Perinatal mortality in the dog and cat is highly variableand includes deaths that occur during birth, immediately after birth and during the neonatal period, which goes from birth to the first four weeks of the neonate’s life. In dogs and cats, even more so than in other animal species, the neonatal period is particularly short and very critical,in view of both the adaptation phase to the extra-uterine environment and for the continuous functional and anatomical transformations underway.
Ranked by importance, in the neonatal periodinfectious diseases are the second leading cause of death and are responsible for a large percentage of neonatal losses, especially during the first two weeks of life; bacterial infections, in the puppy more than in the kitten, are the main culprit. These bacterial infections can be the cause of organ or tissue infections, but more often they result in septicaemia, which is often fatal in neonates. Septicaemia is therefore a formidable cause of morbidity and mortality in the neonatal period, even if, to date, its true prevalence has not been fully recognized and is probably underestimated.
Septicaemiais defined as an acute invasion of the circulatory system by bacterial pathogens that can cause sepsis or septic shock, with the possible involvement of different organs or tissues. In newborns of domestic species, septicaemia is a very common cause of morbidity and mortality, especially in subjects which have not taken sufficient amounts of colostrum or have taken colostrum of inadequate quality in the first 24 hours after birth.
AETIOPATHOGENESIS
While recognizingthe bacterial aetiology of this condition, neonatal septicaemia is often caused by germs that are also found in healthy neonates, germs that cause disease only when the balance between bacteria and host is altered by the presence of predisposing factors. In some cases, instead, the germs are particularly pathogenic and can be the cause of disease, sometimes also of considerable gravity, regardless of the negligible role of predisposing factors: such is the case ofneonatal infections caused by haemolytic Escherichia coli or by beta-haemolytic streptococci.
Neonates are vulnerable to infectious agents in view of the presence of immaturity of multiple organ systems, that also involves the immune system; the immune system of the newborn is in fact almost totally dependent on the passive transfer of immunity from the mother to the offspring via colostrum, the quali- quantitative characteristics of which determine its efficacy.
Various predisposing factors can alter the balance between bacteria and host; these may include environmental conditions and/or how the breeding facility or nursery is managed, parturition, maternal conditions or the neonates themselves. With regard to the environment, quite often the concept of hygiene is lessened to the concept of apparent cleanliness. Apart from the need for adequate cleaning and constant disinfection of the environment, it is in fact also essential to adjust the temperature, humidity and air conditioning according to the needs of the neonates. The importance of overcrowding and the failure to isolate the bitch at the end of gestation, at the moment of parturition and after parturition with its litter is also often underestimated. The role of human vectors should also be considered, together with the indiscriminate use of antibiotics that creates dangerous antibiotic-resistances and alters the natural and physiological bacterial colonization of the neonate. As for parturition, which in litter-bearing species is physiologically long, the prolongation of the expulsion phase and dystocia in general are correlated witha risk of foetal hypoxia and a greater susceptibility to neonatal infections. Among the maternal factors, in addition to the possible transmission of infections through the placenta or during parturition, in the presence of overt or subclinical cases of endometritis or mastitis, it is also known that neonates can also ingest (or just come in contact with) biological fluids characterized by the presence of a high bacterial load. The role of gastroenteritis, of oral cavity infections and of maternal dermatitis, which can also be the cause of bacterial infections in neonates, is instead underestimated. An inadequate quantitative or qualitative production of colostrum also implies an insufficient transfer of passive immunity to neonates, which become more vulnerable to infections. As for the neonates themselves, factors such as prematurity, low birth weight, prolonged hypoxia, hypothermia, hypoglycaemia and inadequate colostrum intake can all promote bacterial growth and increase the risk of septicaemia. The presence of any skin wounds, skin infections, conjunctivitis and omphalitis, in addition to pneumonia and enteritis, all constitute high-risk conditions favourable to the onset of septicaemia. In kittens, viral infections are a predisposing factor for the onset of secondary bacterial infections, which sometimes result in septicaemia. In puppies, neonatal infections caused by Herpesvirus canis by may be a direct cause of neonatal mortality or be a predisposing factor for the development of septicaemic conditions.
The bacteria which are more commonly isolated in puppies which die because of neonatal septicaemia are: Escherichia coli, streptococci, staphylococci (S. aureus), Klebsiella, Pseudomonas, Enterobacter, Proteus and anaerobes; in kittens Pasteurella has also been isolated.
In terms of pathogenesis, although septicaemia can develop from organ infections of the neonate itself, vertical transmission seems to be the major route of contamination and is responsible for over 60% of cases of neonatal septicaemia. Although transplacental contamination is possible, as well as trough the intake of infected milk, in most cases contaminations occur either at birth, during the passage through the birth canal, or in the postpartum period, due to contact of the neonates with vaginal discharge, even in the absence of overt maternal symptoms of endometritis. Maternal care as well, through licking, may contribute to the spread of germs from vaginal discharge or from the maternal oral cavity to the mouth, upper respiratory tract, navel or genitals of the neonates.
