Pediatric Infectious Disease Journal:
Intussusception Incidence Rates in 9 Zambian Hospitals, 2007–2011: Prerotavirus Vaccine Introduction
Mpabalwani, Evans M. MB ChB, MSc, MMed*; Chitambala, Pearson Diploma Clinical Medicine†; Chibumbya, Julia N. BSc‡; Matapo, Belem BA§; Mutambo, Helen MB ChB, MSc§¶; Mwenda, Jason M. PhD§¶; Babaniyi, Olusegun MB BS, MPH, MSc§¶; Munkonge, Lupando MD, FRCSI‖
From the *University Teaching Hospital, Department of Paediatrics & Child Health; †University Teaching Hospital, Department of Surgery, Paediatric Surgical Unit; ‡University Teaching Hospital, Virology Laboratory, Lusaka, Zambia; §World Health Organisation, Regional Office for Africa, Zambia; ¶World Health Organisation, Regional Office for Africa, Brazzaville, Republic of Congo; and ‖School of Medicine, Department of Surgery, Paediatric Surgical Unit, Lusaka, Zambia
Accepted for publication June 19, 2013.
The authors have no conflicts of interest to declare.
Address for correspondence: Evans M. Mpabalwani, MB ChB, MSc, MMed, Department of Paediatrics & Child Health, University Teaching Hospital, PO BOX 50001, Lusaka, Zambia. E-mail: firstname.lastname@example.org.
Background: Intussusception, a rare adverse event associated with rotavirus vaccines in some settings, is a common cause of intestinal obstruction in infants and toddlers globally with a peak age of 4–6 months. This age group may overlap with the extended age of administering rotavirus vaccine.
Methods: A retrospective (January 2007 to June 2009) and prospective (July 2009 to June 2012) survey was conducted in 9 Zambian hospitals. Children between 0 and 24 months who were operated on for intestinal obstruction/intussusception were identified in theatre log books. In the latter part of the survey, patients were recruited prospectively. Demographic, clinical and surgical data from hospital files were collected for each patient.
Results: One-hundred and five children were identified to have undergone surgery for intussusceptions. Many were boys 57.6% (57/99). Of those with complete data, intussusception was common in infants 86.9% (86/99) and many children (68.0%) were between 3 and 8 months of age with a peak age of 5–6 months. Lusaka had the highest number of children with intussusception with an estimated annual incidence rate of 12/100,000 in children <2 years of age. The overall case fatality rate was very high 33.7% (31/92).
Conclusion: Intussusception was common in infants with a peak age of 5–6 months, and of particular concern is the group of 2–4 months the age of rotavirus vaccination. The estimated incidence rate of 12/100,000 is an underestimate as many cases may not present for care. The high case fatality rate of 33.7% is due to both delayed presentation and diagnosis in hospital.
Rotavirus is the most common cause of dehydrating diarrhea in infants and accounts for nearly 430,000 deaths annually1 with over 90% of these deaths occurring in the developing world.2–4 In Zambia, sentinel hospital-based rotavirus surveillance started in mid 2006, and rotavirus diarrhea accounts for 35% in the <5-year-old children admitted for acute gastroenteritis.5–7 Two oral, live-attenuated rotavirus vaccines, Rotarix and RotaTeq are prequalified by the World Health Organization (WHO) and are considered safe and effective in preventing severe dehydrating rotavirus diarrhea.3 In June 2009, the WHO Strategic Advisory Group of Experts on Immunization recommended the introduction of rotavirus vaccine in developing countries where the vaccine is most needed.8 It is anticipated that within about 1–2 years rotavirus vaccines will be readily available in most national immunization programs in sub-Saharan Africa apart from South Africa, which already introduced rotavirus vaccine, Rotarix, in 2009. In January 2012, the Zambian Ministry of Health with the Centers for Infectious Diseases in Zambia rolled out rotavirus vaccine in Lusaka as a pilot project.
An earlier licensed rotavirus vaccine, Rotashield, Wyeth Lederle Vaccines, that was only used in the United States was withdrawn because some recipients developed intussusception, a rare adverse event.9–14 Intussusception is a cause of intestinal obstruction in infants and toddlers with a peak incidence among children 4–6 months of age.15 This age group may overlap with the extended age of administering the vaccine. WHO recommends that rotavirus vaccine should be introduced into national immunization programs with the first dose given between 6 and 15 weeks.2 The maximum age for administering the last dose of either rotavirus vaccine should be 32 weeks,16 although WHO recently relaxed its age recommendations for rotavirus vaccine.17 Therefore, determining the baseline data on intussusception in children is essential before rotavirus vaccine is introduced in the national immunization program. Further, establishment of a postmarketing national surveillance system to monitor adverse events like intussusception is recommended.18
This retrospective and prospective study seeks to evaluate the background of intussusception in 9 Zambian hospitals before the rotavirus vaccine is introduced. This study will form a platform for continuous active surveillance of intussusception in children aged <2 years in hospitals before and after the introduction of rotavirus vaccine in Zambia.
