely investigated as part of the U.K antenatal screening programme, may be appropriate in other countries depending on the prevalence and risk of exposure These include cytomegalovirus (CMV), Chlamydia trachomatis, bacterial vaginosis, hepatitis C, group B streptococcus, toxoplasma, genital herpes simplex and human T-lymphotropic virus type-1 The important factors to consider when deciding to undertake screening of any infectious agent during pregnancy are the incidence of maternal infection, the risk of transmission to the fetus, the fetal damage if infection occurs, the availability of a reliable screening test and the availability of a safe and effective intervention to prevent fetal infection and reduce damage Prevention of Infection in Pregnant Women Pregnant women should be advised about preventive measures to reduce the risk of toxoplasma infection such as avoiding eating unwashed fruits, vegetables and inadequately cooked meat and avoiding contact with cat litter (4) To reduce the risk of listeriosis, pregnant women should avoid eating unpasteurised dairy products Pregnant women should also avoid unprotected intercourse if their partners are known to have HIV, hepatitis B, herpes simplex virus (HSV) or other STIs Women from non-endemic areas should be advised against travel to a malaria-endemic area (5) If travel is unavoidable, advice should be given about personal protection INFECTIONS IN PREGNANCY and chemoprophylaxis This advice also applies to previously immune women from malaria-endemic areas who have lived in the United Kingdom for more than years and who will therefore have lost much of their pre-existing immunity Protection against infection may be achieved by active and passive immunisation and all health care providers should obtain an immunisation history from women accessing prenatal care Live and/or live-attenuated vaccines are contraindicated in pregnancy due to theoretical concerns of teratogenicity If immunisation is to be given in anticipation of later risks, it is preferable for administration after the first trimester Immunisation programmes for rubella in childhood should provide protection throughout the childbearing years Following the mumps, measles and rubella (MMR) vaccine controversy, first reported in 1998, immunisation rates in the United Kingdom fell to 80% in 2003 However, the uptake of the vaccine is beginning to increase again, attaining 85% coverage in 2008 Women without a previous history of varicella should be screened for varicella zoster virus (VZV) antibodies at booking or rapidly after exposure, that is, within 48 hours after contact (5) Following exposure of a pregnant woman to varicella, non-immune women should be offered passive immunisation with varicella zoster immune globulin up to 10 days after contact Pregnant women are at increased risk of complications of influenza and all pregnant women should be offered the inactivated vaccine during the influenza season Women who are breastfeeding can still be immunised Immunology of Pregnancy The ‘paradox of pregnancy’, in which immunological tolerance to paternally derived fetal antigens is achieved despite an apparently adequate maternal defence against infection, continues to intrigue immunologists Evidence indicates that immunological tolerance of the fetus may occur by suppression of maternal cell-mediated immunity while retaining normal humoral (antibody-mediated) immunity This occurs as a result of decreased T-helper type 1(Th-1) lymphocyte responses (which stimulate cell-mediated immunity) with a shift to T-helper type (Th-2) dominance (which augment the humoral immune response) (6) The cell-mediated immunity is responsible for controlling intracellular pathogens and the immunological changes that occur in pregnancy may lead to increased severity and susceptibility to intracellular pathogens, including viruses, intracellular bacteria and parasites Effect of Infections on the Fetus Infections that affect the fetus and neonate are predominantly viral infections with a smaller number due to bacterial and protozoal infections Infections can develop in the neonate transplacentally, perinatally (from vaginal secretions or blood), or post-natally (from breast milk) Blood-borne viruses such as HIV, hepatitis B and C are mainly associated with perinatal infections, whereas rubella, CMV, parvovirus B19 and VZV are associated with in utero infection and placental transmission Infections traditionally known to produce congenital defects have been described with the acronym TORCH (toxoplasma, others, rubella, CMV, herpes) The ‘others’ category has now rapidly expanded to include parvovirus B19, VZV, West Nile virus, measles virus, enteroviruses, adenovirus and HIV The effect of infection in the fetus is determined by the virulence of microbes, the size of the inoculum, the immune response of the fetus at different gestational ages 135 and passively derived maternal antibodies Infection in