If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Antisecretory Factor in the form of Salovum was given perorally as 2 sachets (Group A) and 4 sachets ((Group B) to children 6–24 months of age presenting with diarrhea.
Eighty percent of the patients in Group B responded with a firm faecal consistency 30 min after the end of the Salovum treatment, while 30% of the patients in Group A (2 sachets) responded likewise, p = 0.004.
The number of diarrheal stools decreased over this time from seven to one/two over 4 hours in the two groups (p = 0.234). None of the forty patients reported with any new episodes of diarrhea during the follow-up period.
No adverse effects were noted.
Diarrheal illnesses in young children cause morbidity and preventable deaths in developing countries. We evaluated two high doses of Salovum® [Antisecretory Factor] to treat diarrhea in young children and followed up for recurrence 6 weeks post treatment.
Forty children, 6-24 months old, admitted with acute diarrhea, to the Outpatient Department of Children’s Hospital in Lahore, Pakistan were selected. The patients were randomly allocated to either Group A given 2 sachets, or to Group B, given 4 sachets. Each sachet contained 4 gram of Salovum® and was mixed with Oral Rehydration Salt solution. This mixture was administered perorally within the first 30 min of treatment. The trained nursing staff observed them for number of stools and consistency over every half hour for a total of 4 hours. Follow up for 6 weeks was done daily by telephone, or visits by the mothers. The results demonstrate that Salovum provides a protective effect irrespective of the diarrhea causes.
Group B, given 4 sachets of Salovum® showed improved fecal consistency in 80% of the children compared to 50% in Group A within 30 minutes of treatment, p = 0.004. The number of diarrheal stools decreased over this time from seven to one/two over 4 hours in the two groups [p = 0.234]. None of the children showed a recurrence of diarrhea over the follow up period.
Peroral high doses of Salovum® rapidly and safely counteract diarrhea in children followed by a diarrhea-free period of 6 weeks.
Diarrheal disease of various etiologies is one of the leading causes of infant morbidity and mortality in developing countries. More than one million deaths from diarrhea are reported each year (UNICEF. The state of the world’s children 2016). Nearly 15% of the acute diarrheal episodes have been shown to continue for a longer duration going into persistent/chronic diarrhea and later into a chronic stage. Such development of chronic diarrhea often has a fatal outcome, or leads to severe and longstanding sequelae, with a total, negative impact on the time needed for a sufficient rehabilitation period (
Specific medical intervention of the diarrhea induced dehydration can be effectively and rapidly performed by means of oral rehydration solutions or by an adequate intravenous therapy. In most rural areas in developing countries, however, this form of therapy is not available for several reasons including economics. Moreover, various forms of vaccination programs against childhood diarrhea have, worldwide, demonstrated a rather limited progress. This restricted progress is probably caused by the multiple varieties of pathogenic agents causing pathological intestinal secretion. Thus; there is an urgent need for effective and specific treatment schedules, capable of a rapid and effective treatment for all forms of agents causing childhood diarrheal disease.
The Antisecretory Factor [AF] is an endogenously produced protein found in all mammalian tissues investigated so far. AF is secreted into blood, milk and bile (
). A registration of the children’s health status, with a focus on diarrheal diseases recurrence during the diarrhea rehabilitation period has, however, not been performed.
The primary objective was to achieve an early recovery from diarrheal illness in children from 6-24 months of age using two different doses of Salovum. The secondary objective was to document the recurrence of diarrhea in these children 6 weeks post treatment of the acute diarrheal episode. The aim was to keep these children free from recurrence of diarrheal disease, thereby eliminating the risk for the development of chronic diarrhea, malnutrition and/or death.
Material and methods
Children, 6-24 months of age, were selected from the Outpatients Department [OPD] of the Children’s Hospital, Lahore over a period of 12 months covering the diarrheal seasons from March 2016 to March 2017.