PATIENTS AND METHODS
Nine study sites were selected based on their capacity to do emergency pediatric surgery, 7 urban hospitals and 2 rural hospitals (Fig. 1). Zambia is sparsely populated with a population density of about 17 persons per square kilometer.
Data Collection and Intussusception Patient Identification
A retrospective survey was conducted in 9 Zambian Hospitals from January 2007 to June 2009. Children between 0 and 24 months operated on with a diagnosis of intestinal obstruction or intussusception were identified in theatre log books and medical files traced in wards/registry. From July 2009 to December 2011, all children presenting with intestinal obstruction with a diagnosis of intussusception were recruited prospectively into the study. Demographic, clinical and surgical data from hospital files were collected using a standard questionnaire. Data were analyzed using Epi info version 6.
Calculation of Intussusception Incidence Rates
To calculate intussusception incidence rates, the population of children <2 years was used for the particular district where the selected hospital is located as the denominator and the number of cases of intussusception as the numerator per 100,000. Projected populations of children below the age 0–2 years for every district or town were obtained from the 2010 Zambia census19 (Table 1).
There were 105 children identified with intussusception in the 9 selected hospitals (Table 1), 32 (35.1%) were identified retrospectively and 63 (64.9%) were identified prospectively (Table 2). The majority (67/105, 63.8%) were from Lusaka (Table 1). Of those with complete data, there were more boys with intussusception than girls (57/99, 57.0%). Intussusception was common in infants 86.5% (83/96) and many children (70.8%) were between 3 and 8 months of age with a peak age of 5–6 months (Table 3). There was no seasonality in distribution of intussusception (Table 2).
Of the 105 children identified with intussusception, 91 had information on diagnostic method. Of these 91 children, 50.5% (46/91) had plain abdominal radiographs with 41.8% (38/91) had exploratory laporatomy (Table 4). Abdominal ultrasound was rarely used as a diagnostic tool (7.7%). Most patients 56.3% (36/64) presented to hospital after 4 days of the onset of symptoms (Table 3). Almost all children (98/101, 97.0%) had surgical intervention for intussusception (Table 4) most likely due to late presentation. The case fatality rate (CFR) was very high 33.7% (31/92), (Table 4). The annualized intussusception rates ranged from 1.0 to 15.1 per 100,000 at Choma and Livingstone General Hospitals, respectively, although the absolute numbers were relatively small (Table 1). However, the estimated annual intussusception incidence rate of 12 per 100,000 (67/111,612 over 5 years) in Lusaka is probably an underestimate (Table 1).
This baseline survey of intussusception rates in Zambia shows that intussusception is common in children below the age of 1 year (86.4% of recorded cases). This proportion of cases among infants is slightly higher than that in an earlier study of intussusception in Zambia during the early 1980s, which found that 61.2% occurred in infants.20 However, this finding is consistent with the findings from other regions of the world such as in Thailand where 86% of intussusception in children <2 years of age occurs in infants.21 In South Africa, many children (89%) with intussusception were <2 years.22
Intussusception was most common in infants between 3 and 8 months (70.8%) with a peak at 5–6 months (36.5%). If rotavirus vaccine is administered on time at the recommended ages of 6 and 10 weeks (for Rotarix vaccine) and 6, 10 and 14 weeks (for RotaTeq vaccine), then children will be vaccinated when the risk of intussusception is low. However, children who present for vaccinations late will be vaccinated when the background risk of intussusception is high. This age group critically overlaps with the recommended age for administering rotavirus vaccine rotavirus vaccine.18 There are often delayed vaccinations in infants in sub-Saharan Africa and especially so in rural areas.23 Perhaps, the age restrictions for rotavirus vaccine if strictly followed might improve the vaccinations of infants at the recommended age.
There is no seasonality in the distribution of intussusception cases seen in this study in Zambia. Infants and toddlers with intussusception were evenly distributed throughout the year over the 5-year period. In Thailand, there is a trend of increased intussusception rates during winter season.20 Studies from the temperate climates show that intussusception incidence does not coincide with the increased incidence rates in rotavirus infections in winter.15 In Zambia, rotavirus is seen throughout the year with a slight peak during the cool dry season.5–7 As found elsewhere, the survey shows a higher proportion of boys to girls of 1.4:1.