pregnancy can lead to miscarriage, stillbirth, prematurity, structural defects and intrauterine growth restriction Investigation of Suspected Infection in Pregnancy Serological methods are often used for diagnosing viral infections in pregnancy and look for changes in immunoglobulin G (IgG) antibody titres with serial samples and the presence of immunoglobulin M (IgM) in order to determine if recent infection has occurred It is often helpful to compare a current sample with any previous samples taken earlier in the pregnancy, for example, samples taken at the time of booking, which are often stored in the laboratory for a period of time Absence of IgG antibodies in early pregnancy identifies susceptible women The presence of IgG antibodies suggests previous infection or vaccination Measurement of IgG avidity when available is useful Low IgG avidity indicates primary infection This is based on the fact that antibody binds less avidly to antigens during the early phases than in the later or chronic phase of infection In order to aid interpretation of serological tests, it is important to give as much clinical information as possible to the laboratory such as date and type of exposure, time of symptom onset, history of previous vaccination or infection and gestation of pregnancy It is important to remember that only some cases of maternal infection will result in fetal infection and not all cases of fetal infection will result in the fetus being affected or damaged by infection Referral to a fetal medicine unit for prenatal diagnostic testing such as amniotic fluid culture and polymerase chain reaction (PCR) may establish whether a fetus has been infected, but it cannot confirm or refute the possibility that the fetus has been affected Uterine Infections Chorioamnionitis Chorioamnionitis is infection or inflammation of the amniotic fluid and/or the fetal membranes, the chorion and amnion It can be either a histological or clinical diagnosis Clinical chorioamnionitis is present in up to 5% of term deliveries and in 10% to 25% of preterm deliveries, with the highest risk in those with preterm premature rupture of membranes (PPROM) (6) Other risk factors of chorioamnionitis include prolonged labour, repeated vaginal examinations, internal fetal monitoring, bacterial vaginosis and group B streptococcal colonisation Most cases are secondary to ascending infection from the vagina and cervix The diagnosis of chorioamnionitis is suggested by maternal fever, uterine tenderness, offensive liquor, maternal and fetal tachycardia Management involves expediting delivery and treatment with broad-spectrum intravenous antibiotics such as ampicillin, gentamicin and metronidazole (or clindamycin for anaerobic cover) after taking blood cultures Consequences of chorioamnionitis include premature rupture of membranes, premature labour, increased risk of neonatal pneumonia, bacteraemia and meningitis Severe chorioamnionitis may be accompanied by a fetal inflammatory response leading to vasculitis of the umbilical vessels and funisitis (inflammation of the umbilical cord’s connective tissue) There is a causal link between chorioamnionitis and brain injury in preterm and term infants It has been shown that there is a significant association between intrauterine infection and brain injury in the form of cerebral white matter lesions and periventricular leucomalacia in preterm neonates This association also applies to term infants, but with a much 136 NEUROLOGY AND PREGNANCY: CLINICAL MANAGEMENT stronger association It is uncertain whether the resulting brain injury is directly the result of maternal infection or indirectly via the fetus’ inflammatory response Puerperal Sepsis Ninety percent of infections arising in the first 14 days after delivery are of genital or urinary tract in origin Other causes include mastitis, wound infections (following caesarean section, episiotomy or perineal tears), venous thrombophlebitis and post general anaesthesia pneumonia; pneumonia is very rare after epidural anaesthesia during labour Puerperal infection of the uterus is a common cause of post-natal pyrexia (7) There is an increased risk of endometritis following prolonged rupture of membranes and instrumental delivery Infections are often polymicrobial, caused by a variety of organisms ascending from the vagina such as E coli, Streptococcus A or B, anaerobes, Bacteroides spp., Mycoplasma hominis and Ureaplasma urealyticum Post-partum endometritis should be suspected in women presenting with highgrade fever, lower abdominal pain, uterine tenderness and leucocytosis An antibiotic regimen consisting of clindamycin and an aminoglycoside is recommended Routine use of prophylactic antibiotics for elective and emergency caesarean sections is recommended by the U.K RCOG national guidelines The antibiotic used should be limited to one dose to reduce the possibility of resistance Viral Infections Rubella (German Measles) This