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There are currently no blood tests for diagnosing tetanus. The diagnosis is based on the presentation of tetanus symptoms and does not depend upon isolation of the bacterium, which is recovered from the wound in only 30% of cases and can be isolated from patients without tetanus. Laboratory identification of "C. tetani" can be demonstrated only by production of tetanospasmin in mice. Having recently experienced head trauma may indicate cephalic tetanus if no other diagnosis has been made.
The "spatula test" is a clinical test for tetanus that involves touching the posterior pharyngeal wall with a soft-tipped instrument and observing the effect. A positive test result is the involuntary contraction of the jaw (biting down on the "spatula") and a negative test result would normally be a gag reflex attempting to expel the foreign object. A short report in "The American Journal of Tropical Medicine and Hygiene" states that, in a patient research study, the spatula test had a high specificity (zero false-positive test results) and a high sensitivity (94% of infected patients produced a positive test).
Unlike many infectious diseases, recovery from naturally acquired tetanus does not usually result in immunity to tetanus. This is due to the extreme potency of the tetanospasmin toxin. Tetanospasmin will likely be lethal before it will provoke an immune response.
Tetanus can be prevented by vaccination with tetanus toxoid. The CDC recommends that adults receive a booster vaccine every ten years, and standard care practice in many places is to give the booster to any patient with a puncture wound who is uncertain of when he or she was last vaccinated, or if he or she has had fewer than three lifetime doses of the vaccine. The booster may not prevent a potentially fatal case of tetanus from the current wound, however, as it can take up to two weeks for tetanus antibodies to form.
In children under the age of seven, the tetanus vaccine is often administered as a combined vaccine, DPT/DTaP vaccine, which also includes vaccines against diphtheria and pertussis. For adults and children over seven, the Td vaccine (tetanus and diphtheria) or Tdap (tetanus, diphtheria, and acellular pertussis) is commonly used.
The World Health Organization certifies countries as having eliminated maternal or neonatal tetanus. Certification requires at least two years of rates of less than 1 case per 1000 live births. In 1998 in Uganda, 3,433 tetanus cases were recorded in newborn babies; of these, 2,403 died. After a major public health effort, Uganda in 2011 was certified as having eliminated tetanus.
In 2000 neonatal tetanus was responsible for about 14% (215,000) of all neonatal deaths. In 2008 59,000 newborns worldwide died as a result of neonatal tetanus. In 2005, 57 countries were identified as still at risk, with 27 countries accounting for 90% of cases. As of December 2013 the number of countries at risk was reduced to 25.
The spores which cause tetanus are present everywhere, so the only prevention is immunization. Three properly spaced doses of tetanus toxoid vaccine are recommended for women of childbearing age, either before or during pregnancy; this will protect their future babies from neonatal tetanus after delivery.
Babies born from mothers with symptoms of Herpes Simplex Virus (HSV) should be tested for viral infection. Liver tests, complete blood count (CBC), cerebrospinal fluid analyses, and chest X-ray should all be completed to diagnose meningitis. Samples should be taken from skin, conjunctiva (eye), mouth and throat, rectum, urine, and the CSF for viral culture and PCR analysis with respect to the sample from CSF.
Standard titer measles vaccine is recommended at 9 months of age in low-income countries where measles infection is endemic and often fatal. Many observational studies have shown that measles-vaccinated children have substantially lower mortality than can be explained by the prevention of measles-related deaths. Many of these observational studies were natural experiments, such as studies comparing the mortality before and after the introduction of measles vaccine and other studies where logistical factors rather than maternal choice determined whether a child was vaccinated or not.
These findings were later supported in randomized trials from 2003 to 2009 in Guinea-Bissau. An intervention group of children given standard titer measles vaccine at 4.5 and 9 month of age had a 30% reduction in all-cause mortality compared to the children in the control group, which were only vaccinated against measles at 9 month of age.