Another pathogenic mechanism also recognized in neonates is the phenomenon of "bacterial translocation", through which large amounts of bacteria are absorbed by the intestinal mucosa and enter into the bloodstream, causing, precisely, septicaemia. This event can be favoured by absorption abnormalities typical of the intestinal epithelium during the first hours after birth. To facilitate the absorption of colostral immunoglobulins, during the first hours after birth the intestinal epithelium is in fact particularly "permeable", a feature that is lost once the absorption of colostral antibodies has been completed, precisely to prevent the access of harmful macromolecules. Failed colostrum uptake is therefore a double problem for the neonate: the absence of maternal antibodies is worsened by the maintained vulnerability, which favours bacterial absorption and hence the risk of bacterial translocation.
CLINICAL SYMPTOMS
Although neonates of any age can be affected, septicaemia mainly affects puppies and kittens in the first week after birth. Neonatal septicaemia is usually a hyperacute condition, with sudden death due to septic shock or with deatha few hours after the onset of septicaemia, following a sudden and rapid deterioration in overall conditions. Septicaemia may however also present itself with variable clinical presentations, it can be acute or subacute, the latter characterized by a progressive deterioration of overall conditions and considered among the causes of the so-called "fading puppy syndrome". The symptoms are often non-specific and dependent on the more or less acute evolution of the disease. The onset is usually characterized by the reduction or disappearance of the sucking and swallowing reflex, by hypothermia, hypoglycaemia, whining and weakness. With the progression of the disease there is diarrhoea (which may at times appear as the first symptom), which can at times be haemorrhagic, abdominal pain, dyspnoea, oedema and petechial haemorrhages, up to a stage of torpor, haematuria or necrosis of the extremities (Figs. 1 and 2). This latter finding is the most typical component of neonatal septicaemia (but not necessarily present in all cases); in view of the circulatory damage caused by bacterial toxins there is a reduction in blood flow to the extremities (nose, claws, tail, the tip of the ears), hypoxia, vasculitis, even disseminated intravascular coagulation, and infarction, which initially result in a cyanotic colouring of the extremities and then culminate in necrosis and detachment of the necrotic segments. When organ or tissue infections are present (omphalitis, dermatitis, pneumonia, etc.), related specific symptoms are also present.
In most cases, in puppies and kittens apparently born healthy the onset of septicaemia takes place at the age of 2-4 days, leading to a rapid physical deterioration after the first 24-48 hours and death within 2-5 days after birth. In case of a later onset, at 1-2 weeks of age, septicaemia may be distinguished from viral infections for the speed (a few hours) of deterioration of the general physical conditions and for the almost sudden loss of appetite. The extraordinarily rapid evolution of septicaemia in neonates essentially depends on the limited defensive capabilities present, on the greater instability of blood glucose, aggravated by bacterial energy consumption, and on the exceptional pathogenicity of certain microbial agents.
DIAGNOSIS
Septicaemia should be included among the differential diagnoses in all cases of sudden neonatal death and in all female dogs (or breeding farms) with recurrent neonatal deaths. It would also be appropriate to consider septicaemia among the differential diagnoses even in cases of neonatal deaths resulting from the presence of a more or less rapid physical wasting. Whenever neonatal septicaemia is suspected, the clinical investigation must include the mother and all the siblings from the same litter; the opportunity to perform a bacteriological examination of the mother’s vaginal discharge, even if endometritis is not suspected, of mammary secretions, of the oral cavity, skin and rectum is to be considered.
The intravitam diagnosis of neonatal septicaemia is very difficult, both for the predominance of hyperacute forms with sudden death or with death within a few hours as well as for the impossibility of being able to perform the laboratory investigations necessary to confirm the possible clinical suspicion. Haemoculture, which requires repeated blood samples at short time intervals and a volume of at least 0.5-1 ml, is in fact impracticable in neonates of dogs and cats, because of the reduced body size. Swabs for bacteriological examination can be performed in puppies with diarrhoea, omphalitis, pyoderma or conjunctivitis.
The post-mortem examination is dependent on the appropriate preservation and timely delivery of the corpse to the reference centre where the necropsy will be performed, with the main goal of collecting samples for a culture-based investigation. The proper preservation of the corpse (immediate refrigeration and preservation at 5° C for a maximum of 48 hours) is essential to avoid cadaveric contamination and the phenomenon of a possible rapid post-mortem contamination, caused by the typical high water content of neonates and the usual high temperatures of the nursery. Although the sampling of numerous organs is recommended in scientific literature, culture investigations may be limited to the liver, kidney, lung, spleen and intestine, even in the absence of macroscopic lesions, to the heart and brain in the presence of evident lesions as well as to any possible abdominal or thoracic effusions. The swabs, with transport media (i.e. Amies with or without charcoal) (Fig. 3) and executed avoiding contaminations (Figs. 4 and 5), must be preserved at 4° C for no longer than 48 hours after collection.