is caused by an RNA togavirus and is acquired by respiratory droplet exposure After an incubation period of to weeks, a mild febrile illness with a macular rash, suboccipital and posterior auricular lymphadenopathy and arthralgia occur The affected individual is infectious for week before the onset of the rash until days afterwards The incidence of rubella infection has considerably reduced since the introduction of the rubella vaccine programme in most developed countries About 2% to 3% of women not respond to the rubella vaccine and therefore remain susceptible to the infection Rubella infection in pregnancy has marked embryopathic consequences to the fetus when acquired by the fetus in utero (8) Risk of transmission to the fetus with resultant congenital anomalies occurs is over 90% in the first trimester, dropping to about 35% by weeks 13 to 16 The range of congenital defects seen maybe permanent and includes cardiac anomalies (commonly patent ductus arteriosus or peripheral pulmonary artery stenosis), ocular defects (cataracts, glaucoma), microcephaly, developmental delay, sensorineural deafness, hepatosplenomegaly and thrombocytopaenic purpura The severity of these anomalies merits the offer of termination of pregnancy to the mother in cases where the fetus may be affected The predominant defects in first-trimester infection are cardiac disease and deafness whilst deafness alone is the main defect seen in second-trimester infection Congenital defects are rare with maternal infection after 16 weeks Maternal re-infection in immune women is usually subclinical and the risk to the fetus is thought to be relatively low (250/mm3 due to increased risk of serious rash or hepatotoxicity Elective caesarean section reduces the risk of vertical transmission by 50% when compared with that of planned vaginal delivery The risk is further reduced by 90% when combined with antiretroviral treatment It is effective even with low viral loads (1000 copies/mL) but additional benefit is uncertain in women taking HAART with undetectable viral loads In the United Kingdom, HIV-positive women who are on HAART are given the option of a vaginal delivery provided they have no detectable viraemia (95%) However, they not provide information on the subtype of influenza A virus Nucleic acid amplification tests, including rRT-PCR, are the most sensitive and specific influenza diagnostic tests but false negatives can occur and test results may take several days Not all nucleic acid amplification assays can specifically differentiate 2009 H1N1 influenza virus from other influenza A viruses If specific testing for 2009 H1N1 influenza virus is required, testing with an rRT-PCR assay specific for 2009 H1N1 influenza or viral culture should be performed As pregnant women are at increased risk of complications from H1N1 influenza, the U.K DOK and HPA recommend vaccination for pregnant women at any stage of pregnancy Two different types of vaccines have been licensed by the European Medicines Agency for use in the United Kingdom including pregnant women Pandemrix is preferred as it only requires one dose and gives more rapid protection than the two-dose Celvapan vaccine It contains inactivated virus components and an adjuvant, which boosts the immune response thereby reducing the dose of vaccine required As of the end of April 2010, pandemic influenza H1N1 activity has significantly reduced in the United Kingdom and remains low in much of the temperate zones The most active areas of transmission currently are parts of West and Central Africa, with some focal areas of activity in South East Asia and Central America (21) Bacterial Infections Syphilis Prevalence of syphilis in women of reproductive age varies from as high as 20% in some African populations to about 0.02% in high-income countries More than million cases of congenital syphilis occur worldwide every year The morbidity and mortality associated with congenital syphilis are preventable and antenatal screening and treatment of syphilis are extremely cost-effective interventions even when the prevalence of infection is very low Congenital syphilis is seen far less in the United Kingdom due to a well-established antenatal screening programme and low rates of syphilis in pregnant women, although rates are increasing Syphilis is a systemic chronic granulomatous infection caused by the spirochaete Treponema pallidum Antenatal syphilis poses a significant threat to both pregnancy and fetus T pallidum readily crosses the placenta, resulting in fetal infection Fetal infection can occur at any stage of maternal infection but is more common in primary and secondary syphilis (50%) when maternal spirochataemia is at its greatest, compared with early latent (40%) and late latent syphilis (10%) (22) Although infection may occur at any stage of pregnancy, it is most likely to arise after the 18th week of pregnancy when the fetus is able to mount an immune response Up to 