A wide geographic variation in the incidence of intussusception among and within countries makes determining a true prevalence of the disease difficult. It is estimated that incidence in the United States is approximately 1 case per 2000 live births. In Great Britain, incidence varies from 1.6 to 4 cases per 1000 live births. Overall, the male-to-female ratio is approximately 3:1. With advancing age, gender difference becomes marked; in patients older than 4 years, the male-to-female ratio is 8:1.
Two thirds of children with intussusception are younger than 1 year; most commonly, intussusception occurs in infants aged 5–10 months. Intussusception is the most common cause of intestinal obstruction in patients aged 5 months to 3 years, and mortality varies with the geographic location.1 Data on the incidence of intussusception in developing countries and especially in the African countries are limited mostly due to under- or nonreporting, but overall the case fatality appears to be high in developing countries.2–4
ETIOLOGY AND PATHOGENESIS
The pathogenesis of idiopathic intussusception is not well established. It is believed to be secondary to an imbalance in the longitudinal forces along the intestinal wall. In entero-enteral intussusception, this imbalance can be caused by a mass acting as a lead point or by a disorganized pattern of peristalsis (eg, an ileus in the postoperative period). Some of the implicated lead points include Meckel diverticulum5 and enlarged mesenteric lymph nodes. However, of particular interest in this case report is electrolyte disturbances and viruses as possible etiologies. A seasonal variation in the incidence of intussusception that corresponds to the peaks in frequency of gastroenteritis (spring and summer) and respiratory illnesses (midwinter) has been described. Lappalainen et al6 have studied prospectively the role of viral infections in the pathogenesis of intussusception. They concluded that the simultaneous presence of human herpesvirus-6 and adenovirus infections appeared to correlate with risk of intussusception.
In 1999, an association was found between the administration of a rotavirus vaccine (RotaShield) and the development of intussusception.7 An estimated 1 excess case of intussusception occurred for every 10,000 children vaccinated. RotaShield was removed from the market in the United States <1 year after it was introduced and was not used in other countries. These patients were younger than usual for idiopathic intussusception and were more likely to require operative reduction. It was hypothesized that the vaccine caused reactive lymphoid hyperplasia, which acted as a lead point.
Despite the setback with the RotaShield rotavirus vaccine, development of new vaccines continued, and this resulted in licensure of 2 new oral vaccines. These vaccines are the 2-dose monovalent (RV1) Rotarix (GlaxoSmithKline Biologicals, Rixensart, Belgium) and the 3-dose pentavalent (RV5) RotaTeq (Merck & Co. Inc., West Point, PA).
No increased risk of intussusception was detected with either RV1 or RV5 in 2 randomized controlled trials, each of which included approximately 60,000–70,000 infants (30,000–35,000 received rotavirus vaccine) and designed to detect a risk similar to that observed with RotaShield.8,9
Efficacy was higher in middle and high-income countries (85%–98%) compared with low resource countries in Africa and Asia (39%–77%).10,11 Subsequently, World Health Organization prequalified these 2 new rotavirus vaccines and recommended they be introduced in the national immunization program in all countries.12 However, as rotavirus vaccines are introduced into immunization programs, monitoring their safety should be considered because of possible differences in factors such as varying ages at immunization in different countries and the characteristics of infants receiving the vaccine in routine use compared with the clinical trials conducted under experimental conditions.13
Subsequently, self-controlled case series and case-control studies were designed to investigate the potential association between RV1 and intussusception after routine immunization of infants in Mexico and Brazil. An increased risk of intussusception 1–7 days after the first dose of RV1 was identified among infants in Mexico. Studies using infants in Brazil showed no significant risk after the first dose, but an increased risk by a factor of 1.9–2.6 was observed 1–7 days after the second dose.14
In Australia, increased cases were seen compared with the expected cases of intussusception for both RV1 and RV5 among children 1–3 months of age. With RV1, the relative risk was 3.5 during 1–7 days after the first dose and 1.5 during 1–21 days after the first dose. The corresponding figures for RV5 were 5.3 and 3.5.15 New rotavirus vaccines (Rotarix and RotaTeq) have been associated with only a small increased risk of intussusception (1:20,000 to 1:100,000).
South Africa started rolling out rotavirus vaccine into National Immunization Program in September 2008, and other African countries are beginning to make this lifesaving vaccine available to children.16,17
Although intussusception can occur naturally and is a very rare condition, it is important for doctors in Africa to investigate in detail including confirming the vaccination status, document and report/publish data on cases of intussusception identified at the hospital facilities.
Diagnosis of Intussusception, Ventersdorp District Hospital, South Africa
An 8-month-old baby girl was brought by her mother to the emergency department and presented with the following history:
- Three days of vomiting, diarrhea and general malaise. No mention of bloody stools on questioning thereof.
- Clinically, the child was found to be pyrexial, 10% dehydrated clinically and no abdominal distension noted. Her temperature was 38°C. She was admitted having been assessed as acute gastroenteritis with severe dehydration. She was then rehydrated with intravenous fluids and started on ceftriaxone empirically.
- Blood tests revealed a markedly elevated WCC of 35 × 109 with a neutrophilia, monocytemia and a C-reactive protein of 72, all in keeping with a possible bacterial infection. Hematological investigations revealed a normocytic anemia.
The child had a normal birth; all immunizations were up to date as expected of an 8-month child according to the South Africa Expanded Programme on Immunization guidelines. Notably, the rotavirus vaccination, first dose of Rotarix vaccine was given on September 14, 2012, and second dose had been administered at 10 weeks of age on October 12, 2012. The child presented to the hospital on April 29, 2013, 6 months and 2 weeks after the last dose of rotavirus vaccination.
