Doctoral dissertation

Rotavirus Diarrhea Among Young Children Before Introduction of the Rotavirus Vaccine Program in Kenya

Tohtori
Diarrheal diseases are the second leading cause of childhood deaths globally. Rotavirus is a leading cause of severe dehydrating diarrhea which is particularly associated with morbidity and mortality among children under five years of age in low- and middle-income countries.

The rotavirus vaccine was introduced into Kenya’s public immunization program in July 2014, with a two-dose schedule at six and ten weeks of age. Estimating the burden of rotavirus-associated disease before vaccine introduction is essential for assessing the population-level impact of vaccination programs.

The aim of the dissertation of Richard Omore Onyando is to estimate the burden of diarrheal illness among children under five years of age before the introduction of rotavirus vaccine in Kenya and to provide baseline information on health care seeking, prevalence, hospitalizations, and potential complications of childhood diarrhea to help evaluate the impact of rotavirus vaccine program implementation in Kenya.

This dissertation consists of four original studies. In Study I, we conducted household interviews with caretakers of 1,043 children under five in a baseline cross-sectional survey (April–May 2007) and of more than 20,000 children on five subsequent surveys between May 2009 and December 2010 to assess healthcare- seeking patterns for childhood diarrhea (defined as 2 ≥ 3 loose stools in 24 hours).

In Study II, we conducted inpatient surveillance of children with acute gastroenteritis (AGE) (diarrhea and/or one or more episodes of unexplained vomiting occurring within seven days of admission) to estimate hospitalization and mortality rates due to all-cause and rotavirus acute gastroenteritis (RVAGE). Person-years of observation from an active Health and Demographic Surveillance System (HDSS) in western Kenya were used as denominators.

In Study III, we conducted hospital-based surveillance of children under five years with acute, nondysenteric moderate-to-severe diarrhea (MSD) to assess factors associated with rotavirus gastroenteritis and to describe illness severity. We defined non-dysenteric MSD as diarrhea with one or more of the following: sunken eyes, skin tenting, intravenous rehydration, or hospitalization, and acute to mean seeking care for the diarrhea episode within seven days of illness onset at a study sentinel health center located within the HDSS. Stool specimens from participants enrolled in Studies II and III were tested for rotavirus using an enzyme immunoassay. To describe the epidemiology and risk factors for intussusception-related mortality, we retrospectively reviewed medical chart data of patients under five years old diagnosed with intussusception in 12 Kenyan leading referral hospitals (Study IV).

Our results showed that the two-week population-based incidence proportion of any diarrhea during the study period ranged from 26% at baseline (2007) to 4– 11% during 2009–2010. A key finding of the surveys was that less than half of the children with diarrheal illness received care at a healthcare facility. Caretakers were actually less likely to seek health care outside the home for infants with diarrhea than for older children. Seeking care outside the home for childhood diarrhea was significantly more common for children who had sunken eyes during their diarrheal episode. Substantial proportion of children with diarrhea were given less food and drink than normally, even when vomiting accompanied their diarrheal episode. They were also not offered oral rehydration solution (ORS) at home.

Mothers with formal education, however, were more likely than those without formal education to provide their children with ORS at home and to take them to a health care facility. Furthermore, caretakers sought care from a healthcare facility when their child`s diarrheal illness became more severe— possibly as a consequence of giving no remedy at home. Infants 6–11 months had the highest population-based incidence rates for hospitalization and mortality due to AGE and RVAGE. Rotavirus-positive cases were younger (median age, 8 vs. 13 months), had more severe illness, and had to be hospitalized more frequently than those who were negative for rotavirus. Independent factors that were associated with rotavirus disease included being an infant and presenting with vomiting 3 or more times within 24 hours during the diarrhea episode. Two-thirds of intussusception cases treated from 2002 through 2013 were infants who presented with at least one of the following symptoms: vomiting, diarrhea, or blood in stool. The case-fatality proportion was 6.4%. Compared with patients who survived, patients who died were younger, more likely to seek care late after illness symptom onset, to report history of fever on admission or, to have undergone surgery.

In summary, the studies in this thesis demonstrate that diarrhea among young children presenting to health care facilities is a significant public health problem in Kenya. However, the cases attending health care facility are only the tip of an iceberg.

Our findings that suggest delay in seeking care for the child`s severe diarrheal illness are disconcerting. In addition, among children with severe disease symptoms and intussusception patients who died had sought care later after symptom onset than those who survived. Our data also confirmed that morbidity and mortality associated with AGE, RVAGE, and intussusception was most common among infants.

These findings supported the Kenyan Ministry of Health’s decision to introduce a rotavirus vaccination program in July 2014. They are also consistent with the WHO recommendation to administer rotavirus vaccines to children at six and ten weeks of age, before the peak of disease incidence in Kenya.

As a whole, the results of this thesis provide a comprehensive baseline data on occurrence, risk factors and complications of rotavirus diarrhea among young children in Kenya against which the population-level vaccine program impact can be evaluated in the future. Continuing surveillance efforts aimed at demonstrating the real-world impact and value of rotavirus vaccines need to take into consideration the observed trends in health care utilization.

The doctoral dissertation of Richard Omore Onyando Rotavirus Diarrhea Among Young Children Before Introduction of the Rotavirus Vaccine Program in Kenya will be publicly examined at Tampere University Faculty of Social Sciences on Friday 10 Jan at 12 o'clock in Arvo building auditorium F 114, Arvo Ylpön katu 34. The opponent is Dr. Roger I. Glass (Fogarty International Center, National Institutes of Health, U.S.A). Professor Pekka Nuorti will act as custos.
 

The dissertation is available at http://urn.fi/URN:ISBN:978-952-03-1365-4