50% of untreated maternal primary and secondary infections result in fetal loss (stillbirths and perinatal deaths) and 50% in preterm labour Other manifestations of fetal infection on ultrasound include intrauterine growth restriction, hydrops fetalis, polyhydramnios and hepatomegaly The majority of infected women are asymptomatic and are diagnosed following routine antenatal serological screening If non-treponemal antigen tests such as Venereal Diseases Research Laboratory (VDRL) tests are used as the initial screening test, this can be associated with biological false positive results Treatment of maternal infection should be undertaken in conjunction with obstetricians, midwives, paediatricians and genitourinary medicine specialists to ensure tracing of partners and prevention of re-infection The antibiotic of choice is high-dose benzathine penicillin G administered as a single intramuscular dose of 2.4 MU for primary, secondary and early latent syphilis and the same dose for three consecutive weeks for late latent syphilis Aqueous procaine penicillin may also be used but requires a longer course of daily treatment Penicillin is by far the preferred choice as it offers a cure rate in excess of 98% compared to non-penicillin alternatives, which are associated with failures of prevention of congenital infection in the neonate Therefore, desensitisation to penicillin in those reporting allergies should be considered Patents need to be warned that there is a greater risk of the Jarisch–Herxheimer reaction after treatment of early syphilis in pregnancy This may precipitate premature labour Erythromycin is associated with a lower cure rate and does not penetrate the placental barrier in adequate doses to treat the fetus Likewise, azithromycin is not recommended for similar reasons and there are also concerns regarding INFECTIONS IN PREGNANCY azithromycin-resistant strains Treatment of babies at birth with penicillin is recommended following maternal treatment with macrolides Mothers treated with a macrolide should be considered for retreatment with doxycycline after delivery and when breastfeeding is completed Tetracyclines should be avoided because of their potential effects on bone and dentition All neonates born to mothers with syphilis should be evaluated for congenital syphilis Diagnosis of congenital syphilis is made by demonstrating the presence of treponemes by dark ground microscopy and/or PCR of exudates from suspicious lesions or body fluids and by serology Serological tests detecting IgG may be positive due to passive transfer of maternal antibodies whether or not the infant is infected A positive anti-treponemal immunoglobulin M (IgM) enzyme immunoassay (EIA) test, a fourfold increase or more of the rapid plasma reagin (RPR) or VDRL titre or the T pallidum particle agglutination assay (TPPA) above that of the mother indicates a diagnosis of congenital infection Early clinical manifestations of congenital syphilis in newborns include rashes, vesiculobullous lesions, condylomata lata, hepatosplenomegaly, generalised lymphadenopathy, osteochondritis and later periostitis (especially of the long bones), which may present as pseudoparalysis, neurological involvement such as meningitis or chorioretinitis and thrombocytopaenia Late stigmata include interstitial keratitis, deafness, Clutton’s joints and gummata of the nasal septum, palate and throat Craniofacial malformations may be present with frontal bossing and a bulldog-like appearance with hypoplastic maxilla, high-arched palate and prominent mandible, saddle nose deformity and rhagades Dental deformities may manifest as Hutchinson’s incisors and mulberry molars Treatment of the infected neonate is with intravenous benzylpenicillin Group B Streptococcus Group B streptococcus is the most common cause of severe early-onset neonatal infection in the developed world It is also a leading cause of maternal chorioamnionitis and puerperal endometritis Group B streptococcus is found as a normal vaginal commensal in 25% of pregnant women Forty to seventy percent of infants born to colonised mothers become colonised in the first week of life with about 1% developing acute infection Neonatal infection can be classified as early onset (7 days) The majority of neonatal infections are early onset, presenting with sepsis, pneumonia or meningitis The mortality is 10% in this group being significantly higher in preterm infants The incidence of early-onset group B streptococcus disease in the United Kingdom is 0.5/1000 births (23) Intrapartum antibiotic prophylaxis to high-risk mothers has been shown to significantly reduce the risk of early-onset neonatal disease High-risk mothers can be identified by universal antenatal screening or a risk-based strategy Universal screening of pregnant women for group B streptococcus is not currently offered in the United Kingdom This is in contrast to the United States where the CDC recommends that all