After 24 hours, the child had not improved having 3 loose bloody stools, lethargy and spiking temperatures. A fluid bolus was given with slight improvement. Later in the day, a stool sample was collected for microscopy culture and sensitivity.
On day 2 of admission, the child was still passing loose blood-stained stools. Hb dropped to 9.2 g/dL. The mother mentioned that the child had developed cough. Clinically, the child was not in respiratory distress. Empiric antibiotics were continued.
A radiography was done on day 3 after the child was examined and found to have a distended abdomen. This was initially attributed to a paralytic ileus as a result of the electrolyte disturbances resulting from the profuse diarrhea.
On day 4, the child’s condition was unsatisfactory and was not showing any improvement. The results of the stool microscopy culture and sensitivity were available, and only normal flora isolated with increased (3+) erythrocytes. Re-examination of the radiography revealed dilated small bowel loops.
The nonimproving clinical picture, despite antibiotics for what was seemingly acute bacterial diarrhea, coupled with the special investigations raised the suspicion of another diagnosis. The medical officer then suspected intussusception requiring surgery.
The surgical consultant that performs weekly ward rounds at the district hospital visited and on examining the child, agreed with the provisional diagnosis of intussusception. The patient was duly transferred to a tertiary hospital and an ultrasound done which confirmed intussusception.
A pneumatic reduction was attempted and free air was noted. The surgeons then proceeded to do a laparotomy that revealed an ileocolic intussusception and volvulus (Waugh’s syndrome; Fig. 1). Intraoperatively, multiple perforations of the bowel were found. The intussusception partially was reduced, and volvulus untwisted. The bowel was deemed nonviable, and a right hemicolectomy with primary anastamosis was then done. The child recovered after the operation and was discharged 4 days later.
Important Points to Note for African Doctors
Doctors may suspect intussusception as a differential diagnosis for any child presenting with bloody stools, despite raised septic markers and spiking fevers.
Early collection of stool samples could confirm suspicion of dysentery and as in this case, exclude it, creating a stronger case for diagnosis of intussusception.
Need to Increase Awareness of Intussusception in Africa
The medical officer who managed this case at the emergency department of Ventersdorp District Hospital, South Africa, and who suspected intussusception gained some valuable knowledge on the diagnosis and management of intussusception because he attended Seventh African Rotavirus Symposium on November 8, 2012, a 1-day pre-conference symposium which included a session on intussusception organised during the First International African Vaccinology Conference held in Cape Town, November 8 to 11, 2012.
Countries and partners should consider organizing awareness courses/workshops on intussusception targeting African doctors as the rotavirus vaccines are being introduced into national immunizations program.
Even in countries where rotavirus vaccine has been introduced in the Expanded Programme on Immunization, not all cases of intussusception will be associated with vaccination and hence the need to ensure doctors collect and record all the clinical, laboratory results, age, vaccination history of diagnosis and management of every case of intussusception.
The authors extend gratitude to the family of the child described in this case report for sharing a copy of vaccination card and other useful information.
2. Steele AD, Patel M, Cunliffe NA, et al. Workshop on intussusception in African countries–meeting report. Vaccine. 2012;30(suppl 1):A185–A189
3. Tate JE, Steele AD, Bine JE, et al. Research priorities regarding rotavirus vaccine and intussusception: a meeting summary. Vaccine. 2012;30S:A179–A184
4. Jiang J, Jiang B, Parashar U, et al. Childhood intussusception: a literature review. PLOS One. 2013;8
5. Milbrandt K, Sigalet D. Intussusception associated with a Meckel’s diverticulum and a duplication cyst. J Pediatr Surg. 2008;43:e21–3 –e
6. Lappalainen S, Ylitalo S, Arola A, et al. Simultaneous presence of human herpesvirus 6 and adenovirus infections in intestinal intussusception of young children. Acta Paediatr. 2012;101:663–670
7. Zanardi LR, Haber P, Mootrey GT, et al. Intussusception among recipients of rotavirus vaccine: reports to the vaccine adverse event reporting system. Pediatrics. 2001;107:E97
8. Ruiz-Palacios GM, Pérez-Schael I, Velázquez FR, et al.Human Rotavirus Vaccine Study Group. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med. 2006;354:11–22
9. Vesikari T, Matson DO, Dennehy P, et al.Rotavirus Efficacy and Safety Trial (REST) Study Team. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N Engl J Med. 2006;354:23–33
10. Madhi SA, Cunliffe NA, Steele D, et al. Effect of human rotavirus vaccine on severe diarrhea in African infants. N Engl J Med. 2010;362:289–298
11. Armah GE, Sow SO, Breiman RF, et al. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial. Lancet. 2010;376:606–614
12. . WHO position paper – Rotavirus vaccine: Weekly Epidemiological Record (WER); February 2013;88:49–64
14. Patel MM, López-Collada VR, Bulhões MM, et al. Intussusception risk and health benefits of rotavirus vaccination in Mexico and Brazil. N Engl J Med. 2011;364:2283–2292
15. Buttery JP, Danchin MH, Lee KJ, et al.PAEDS/APSU Study Group. Intussusception following rotavirus vaccine administration: post-marketing surveillance in the National Immunization Program in Australia. Vaccine. 2011;29:3061–3066
16. Seheri LM, Page NA, Mawela MP, et al. Rotavirus vaccination within the South African Expanded Programme on Immunisation. Vaccine. 2012;30(suppl 3):C14–C20
17. Msimang VM, Page N, Groome MJ, et al. Impact of rotavirus vaccine on childhood diarrheal hospitalization following introduction into the South African Public Immunization Program. Pediatr Infect Dis J. 2013;32:1359–1364