In a recent WHO-commissioned review based on four randomized trials and 18 observational studies, it was concluded that "There was consistent evidence of a beneficial effect of measles vaccine, although all observational studies were assessed as being at risk of bias and the GRADE rating was of low confidence. There was an apparent difference between the effect in girls and boys, with girls benefitting more from measles vaccination", and furthermore "estimated effects are in the region of a halving of mortality risk" and "if these effects are real then they are not fully explained by deaths that were established as due to measles". Based on the evidence, the WHO's Strategic Advisory Group of Experts on Immunization concluded that "the non-specific effects on all-cause mortality warrant further research".
A lumbar puncture (LP) is necessary to diagnose meningitis. Cerebrospinal fluid (CSF) culture is the most important study for the diagnosis of neonatal bacterial meningitis because clinical signs are non-specific and unreliable. Blood cultures may be negative in 15-55% of cases, deeming it unreliable as well. However, a CSF/blood glucose ratio below two-thirds has a strong relationship to bacterial meningitis. A LP should be done in all neonates with suspected meningitis, with suspected or proven sepsis (whole body inflammation) and should be considered in all neonates in whom sepsis is a possibility. The role of the LP in neonates who are healthy appearing but have maternal risk factors for sepsis is more controversial; the yield of the LP in these patients may be low.
Early-onset is deemed when infection is within one week of birth. Late-onset is deemed after the first week.
The live attenuated BCG vaccine developed against tuberculosis has been shown to have strong beneficial effects on the ability to combat non-tuberculosis infections.
Several studies have suggested that BCG vaccination may reduce atopy, particularly when given early in life. Furthermore, in multiple observational studies BCG vaccination has been shown to provide beneficial effects on overall mortality. These observations encouraged randomised controlled trials to examine BCG vaccination's beneficial non-specific effects on overall health. Since BCG vaccination is recommended to be given at birth in countries that have a high incidence of tuberculosis it would have been unethical to randomize children into 'BCG' vs. 'no BCG' groups. However, many low-income countries delay BCG vaccination for low-birth-weight (LBW) infants; this offered the opportunity to directly test the effect of BCG on overall mortality.
In the first two randomised controlled trials receipt of BCG+OPV at birth vs. OPV only ('delayed BCG') was associated with strong reductions in neonatal mortality; these effects were seen as early as 3 days after vaccination. BCG protected against sepsis as well as respiratory infections.
Among BCG vaccinated children, those who develop a BCG scar or a positive skin test (TST) are less likely to develop sepsis and exhibit an overall reduction in child mortality of around 50%.
In a recent WHO-commissioned review based on five clinical trials and nine observational studies, it was concluded that "the results indicated a beneficial effect of BCG on overall mortality in the first 6–12 months of life. Relevant follow-up in some of the trials was short, and all of the observational studies were regarded as being at risk of bias, so the confidence in the findings was rated as very low according to the GRADE criteria and "There was a suggestion that BCG vaccination may be more beneficial the earlier it is given". Furthermore, "estimated effects are in the region of a halving of mortality risk" and "any effect of BCG vaccine on all-cause mortality is not likely to be attributable to any great extent to fewer deaths from tuberculosis (i.e. to a specific effect of BCG vaccine against tuberculosis)". Based on the evidence, the WHO's Strategic Group of Experts on Immunization concluded that "the non-specific effects on all-cause mortality warrant further research".
The current clinical case definition of diphtheria used by the United States' Centers for Disease Control and Prevention is based on both laboratory and clinical criteria.
Neonatal sepsis of the newborn is an infection that has spread through the entire body. The inflammatory response to this systematic infection can be as serious as the infection itself. In infants that weigh under 1500 g, sepsis is the most common cause of death. Three to four percent of infants per 1000 births contract sepsis. The mortality rate from sepsis is near 25%. Infected sepsis in an infant can be identified by culturing the blood and spinal fluid and if suspected, intravenous antibiotics are usually started. Lumbar puncture is controversial because in some cases it has found not to be necessary while concurrently, without it estimates of missing up to one third of infants with meningitis is predicted.