pregnant women undergo bacteriological screening, with vaginal and rectal swabs taken for group B streptococcus culture at 35 to 37 weeks’ gestation (24) Those found to be colonised with group B streptococcus are offered intrapartum antibiotic prophylaxis, usually in the form of high-dose intravenous benzylpenicillin or ampicillin which is continued until delivery With a risk-based strategy, management involves selective antibiotic prophylaxis to women deemed at risk Recognised risk factors for early-onset disease include preterm labour with preterm rupture of membranes, rupture of membranes >18 141 hours prior to delivery or pyrexia >388 in labour The U.K RCOG guidelines argue in favour of prophylaxis in the presence of two or more risk factors, when group B streptococcus is found incidentally in the vagina or in the urine in the current pregnancy and in women with a previous affected child (23) Protozoal Infections Toxoplasmosis Toxoplasmosis is caused by the protozoan parasite Toxoplasma gondii Domestic cats are the definitive hosts in which the parasite may complete its life cycle Infection is primarily acquired through ingestion of cysts in infected undercooked meat or by ingestion of oocysts in inadequately washed garden produce that has been contaminated with cat litter The U.K prevalence of maternal toxoplasma infection is low at around 2/1000 In the neonate, toxoplasmosis infection presents with chorioretinitis, microcephaly, hydrocephalus, intracranial calcification and mental retardation (25) Maternal primary infection is mostly asymptomatic Five to fifteen percent of infected women present with a glandular fever like illness with flu-like symptoms and lymphadenopathy The neurological presentation that can rarely result in an affected mother from cerebral toxoplasmosis is discussed later in this chapter Data from France, where the prevalence of toxoplasmosis is higher than the United Kingdom indicate that the risk of congenital infection increases with gestational age at maternal seroconversion The risk of transmission is 10% to 15% in the first trimester, 25% to 40% in the second trimester and over 60% in the third trimester In contrast, the risk of damage to the fetus is higher when infection occurs early in the first trimester Serological testing using T gondii IgG/IgM antibodies, a rise in IgG titres in serial samples and IgG avidity testing are used to diagnose maternal infection Once maternal infection is confirmed, treatment with spiramycin should be commenced to reduce the risk of vertical transmission and consideration should be given to fetal testing and treatment Fetal infection can be proven by amplification of T gondii DNA by PCR in amniotic fluid ideally at 18 weeks In cases of confirmed fetal infection or high risk to the fetus, for example, maternal seroconversion after 32 weeks, three weekly cycles of pyrimethamine, sulphadiazine and folinic acid alternating with spiramycin is recommended and continued until delivery Pyrimethamine is potentially teratogenic and should not be used in the first trimester of pregnancy Ultrasound surveillance for abnormalities should be undertaken to detect fetuses that have been affected Ultrasound abnormalities are a late sign and serial scans are needed The most common abnormality is ventricular dilatation, with other findings of intracranial calcification, hepatomegaly and placental thickening Absence of abnormality on ultrasound does not reliably predict whether an infected fetus will be unaffected Termination of pregnancy may be considered by couples before 24 weeks gestation on the basis of a positive result on PCR testing of amniotic fluid Parasitic Infections Malaria Malaria is the second most common cause of infectious disease-related death in the world after tuberculosis Although not common in the United Kingdom, malaria is commonly seen in women from developing countries and in immigrant populations of women who have travelled to endemic areas It is caused by the four species of Plasmodium that infect humans: vivax, ovale, malariae and falciparum P falciparum is associated with the worst prognosis The infection is transmitted by the bite of the female anopheline mosquito 142 NEUROLOGY AND PREGNANCY: CLINICAL MANAGEMENT The effects of malaria in pregnancy on the mother and fetus depend on the mother’s immunity derived from previous exposure to infection Women from non-endemic areas with no pre-existing immunity are more likely to be symptomatic when parasitaemic, and are at greater risk of developing severe disease and death In areas with moderate to high transmission rates, women have a high level of immunity to malaria that is maintained by continual exposure (26) This immunity is altered by pregnancy, especially in women in their first ongoing pregnancy with high parasite loads, although the risk is reduced with subsequent pregnancies Pregnant women are more likely to suffer from more severe disease compared