The overall CFR (33.7%) is very high in Zambian children compared with South Africa (2%) as all the 9 sites in the latter were specialist units.22 In Zambia, there is only 1 pediatric specialist unit situated at the teaching hospital in Lusaka. This high CFR is most likely due to late presentation to hospital and also delayed diagnosis of intussusception in hospitals. A diagnosis of intussusception in infants who present with bloody diarrhea may be delayed because these infants are considered to have dysentery and are managed as such in accordance with the WHO Integrated Management of Childhood Illnesses guidelines adopted by Zambia. Peripheral health centers strictly follow these guidelines and only when the condition worsens such infants are referred to hospitals. Organizing transport to take the children to hospital is time intensive as ambulance services are nonexistent and further increases the time to treatment. The situation is particularly grave in the rural health centers. Once a child arrives in hospital, there may be further delay in referral of suspected intussusception. Thus, by the time the infant is presented to surgeons, the patient is critically ill and the outcome of surgery is often unfavorable. Among those with complete data, almost all the patients diagnosed with intussusception underwent surgery (97.0%, 98/101) often due to late presentation to hospital. A major limitation of this survey is that the rate of intussusception is likely an underestimate as many children with this condition may die before they even reach the hospital. Of those who manage to reach the hospital, some will die before they are attended to by surgeons. In developed countries, mortality due to intussusception is rare.15
The annualized incidence rates of intussusception over 5 years ranges from 15.2 per 100,000 in Livingstone to 1.0 and 5.1 per 100,000 in smaller district hospitals. The relatively high incidence rate of intussusception (15.2 per 100,000) at Livingstone General Hospital may be an overestimate because this hospital serves as a referral centre for nearby districts so the population denominator for Livingstone District underestimates the catchment population for this hospital. The incidence rate (12.0 per 100,000) at the University Teaching Hospital, Lusaka, and the low rates in other district hospitals, ranging from 1.0 to 5.2 per 100,000, most likely reflect the differences in expertize and diagnostic facilities or differences in treatment seeking behavior and not necessarily a true difference in incidence. That is, children with intussusception in Lusaka presenting to the University Teaching Hospital may be more likely to be diagnosed as such compared with those presenting in other hospitals in the country. Alternatively, children with intussusception may be more likely to present for care in Lusaka than in some of the more rural districts. Thus, hospitals such as the Mine Hospitals in Chililabombwe and Chingola that have the expertize and facilities may have low incidence of intussusception because children with intussusception in the district do not seek care or are not referred from peripheral health centers.
There is paucity of published studies reporting the incidence rates of intussusception in infants and toddlers in Africa as most studies have been done in all ages or children <15 years.14 The estimated baseline incidence rate of intussusception in children <2 years in Lusaka is 12 per 100,000 children, which is really an underestimation. This is much lower than that reported in South Africa with the incidence of 32 per 100,000 in children <2 years.22 This rate is much lower than those cited in developed countries such as United Kingdom, The Netherlands and Australia, where the incidence rate range from about 66 to 120 per 100,00015 and lower in poor resource countries such as Venezuela, 24 per 100,00015 and Thailand 47.8 per 100,000.21 The incidence rates of intussusception reported in the developed countries are much higher than those in poor resource countries. This observation may be due to better health facilities and high levels of expertize in developed countries as almost all infants and young children with intussusception are investigated and that they also present earlier for medical attention. Therefore, our reported incidence rate of 12 per 100,000 in Lusaka is certainly an underestimate as not all infants and young children with intussusception are investigated and documented.
Our study has several limitations. First, in the retrospective part of the study, some files were not traced resulting in incomplete data on sex, age, diagnostic methods and outcomes for some cases. Second, we identified cases at hospitals that had the capacity to do emergency pediatric surgery. We missed cases among children who died in the community without presenting for care or who presented to other facilities and were not referred on to 1 of the study hospitals. Thus, the true incidence of intussusception in infants and young children is higher than that reported in our study.