The susceptibility to risk of infection and immune deficiencies are active areas of research. Studies regarding the role of viruses in neonatal infections are lacking. Research also continues into the role and protective effect of gut, skin and other human microbiomes and the colonization during the neonatal period. The comparison between resource rich countries and resource poor countries makes it somewhat difficult to compare the diagnosis success since industrialized regions are able to confirm the diagnosis and presence of pathogens in the clinical laboratory. Clinical testing may not be available in all settings and clinicians must rely on the signs of infection in the newborn. Research data from Africa and Southeast Asia is scarce.
The result of some research has been the identification of diagnostic tools and procedures that could identify mothers with group B streptococcus infection in resource-poor regions. These procedures would be easy and inexpensive to use. Those mothers who are identified as being infected could then be prophylactly treated prior to the birth of the baby.
Probiotic administration of Lactobacillus species has shown some success.
A GBS vaccine is currently being tested but not currently available. Vaccination is estimated to being able to prevent 4% of GBS infections for preterm births and 60–70% for neonatal GBS infections in the US. The projected benefits of maternal vaccination is the prevention of 899 cases of GBS disease and 35 deaths among infants. The cost savings in the prevention of GBS may be over 43 million dollars. Vaccination may be especially beneficial in low to middle income countries where screening and prophylactic treatment is not possible. Analysts project that GBS vaccination would prevent 30–54% of infant GBS cases. Screening, prophylactic antibiotics and vaccine would prevent 48% of infection.
Polymerase chain reaction (PCR) assays have been proven to be more sensitive than either LAT or culture tests, and highly specific. However, PCR assays have not yet become routine in clinical settings. Countercurrent immunoelectrophoresis has been shown to be an effective research diagnostic method, but has been largely supplanted by PCR.
The latex particle agglutination test (LAT) is a more sensitive method to detect "H. influenzae" than is culture. Because the method relies on antigen rather than viable bacteria, the results are not disrupted by prior antibiotic use. It also has the added benefit of being much quicker than culture methods. However, antibiotic sensitivity testing is not possible with LAT alone, so a parallel culture is necessary.
Empirical treatment should generally be started in a patient in whom suspicion of diphtheria is high.
Neonatal sepsis screening:
1. DLC (differential leukocyte count) showing increased numbers of polymorphs.
2. DLC: band cells > 20%.
3. increased haptoglobins.
4. micro ESR (Erythrocyte Sedimentation Rate) titer > 15mm.
5. gastric aspirate showing > 5 polymorphs per high power field.
6. newborn CSF (Cerebrospinal fluid) screen: showing increased cells and proteins.
7. suggestive history of chorioamnionitis, PROM (Premature rupture of membranes), etc...
Culturing for microorganisms from a sample of CSF, blood or urine, is the gold standard test for definitive diagnosis of neonatal sepsis. This can give false negatives due to the low sensitivity of culture methods and because of concomitant antibiotic therapy. Lumbar punctures should be done when possible as 10-15% presenting with sepsis also have meningitis, which warrants an antibiotic with a high CSF penetration.
CRP is not very accurate in picking up cases.
In 2012, the World Health Organization estimated that vaccination prevents 2.5 million deaths each year. If there is 100% immunization, and 100% efficacy of the vaccines, one out of seven deaths among young children could be prevented, mostly in developing countries, making this an important global health issue. Four diseases were responsible for 98% of vaccine-preventable deaths: measles, "Haemophilus influenzae" serotype b, pertussis, and neonatal tetanus.
The Immunization Surveillance, Assessment and Monitoring program of the WHO monitors and assesses the safety and effectiveness of programs and vaccines at reducing illness and deaths from diseases that could be prevented by vaccines.