with non-pregnant women In addition, pregnant women have an increased risk of symptomatic hypoglycaemia during Plasmodium infection and are more likely to suffer from severe anaemia as a result of placental sequestration of infected erythrocytes Adverse consequences of malaria in pregnancy include an increased risk of spontaneous abortion, stillbirth, preterm labour and low birth weight Malaria in non-immune pregnant women should be treated as an emergency, and these women should be admitted to hospital and monitored closely Selection of a specific drug for malarial treatment in pregnancy depends on any known regional drug sensitivities or resistance, severity of disease and safety of the drugs in pregnancy Uncomplicated chloroquineresistant falciparum malaria in pregnancy should be treated with quinine (27) Close observation including uterine and fetal heart monitoring for development of complications is necessary Quinine should be combined with a second drug, clindamycin rather than doxycycline, to ensure complete eradication of parasites Both drugs have a good safety record in pregnancy The side effects of quinine are tinnitus, dizziness and hypoglycaemia The RCOG guidelines state that atovaquone-proguanil (Malarone) and arthemeter-lumefantrine (Riamet) can be used as alternatives to quinine The U.S CDC guidelines are more cautious owing to concerns of lack of safety data in the first trimester and state that both treatments may be used if other treatment options are not available or if the potential benefit is judged to outweigh the benefits (28) Because of the possible association with mefloquine treatment during pregnancy and an increase in stillbirths, the CDC guidelines restrict its use to situations where there are no other treatments available Chloroquine is the drug of choice for treatment of the erythrocyte asexual forms for all non-falciparum malaria Chloroquine resistance to P vivax is an increasing problem since 1992 in the regions of Papua New Guinea and Indonesia The CDC and RCOG guidelines recommend the use of quinine as first line for suspected chloroquineresistant vivax infections Primaquine, which is used for the eradication of liver hypnozoites in P vivax and P ovale infections to prevent relapse, is contraindicated in pregnancy Pregnant women with these infections should be maintained on weekly chloroquine for the duration of the pregnancy and should be treated after delivery with primaquine Treatment in pregnancy may have lower efficacy than in non-pregnant patients and these women should be advised about the risk of recurrence Pregnant women from non-endemic areas and those originally from those areas but now residing elsewhere should be advised to avoid travelling to endemic areas, if possible for the duration of the pregnancy (29) If travel is unavoidable they should be advised to take antimalarial prophylaxis The CDC and RCOG guidelines recommend chloroquine or, if travelling to areas where chloroquine resistance is present, mefloquine should be used Its use at prophylactic doses during the second and third trimester is not associated with adverse fetal or pregnancy outcomes This should be combined with other preventative strategies such as avoiding mosquito bites by covering exposed skin, using insect repellents and insecticide-treated mosquito bed nets WHO recommends that pregnant women living in malaria-endemic areas should receive intermittent antimalarial chemoprophylaxis after 20 weeks’ gestation CNS INFECTIONS IN PREGNANCY Meningitis Bacterial Meningitis Bacterial meningitis has an annual incidence of to 10 cases per 100,000 adults and each year causes about 135,000 deaths worldwide Acute bacterial meningitis is a life-threatening medical emergency which may evolve rapidly in hours, and requires prompt recognition and treatment Lumbar puncture can be used to confirm the diagnosis in patients presenting with suspected meningitis but treatment should not be delayed if suspicion is high Imaging with MRI should be performed first in patients with new-onset seizures, an immunocompromised state, signs concerning for mass lesion or moderate or severe impairment of consciousness The clinical features and prognostic factors in adults with bacterial meningitis were recently reported in a study of 696 cases, none of whom were reported to be pregnant (30) The most common pathogens were Streptococcus pneumoniae (51%) and Neisseria meningitidis (37%) The classic triad of fever, neck stiffness, and a change in mental status was present in only 44% of episodes However, 95% had at least two of the four symptoms of headache, fever, neck stiffness and altered mental status Risk factors for an unfavourable outcome that are relevant to pregnancy were the presence of otitis/sinusitis, absence of rash, low score on Glasgow coma score on admission, tachycardia (>120 bpm), a positive blood culture, low CSF white cell count (WCC) (56) and decreased platelet count (