The desired number of children included in the study was obtained after screening from 68 children reporting acute watery diarrhea. All children between the ages of 6 to 24 months who had reported with a history of passage of 3, or more than 3, watery stools during the last 24 hours only and did not show any signs of moderate to severe dehydration were included. Patients with a history of taking antibiotics or anti-diarrheal drugs previously were excluded. They were also screened for any known allergy to eggs. Twenty-eight children were excluded based on the above inclusion criteria and refusal [n = 2] to participate in the study. Forty children were then randomized to either of the groups A or B with two doses of AF [Figure 1]. The nursing staff, but not the pediatricians, were blinded to the treatment groups. The number and consistency of stools were noted every half hour during the stay in the OPD by a trained group of senior nurses. Any vomiting or refusal to drink was also noted. The nurses were supervised by the pediatrician on call.
At a 95% confidence interval, assessing at a power of 90% for obtaining a consistency of stools with a difference of 50% as a successful outcome initially in the two groups, we calculated a sample size of 20 in each group (
). All of the children received the standard diarrheal treatment as outpatients.
Simple random sampling by computer generation of random numbers was used. Two groups of patients were allocated to either 2 sachets, 8 gram [Group A] – or to 4 sachets, 16 gram [Group B] of Salovum. Each sachet contained 4 grams of the spray dried egg yolk Salovum. Thus, the treatment started with either 2 sachets or 4 sachets of Salovum mixed together with 300 ml of Oral Rehydration Solution [ORS] and given perorally to the diarrhea patient during a 30 min long start up period using a cup and a spoon.
Data collection method
The Ethics Committee of the Children’s Hospital approved the study. The investigators obtained a signed consent from the parent/s of the identified patient after providing them with complete information regarding the treatment with Salovum. They were then placed into the group given either 2 sachets or 4 sachets of Salovum. The nurses were responsible for preparing them with 300 ml of ORS and immediately thereafter administered perorally using a sterilized steel spoon to the patient during a 30 min long period. During this period, the number of stools as well as consistency of stools was registered by the nurse observing the patients’ diapers and asking the mothers. The mothers, if breastfeeding, continued to do so. The children not breast-fed were allowed to take formula milk/semi solids with cup and spoon prepared by the nurses during the time of stay. All forms of standard diarrheal treatment continued as per protocol of the OPD. After the child was clinically stabilized, the number of stools reduced and the consistency improved over the 4 hours period, the patients were sent home with a mobile phone contact with the hospital.
The follow up contact consisted of a daily conversation between the nurse in-charge and the mothers via the mobile phone. Furthermore, the mothers were asked to immediately call if the child once more had developed acute diarrhea. During the following 6 weeks, follow up was done on a daily basis for all the patients.
The background data of the study children was achieved by bivariate analysis. The numbers and consistency of stools were compared before and after the peroral Salovum treatment in the two groups using a t-test/Wilcoxson’s Rank sum test for differences in the means of the two groups and a Chi Square test for differences in the proportions. The alpha level was defined at 0.05 in two tails. SPSS version 24 was used for analysis.
Baseline demographic and clinical characteristics of the two groups of selected patients are shown in Table 1. Significantly more females [80%] were in group B [4 sachets] than in group A [50%, 2 sachets], p = 0.0495. The age of the patients was also significantly higher [16.35 ± 6.59 months] in Group B than in Group A [11.40 ± 4.97 months], p = 0.011. The nutritional status was examined in terms of the weight for age and height/length for age and presented as Z scores using the WHO standards for growth (
). The mean WAZ and HAZ scores were not different in the two groups [p = 0.398 and p = 0.2189]. The patients in the two groups reported similar mean numbers of stools passed during the last 24 hours, varying from 7.1–7.5. The consistency of the stools was the same in Group A [95%] and in Group B [90%], i.e., loose or loose and watery, at the start of the peroral Salovum treatment [p = 0.553]. One patient from Group A and two patients from group B had reported an episode of vomiting before reporting to the hospital [data not shown].
Table 1Descriptive analysis of the baseline demographic and clinical characteristics of patients selected in the two groups, Group A (given 2 sachets) and Group B (given 4 sachets) of Salovum for the diarrhea study.
