Our study is one among a small number of studies addressing delays in diagnosis and treatment of childhood cancers in low- and middle-income countries (LMIC). We identified 5 earlier studies, 2 of which focused on leukemia, 1 on retinoblastoma and 2 on all childhood cancers
[11–14]. To our knowledge, our study is the first that focuses exclusively on diagnosis delays among children with BL, which is a physically evident disease and therefore easier to detect by untrained parents. In both Kenya and Uganda, we observed long delays from onset of symptoms to first treatment, with the median total delay about 12 weeks in both settings. In comparison, a recent meta-analysis that pooled data on time to diagnosis among Non-Hodgkin Lymphoma patients in HICs (n = 1081) reported a median total delay of 3.8 weeks
. Findings from the earlier studies addressing delays in diagnosis in LMIC were varied. Median total delays were 4.1 and 4.4 weeks for leukemia, 15 weeks for retinoblastoma, and 4.9 and 13.1 weeks for studies including all childhood cancers. Of note, Brown et al. reported results on delay in Nigeria stratified by diagnosis and found median delay among children with BL was 9.7 weeks, slightly shorter than present findings
In both of our study populations, guardian delay constituted the majority of the total delay—74% in Kenya and 65% in Uganda. Median health system delay was 2 weeks in Kenya and 2.6 weeks in Uganda, Length of health system delay at both sites was comparable to data from earlier studies on delays for other childhood cancers in LMIC: in Nicaragua (2 weeks) and South Africa (3 weeks), although less than delays observed in Nigeria (9 weeks)
[11, 13, 14]. In contrast, guardian delay in the present study was considerably longer than previous reports—9 weeks in Kenya and 4.6 weeks in Uganda as compared to 1 to 2 weeks in other LMIC settings studied
[11, 13, 14]. Overall, our findings differ from those previously reported, which have shown a tendency for guardian delay to be less than health system delay, both in LMIC and HIC
[11, 13, 14, 16].
The long guardian delay in our study may reflect guardians’ perceptions of illness, misinterpretation of early symptoms, poor access to health care facilities (distance and transportation availability and financial constraints) and competing household and work responsibilities. Although delays in diagnosis appear to be largely due to guardian delay in our study population, we also observed considerable variation in delay among respondents. That is, health system delay emerged as the main component of total delay for many—15% in Kenya and 42% in Uganda. Across both settings, guardians reported multiple care nodes and complex and indirect pathways of navigation. Prolonged health system delay in these cases and others may be partially explained by limited knowledge of BL among health service providers, insufficient clinical investigations or failure to refer patients to heath facilities with resources for further management. Another important consideration is the limitations of the guardian delay versus health system delay dichotomy. This construct establishes two separate time intervals to attempt to isolate and examine delay that may be explained by guardian-level factors separately from that which may be attributable to the health system. This framework relies on the false assumption that there is no interplay between these factors. That is, it implies that after a child reaches the first health facility, the care-seeking experience is essentially sheltered from guardian-level influences like region, cost and availability of transportation and health beliefs. The limitations of this construct become most apparent in the context of multiple visits to care facilities as many of the same factors influencing guardian delay may contribute to delays in pursuing follow up care. Additional studies would be necessary to disentangle the longitudinal contribution of these elements.
Few of the factors investigated were found to be associated with guardian delay or health system delay in Kenya and Uganda. Many of the guardian socio-demographic characteristics did not influence delays in either settings, including age, education, occupation and select indicators of socioeconomic status (housing, windows, home cooking apparatus, water source and animals in home). Past research that has examined the influence of education on diagnosis delay in childhood cancers has been inconsistent. Several studies in LMIC and HIC have shown shorter total delay
[16, 17] and guardian delay
[12, 18, 19] with increased levels of education, yet other studies—conducted in Nigeria and South Africa—have found education to have no significant effect
[11, 14]. With few respondents reporting education beyond primary school, it is possible our study population was too homogenous to discern any significant association.
In Kenya, we found guardian’s relationship to the child had no effect on delay. However, in Uganda, total delay was found to be greater among those who identified as primary caretaker as compared to those who did not. These findings may reflect the influence of several factors on primary caretakers and their access to care, including household and work obligations and the availability of social support. The benefit of social resources, from family and/or friends, in overcoming barriers to healthcare utilization has been well characterized throughout the literature
. In the present study, support largely came from other family members rather than the community, with nearly all guardians reporting shifting roles among families as a consequence of the child’s illness.
Interestingly, there was no association between select indicators of socioeconomic status and delay in either Kenya or Uganda. Structural factors including travel time and costs of transportation to the JTRH and UCI also did not emerge as independent predictors of delay in our analysis. Our results contradict previous studies in Kenya and Uganda, which have shown reduced access to and utilization of health services among lower socioeconomic groups, with distance to the facility and costs of care among the key barriers
[20–23]. These earlier findings are supported in our study, however, by guardians’ perceptions of the barriers to care. When asked what was most difficult about bringing the child to the hospital, financial issues were the leading concern, often related to costs of transportation and clinical care. Many of the guardians traveled long distances to reach JTRH and UCI and nearly all used public transportation. Travel time and transportation costs were particularly high in Uganda, where UCI serves a broader catchment area as the national cancer referral center; JTRH in contrast is one of several regional cancer referral centers in Kenya. In both of these settings, guardians reported multiple health encounters prior to JTRH and UCI, resulting in accumulating costs, of travel, user fees, diagnostic tests and treatment, none of which were assessed in the present study. Thus, it is conceivable that measured costs were too narrow in scope to observe any correlation. Future studies should explore the impact of these additional costs on delay, as well as indirect costs such as loss of daily income.