Vaccine-preventable deaths are usually caused by a failure to obtain the vaccine in a timely manner. This may be due to financial constraints or to lack of access to the vaccine. A vaccine that is generally recommended may be medically inappropriate for a small number of people due to severe allergies or a damaged immune system. In addition, a vaccine against a given disease may not be recommended for general use in a given country, or may be recommended only to certain populations, such as young children or older adults. Every country makes its own vaccination recommendations, based on the diseases that are common in its area and its healthcare priorities. If a vaccine-preventable disease is uncommon in a country, then residents of that country are unlikely to receive a vaccine against it. For example, residents of Canada and the United States do not routinely receive vaccines against yellow fever, which leaves them vulnerable to infection if travelling to areas where risk of yellow fever is highest (endemic or transitional regions).
At present this can only be made definitively by liver biopsy or post mortem examination. Given the isolation of a causative virus it should soon be possible to diagnose this by serology, polymerase chain reaction or viral culture. On necropsy, the liver will be small, flaccid, and "dish-rag" in appearance. It has a mottled and bile stained surface. On microscopy there is marked centrilobular to midzonal hepatocellular necrosis and a mild to moderate mononuclear infiltrate. Mild to moderate bile duct proliferation may also be present. On radiology, the liver may be shrunken and difficult to visualize on ultrasound. Ascites may be present.
The most characteristic feature are elevated levels of gamma glutamyl transferase (100–300 IU/L), aspartate transaminase (>1000 IU/L) and sorbitol dehydrogenase, with AST levels > 4000 IU/L indicating a poor prognosis. High levels of unconjugated and total bilirubin, and serum bile acids, can be seen. Moderate to severe acidosis, leukocytosis, polycythaemia, increased creatine kinase and hyperammonemia may be present, and hemolysis can occur at the end stage. The prothrombin time (PT) and partial thromboplastin time (PTT) is often prolonged. Subclinical horses may only show elevated liver enzymes without any other clinical signs. Horses are rarely hypoglycemic, but blood glucose monitoring is ideal to indicate which horses may be benefited by glucose treatment.
Note that, in neonates, sepsis is difficult to diagnose clinically. They may be relatively asymptomatic until hemodynamic and respiratory collapse is imminent, so, if there is even a remote suspicion of sepsis, they are frequently treated with antibiotics empirically until cultures are sufficiently proven to be negative. In addition to fluid resuscitation and supportive care, a common antibiotic regimen in infants with suspected sepsis is a beta-lactam antibiotic (usually ampicillin) in combination with an aminoglycoside (usually gentamicin) or a third-generation cephalosporin (usually cefotaxime—ceftriaxone is generally avoided in neonates due to the theoretical risk of kernicterus.) The organisms which are targeted are species that predominate in the female genitourinary tract and to which neonates are especially vulnerable to, specifically Group B Streptococcus, "Escherichia coli", and "Listeria monocytogenes" (This is the main rationale for using ampicillin versus other beta-lactams.) Of course, neonates are also vulnerable to other common pathogens that can cause meningitis and bacteremia such as "Streptococcus pneumoniae" and "Neisseria meningitidis". Although uncommon, if anaerobic species are suspected (such as in cases where necrotizing enterocolitis or intestinal perforation is a concern, clindamycin is often added.
Granulocyte-macrophage colony stimulating factor (GM-CSF) is sometimes used in neonatal sepsis. However, a 2009 study found that GM-CSF corrects neutropenia if present but it has no effect on reducing sepsis or improving survival.
Trials of probiotics for prevention of neonatal sepsis have generally been too small and statistically underpowered to detect any benefit, but a randomized controlled trial that enrolled 4,556 neonates in India reported that probiotics significantly reduced the risk of developing sepsis. The probiotic used in the trial was "Lactobacillus plantarum".