Group A (n = 20)
Group B (n = 20)
Males, n (%)
Females n (%)
Age in months, Mean ± SD
11.40 ± 4.97
16.35 ± 6.59
Weight for age (Z scores) Mean ± SD
-1.0645 ± 1.440
-1.435 ± 1.29
Length/Height for Age (Z scores) Mean ± SD
-0.3980 ± 1.889
-1.10 ± 1.647
No. of loose, watery stools at the time of reporting Mean ± SD
7.1 ± 2.8
7.5 ± 3.0
Consistency of stools at the time of reporting, n (%)
Note: The significance testing was done using either t-test or Wilcoxon’s Rank Sum test for two independent samples or a Chi Square test or Fisher’s exact test for differences in two proportions, with significance level at 0.05 in two tails.
The consistency of the stools rapidly changed from loose to firm and normal within 30 min after finishing of the peroral treatment with Salovum. The results demonstrated in Figure 2 showed that about 80% of the patients in Group B [4 sachets] responded with a firm fecal consistency already 30 min after the end of the Salovum treatment, while less than 30% of the patients in Group A [2 sachets] responded likewise, p = 0.004. The transformation of loose into firm stools continued in both groups over each of the coming next 30 minutes during the 4-hr-long registration period. The last stool registration was performed after 4 hrs. Thereafter the patients were sent home, but with a mobile phone contact with the hospital.
Figure 3 shows the proportion of children with diarrheal stools reduced as the proportion of children without diarrhea increased with time, measured every half hour while still in the OPD. The initial differences in the proportions were not significantly different in the two groups given either two times or four times the original dose of Salovum [p = 0.2347]. With time, the number of stools had reduced, but also the consistency had changed significantly.
The results in Figure 4 demonstrate the decrease in the mean numbers of stools, whether diarrheal or normal stools, reported at the start and at various times during the next 24 hours, after 3 days, 1 week and 6 weeks long rehabilitation period. After the initial 30–90 minutes, the stools reported by the mothers were of firm consistency and did not exceed more than one during the follow-up period. During this period, none of the children had reported with any recurrence of diarrheal disease. No adverse effects were noted during the stay in the OPD or during the 6 week long follow up period.
The present study showed how the endogenous protein AF efficiently terminated diarrhea in young children 6-24 months of age while being treated at the OPD clinic during a period of 4 hours after an initial dose of Salovum in 2 times or 4 times the original dose of 4 grams. The consistency of stools rapidly reverted to normal, starting after a 30 min long treatment period, in both of the groups. Group B (4 sachets) showed a more rapid improvement than group A (2 sachets). These findings demonstrate that the faster clinical response to Salovum was dose-dependent. The mean number of stools also rapidly decreased likewise over time in the two groups. When contacted at different time intervals during the rehabilitation period, none of the children showed a recurrence of diarrhea. This indicates the long-term effect of AF when fed to these children.
The response to AF agrees with previous studies in man and in animals (
). The randomization of the children resulted in an uneven distribution of age and gender. Thus, the patients in group B were almost twice as old as those in group A. The faster recovery in group B could consequently be a random occurrence due to this difference in age. However, the children in both the groups were equally well-nourished and they were frequently breastfed. Consequently, these factors could, therefore, not explain the difference between group A and group B in the response to the Salovum treatment.
One of the weaknesses of the study was that controls, i.e., children being treated using the standard regime only at the outpatient level or for the follow up, were not selected for the current study because we knew from our previous experience that the response is significant to Salovum using the different doses. Moreover, we had to restrict the follow-up to only 6 weeks because of the logistic reasons considering the burden on the staff and the increasing load of patients reporting to the Outpatients with other diseases as well. However, we would expect a longer duration of diarrhea-free period with the higher dose of Salovum post treatment. This was not addressed in the current study.