Intussusception naturally occurs among infants and young children in Zambia and is most common in infants with a peak age of 5–6 months. The high CFR of 33.7% is due to both delayed presentation and delayed diagnosis in hospital. Delayed diagnosis was partly because of the similar symptoms and signs of intussusception in initial stages to dysentery, a common condition in Zambia. The incidence rate of intussusception in children <2 years in Lusaka, Zambia is estimated at 12 per 100,000. Active surveillance of intussusception in infants and young children is important for understanding trends in intussusception and should continue in these 9 participating hospitals in the baseline survey. This is particularly important as systems of surveillance for intussusception will be in place before rotavirus vaccine introduction in the national immunization program. Further, continued active surveillance for intussusception postrotavirus vaccine introduction will be crucial to monitor postmarketing surveillance of rotavirus vaccine safety.
We thank WHO/AFRO for funding this survey and the Ministry of Health, Zambia for allowing us to conduct the survey in the 9 hospitals. We further thank Prof. Mari Kirsten of Steve Biko Academic Hospital, Pretoria, Republic of South Africa for providing us with the questionnaire and her invaluable advice during the conduct of study and write up of the article.
1. Tate JE, Burton AH, Boschi-Pinto C, et al.WHO-coordinated Global Rotavirus Surveillance Network. 2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12:136–141
2. World Health Organization. . Rotavirus vaccines. Wkly Epidemiol Rec. 2007;32:285–295
3. World Health Organization. . Rotavirus vaccines: an update. Wkly Epidemiol Rec. 2009;84:533–540
4. Parashar UD, Hummelman EG, Bresee JS, et al. Global illness and deaths caused by rotavirus disease in children. Emerg Infect Dis. 2003;9:565–572
5. Mpabalwani EM.. Acute viral gastroenteritis in under 5 year old children at the University Teaching Hospital, Lusaka, Zambia. 1994 MSc Dissertation University of Zambia Library;
6. Mpabalwani M, Oshitani H, Kasolo F, et al. Rotavirus gastro-enteritis in hospitalized children with acute diarrhoea in Zambia. Ann Trop Paediatr. 1995;15:39–43
7. Mpabalwani EM, Namwaka J, Monze M, et al. Rotavirus disease burden in children hospitalized with acute gastroenteritis at the University Teaching Hospital, Lusaka, Zambia [paper in preparation, September 2012].
8. World Health Organisation. . Meeting of the immunisation Strategic Advisory Group of Experts, April 2009—conclusions and recommendations, rotavirus vaccinations. Wkly Epidemiol Record. 2009;84:213–236 No. 23
9. Murphy TV, Gargiullo PM, Massoudi MS, et al.Rotavirus Intussusception Investigation Team. Intussusception among infants given an oral rotavirus vaccine. N Engl J Med. 2001;344:564–572
10. Murphy TV, Smith PJ, Gargiullo PM, et al. The first rotavirus vaccine and intussusception: epidemiological studies and policy decisions. J Infect Dis. 2003;187:1309–1313
11. Murphy BR, Morens DM, Simonsen L, et al. Reappraisal of the association of intussusception with the licensed live rotavirus vaccine challenges initial conclusions. J Infect Dis. 2003;187:1301–1308
12. Bines JE. Rotavirus vaccines and intussusception risk. Curr Opin Gastroenterol. 2005;21:20–25
13. 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
14. 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
15. Vaccines and Biologicals, Acute Intussusception in Infants and Children: Incidence, Clinical Presentation and Management; a Global Perspective. October 2002 WHO/V&B/02.19
16. Patel MM, Clark AD, Glass RI, et al. Broadening the age restriction for initiating rotavirus vaccination in regions with high rotavirus mortality: benefits of mortality reduction versus risk of fatal intussusception. Vaccine. 2009;27:2916–2922
17. World Health Organisation. . Global advisory committee on vaccine safety, December 2011. Wkly Epidemiol Rec. 2012;87:53–60
18. Post-Marketing surveillance of rotavirus vaccine safety. March 2009 WHO/V&B/09.01
19. Central Statistical Office. Census of Population and Housing. 2010 Republic of Zambia
20. Munkonge L. Experience in the management of intussusception in Zambian children. Med J Zambia. 1983;17:56–58
21. Chowalit K, Pawinee D, Tanit S, et al. Incidence of intussusception among children 0–5 years of age in Thailand, 2001–2006. Vaccine. 2009;275:116–119
22. Moore WS, Kirsten M, Muller WE, et al. Retrospective surveillance of intussusception in South Africa, 1998–2003. J Infect Dis. 2010;202(suppl 1):S156–S161
23. Clark A, Sanderson C. Timing of children’s vaccinations in 45 low-income and middle-income countries: an analysis of survey data. Lancet. 2009;373:1543–1549
intussusception; age group; 0–2 years; incidence rates; mortality; Zambia
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