A very large meta-analysis investigated the effect of probiotics on preventing late-onset sepsis (LOS) in neonates. Probiotics were found to reduce the risk of LOS, but only in babies who were fed human milk exclusively. It is difficult to distinguish if the prevention was a result of the probiotic supplementation or if it was a result of the properties of human milk. It is also still unclear if probiotic administration reduces LOS risk in extremely low birth weight infants due to the limited number of studies that investigated it. Out of the 37 studies included in this systematic review, none indicated any safety problems related to the probiotics. It would be beneficial to clarify the relationship between probiotic supplementation and human milk for future studies in order to prevent late onset sepsis in neonates.
A "vaccine-preventable disease" is an infectious disease for which an effective preventive vaccine exists. If a person acquires a vaccine-preventable disease and dies from it, the death is considered a vaccine-preventable death.
The most common and serious vaccine-preventable diseases tracked by the World Health Organization (WHO) are: diphtheria, "Haemophilus influenzae" serotype b infection, hepatitis B, measles, meningitis, mumps, pertussis, poliomyelitis, rubella, tetanus, tuberculosis, and yellow fever. The WHO reports licensed vaccines being available to prevent, or contribute to the prevention and control of, 25 vaccine-preventable infections.
The disease incidence varies widely depending on the geographical location. The most extensive epidemiological survey on this subject has been carried out by Dharmasena et al. who analysed the number of neonates who developed neonatal conjunctivitis in England from 2000 to 2011. In addition to the incidence of this sight threatening infection they also investigated the time trends of the disease. According to them the incidence of Neonatal conjunctivitis (Ophthalmia Neonatorum) in England was 257 (95% confidence interval: 245 to 269) per 100,000 in 2011.
The symptoms of neonatal hepatitis are similar to another infant liver disease, biliary atresia, in which the bile ducts are destroyed for reasons that are not understood. The infant with biliary atresia is also jaundiced and has an enlarged liver, but is growing well and does not have an enlarged spleen. These symptoms, along with a liver biopsy and blood tests, are needed to distinguish biliary atresia from neonatal hepatitis.
Antibiotic ointment is typically applied to the newborn's eyes within 1 hour of birth as prevention against gonococcal ophthalmia. This maybe erythromycin, tetracycline, or silver nitrate.
There is no specific treatment for neonatal hepatitis. Vitamin supplements are usually prescribed and many infants are given phenobarbital, a drug used to control seizures, but which also stimulates the liver to excrete additional bile. Formulas containing more easily digested fats are also given to the infant.
Neonatal hepatitis caused by the hepatitis A virus also usually resolves itself within six months, but cases that are the result of infection with the hepatitis B or hepatitis C viruses most likely will result in chronic liver disease. Infants who develop cirrhosis ultimately will need a liver transplant.
This depends on the age of the animal affected and the efficiency of its immune system.
Colostral protection lasts up to 5 months of age, after which it decreases to an all-time low to increase yet again at about 12 months of age.
- Prenatal infection: virus travels from infected mother to fetus via the placenta. In this case, the time of gestation determines the result of the infection.
- If the fetus is infected in the first 30 days of fetal life, death and absorption of all, or some of the fetuses may occur. In this case, some immunotolerant healthy piglets may be born.
- If the infection happens at 40 days, death and mummification may occur. Also in this case, some or all the fetuses are involved, i.e. some of the fetuses can be born healthy and immunotolerant, or else carriers of the disease.
- If the viruses crosses the placenta in the last trimester, neonatal death may occur, or the birth of healthy piglets with a protective pre-colostral immunity.
- Postnatal infection (pigs up to 1 year of age): Infection occurs oro-nasally, followed by a viremic period associated with transitory leucopenia.
- Infection in adults (over 1 year of age): These subject would have an active, protective immune system which protects them from future exposures (e.g. mating with an infected male).
Therefore, it is important to note that the virus is particularly dangerous for the sow in her first gestation, which would be at 7–8 months of age, as she would have a particularly low antibody count at this age and could easily contract the virus via copulation.