), the sample size was adequately selected due to a known level of outcome. The follow up was close and intensive, carried out by the pediatrician in charge and the appointed nursing staff that was present throughout the treatment time. The staff was trained beforehand in the collection of the information and observing the progress. Despite their training and supervision, they did not know which group was getting 2 or 4 sachets since only the pediatrician in charge knew the dispensation. The follow up was completed with daily contacts between the mothers and care-givers.
Moreover, the number of sick children in the area of the study is high during the year. It is of importance to counteract diarrhea as fast as possible in order to restore the body water and ion balance. The faster this clinical goal is achieved, the less is the risk for the diarrhea to develop further into a chronic or fatal diarrheal disease. This can also prevent the usage of any anti-diarrheal or antibiotics drugs, which can pose the danger of further damage to the gut.
The two and four-times increase in the dose of Salovum indicates the dose-response, suggesting that such diarrheal episodes can be treated as outpatients but, if made available, even can be used by the mothers at home in the absence of any side-effects (
). We have previously shown the reduction in diarrhea in young children occurring within a mean of 17 hours even when the dosage was less than the present one. The consistency of stools was also seen to revert to normal in 19 hours with the same dosage. So, high doses may provide a greater benefit to these patients in much less time.
The rapid, clinical action of Salovum noted in the presented diarrhea patients cannot be satisfactory scientifically explained. Thus, a detailed biological mechanism of action in vivo of the various AF peptides remains to be described. Experimental studies demonstrate that the AF peptide, AF-16, suppresses increased intracranial pressure in rats, and also decreases a high intratumoral pressure in rat mammary cancer (
). The registered suppression of the increased intracranial as well as intratumoral pressure is noted within minutes. Ongoing research has demonstrated an interaction in vivo between AF-16 and the flotillin-1 structure located to the inside of the cellular membrane. This interaction might directly influence the cellular membrane transport capacity for water and ions, which consequently should be reflected by an immediate decrease of the pressure. A similar mode of AF action in the affected intestine of the children with diseased diarrhea could partly explain the rapid mode of clinical action of Salovum in the diarrhea diseased patients.
Since no fecal bacteriological evaluations were performed on the patients in the present study, the diarrheal etiology in the different patients could, therefore, not be defined. It is most likely that the causative agents may be variable, ranging from viral to bacterial. This agrees with the fact that AF functions as a principal regulator of intestinal water and ion transport and performs its action irrespectively of the diarrhea-inducing mechanisms (
The protective and regulating influence of AF is presumably mediated via its capacity to normalize secretions and possibly also via its anti-inflammatory capacity as shown in several studies. The response to higher doses of Salovum did not cause any side-effects like vomiting or increase in secretory response showing worsening of diarrhea, but a prolonged, protective effect was notable in these children who returned to the same environment and remained diarrhea-free for 6 weeks in both of the groups. This suggests a prolonged resistance to diarrheal diseases initiated by Salovum.
Moreover, we had added Salovum to the oral rehydration salts routinely used in the management of acute diarrhea. None of the patients showed any aversion to either the salts or to the egg yolk mixed in it. A more longstanding and continuous stimulation of the endogenous AF system can be achieved by feeding the children with SPC-Flakes either as finely ground and mixed with milk or ordinary food, or as a muesli (
). Consequently, induction of increased AF production achieved via intake of SPC-Flakes over time might reduce the risk for infants and children in impoverished areas to the threat of repeated diarrheal diseases of varied etiology.
Conflict of interest
The authors have no conflicts of interest to declare.
Meetings where the information has previously been presented: None.
This study was supported by the Swedish Government under the LUA/ALF Agreement [Grant 71570 ], Sahlgrenska University Hospital [Grant 83030 , Lantmännen AS-Faktor AB, and Lantmännens Forskningsstiftelse [Grant no 2016S004 ].
The study was approved by the Ethics Committee of the Children's Hospital and Institute of Child Health, Lahore, Pakistan. An informed consent with Thumb impressions and contact details were also obtained before the patients were included for the study. The parents were free to withdraw from the study at their own will.
Uptake of the antisecretory factor peptide AF-16 in rat blood and cerebrospinal fluid and effects on elevated intracranial pressure.