The bacterial isolate (Fig. 6) must be accurately examined by experienced investigators and an antibiogram should be performed (Fig. 7) in order to prepare a more targeted therapy for the neonates of the same litter. It should be noted that often the presence of a bacterial isolate does not in itself necessarily imply a direct involvement in the neonatal disease or death; the correlation is only presumptive.
Only rarely are macroscopic changes found at necropsy, probably due to the hyperacute nature of most forms of neonatal septicaemia; apart from the absence of macroscopic lesions, the typical histological findings consist in the presence of germs in the deep tissues of the main target organs.
TREATMENT
Unfortunately, the prognosis of neonatal septicaemia in patients ad vitam is guarded or poor. However, whenever the evolution of the disease allows it, neonatal symptomatic and supportive care is possible while waiting, when possible, for culture results and antibiotic susceptibility tests in order to set up a targeted causal treatment. It should however be recalled that also in such cases the prognosis remains guarded. The affected neonate must be removed from the litter, for a better management of the patient, while isolation in an attempt to prevent the possible spread of the disease to other littermates remains controversial.
With regard to antibiotic therapy, the waiting times for culture tests and the antibiogram contrast with the need to start an immediate antimicrobial therapy in neonates with suspected septicaemia. For this reason, while waiting for the results of diagnostic studies therapy should be started using a broad-spectrum, easily manageable and easy-to-use antibiotic. In view of these requirements, the first choice therapy includes the use of third-generation cephalosporins, among which the use of ceftiofur is recommended, at the dose of 2.5 mg/kg/bid subcutaneously administered up to 48 hours after remission of symptoms.
Should neonates not be able to eat, isolation from the other littermates is recommended, in order to allow a better therapeutic management of the patient and to prevent the phenomenon of maternal cannibalism induced by the hypovitality of the puppies or kittens. Symptomatic therapy and supportive care, aimed at contrasting the effects of septicaemia, include the control of body temperature, dietary support and/or fluid therapy and, in the attempt to improve the neonate’s immune system, the administration of serum, whose real usefulness is still in question.
PREVENTION
In view of the severity of the disease, which is often fatal in spite of therapeutic attempts, the main intervention available to control neonatal septicaemia is prevention, based on the elimination or reduction of predisposing factors. First, all environmental and management risk factors should be eliminated and, subsequently, an attempt should be made to try to reduce existing maternal-related factors. As for the environment, overcrowding should be avoided, as well as promiscuity among mother cats or dogs; the hygiene of premises and of equipment should be guaranteed through periodic and thorough disinfection; the use of irritating substances for neonates, via inhalation or contact, should however be avoided. Breeding females must be selected taking into account not only the appropriate correspondence with breed standards or work attitude but also the so-called "maternal instinct", meant broadly to include not only a positive maternal behaviour but also the absence of hereditary defects, good fertility and prolificacy, absence of problems at parturition and in the postnatal period and no medical history of stillbirth or neonatal mortality beyond the maximum acceptable rate (10%).
Medical and breeding management prophylaxis must include an adequate dietary and vaccination plan, periodic antiparasitary prophylactic treatments and control of the conditions of the oral cavity and skin. In females with a history of neonatal mortality, either occasional or recurrent, with the bacterial cause identified or suspected, a vaginal bacterial culture is recommended, possibly repeated during mating and during the last ten days of pregnancy, or only in the 10 days preceding parturition, possibly in combination with the cultural examination of mammary secretions, if present. Should the culture be positive, depending on the germ isolated and on the extent of bacterial growth a treatment with antibiotics should be implemented, chosen based on the antibiogram and on the possibility of use in late pregnancy. The goal of this pharmacological intervention, to be implemented in the last 5-7 days of gestation and, when possible, also intrapartum, is to reduce the microbial load of the birth canal and thus limit the contagion of puppies/kittens during transit at the time of birth. If parturition takes place in inadequate environmental conditions or if neonates suffering from hypoxia are present,treatment of the neonates considered "at risk" is indicated using cephalexin (10-20 mg/kg/bid), treatment to be performed within 2 hours after birth and continued for the first 5 days of life. It is essential to stress that these preventive measures should be used only in cases of real necessity, in order to avoid alarming phenomena of antimicrobial resistance and multi-resistance, and that they do not always allow the prevention of neonatal septicaemia.
Suggested reading
- Veronesi MC, Castagnetti C, Taverne MAM. Neonatologia veterinaria. EdiSES, Napoli 2013.
- Munnich A, Lubke-Becker A. Escherichia coli infections in newborn puppies - Clinical and epidemiological investigations. Theriogenology 2004;62:562-575.
- Schafer-Somi S, Spergser J, Breitenfellner J, Aurich JE. (2003): Bacteriological status of canine milk and septicaemia in neonatal puppies - A retrospective study. J Vet Med B 2003;50:343-346.
- Meloni T, Martino PA., Grieco V, Pisu MC, Banco B, Rota A, Veronesi MC. (2014) A survey on bacterial involvement in neonatal mortality in dogs. Veterinaria Italiana 2014. Accepted for publication.