Our results related to guardians’ knowledge of cancer indicate low awareness of cancer among the general community. Interestingly, however, knowledge of cancer or specifically BL did not appear to influence delay in either setting. This suggests interventions aimed solely at increasing disease awareness may be insufficient for improving early diagnosis. Also evident from these findings is that guardians arrive at UCI and JTRH with a limited understanding of their child’s illness despite multiple encounters within the health care delivery system leading up to admission to the cancer center. This may partially reflect the fact that many children remained undiagnosed or were misdiagnosed at lower-level facilities; however, insufficient communication between health providers and guardians may also be a contributing factor.
Perceptions of cancer were largely similar among guardians in Kenya and Uganda. Few thought cancer was contagious or viewed the illness as a curse or a bewitchment. One exception was stigma, which was more common in Uganda than Kenya. Although past studies have shown stigma and fears of discrimination can be an important barriers to care, these sentiments were not associated with delay in the present study
. Overall, few guardians in Uganda and Kenya perceived cancer as curable. In Uganda, surprisingly, guardian delay was significantly greater among those who did. We believe this may be a spurious association, however, as few of these guardians (17%; 4 of 24) suspected their child’s illness was cancer before seeking care. In both settings, misconceptions related to the curability of BL have important implications for efforts to improve early diagnosis. Guardians who learn or suspect their child has cancer may be less likely to utilize health services if they perceive treatment will have little to no benefit
. Understanding that BL is a curable illness provides hope and reason to pursue care.
Earlier research has shown that initial presentation of symptoms can influence time to diagnosis for other malignancies, including retinoblastoma, brain tumors and leukemia
[12, 16, 17, 26]. In the present study, we found no difference in delay according to early symptoms or guardians’ interpretations of the symptoms. These findings may be attributable to the non-specific symptoms observed in early BL. This non-specific presentation, and BL’s relative rarity, underscores the inherent challenges of timely diagnosis of this disease. Symptoms common to many conditions can lead not only to varying perceptions of illness among guardians, but also frequent misdiagnosis in clinical settings. An example in malaria holoendemic areas where splenomegaly is common would be the misdiagnosis of an abdominal tumor located on the left side as opposed to the right side of the body.
Guardians in both settings experienced lengthy health-seeking itineraries, often consisting of several different types of health facilities. Guardians most commonly first sought care in Uganda at private clinics, and in Kenya, at dispensaries; about half visited other care providers. Notably, almost all guardians reported that they first sought western medicine and not care from traditional healers. It is possible however that use of alternative forms of care such as traditional medicine may be underreported due to perceived stigma. Although various levels of health facilities typically differ in their human resources and institutional capacities, there were no significant differences in delay according to the first point of care. Brown et al. reported similar results related to total delay, but found increased guardian delay at tertiary care centers when compared to lower-level facilities
. Many of the health encounters in our study resulted in sub-optimal care, including misdiagnoses and inappropriate treatment, particularly at lower-level facilities. We examined treatment practices across various levels of the health system however data were insufficient to identify any trends. Future studies should explore this relationship as any findings may yield valuable information for improving care delivery. Overall, our results suggest that interventions designed to address diagnosis delays should include outreach and continuing education for health professionals across multiple levels of the health system. Local providers must be able to recognize early signs of cancer and make appropriate referrals and adequately communicate the need for haste to the parents.
An earlier study on guardians’ perspectives of barriers to pediatric cancer care was conducted at UCI in 2007, three years prior to our study (K. Stiffler, University of Washington School of Public Health Masters thesis). A similar survey was administered to 32 guardians of children with cancer on arrival to UCI; 23 of the children were diagnosed with BL. Comparison of findings from the two studies yields interesting insight into possible changes in health-seeking behaviors among guardians in Uganda, and their experiences navigating the health-system for effective treatment.
Overall, the mean total delay, from onset of symptoms to arrival at UCI, remained largely similar from 2007 to 2010 at 18.5 and 20.4 weeks, respectively. In contrast, there was a shift in the main component of total delay, from health system delay in 2007 to guardian delay in 2010. The mean health system delay decreased from 69% of the total delay (12.9 weeks) in 2007 to 23% in 2010, whereas the mean guardian delay increased from 31% of the total delay (5.2 weeks) to 77%. This comparison is limited by several factors, including slight differences in study procedures and questionnaires, and missing 2010 data on guardian delay and health system delay, as discussed previously. With data only available for guardians with 3 or less health encounters prior to UCI, it is possible that 2010 estimates of health system delay represent a slight underestimation. Despite this limitation, the marked difference between these two estimates suggests that the time to UCI after guardians first seek care may be decreasing. One possible explanation may relate to differences in the study population, with guardians from 2010 representing a slightly broader catchment area. Mean travel time among this group was 5.8 hours as compared to 2.9 hours in 2007. This could reflect increasing country-wide awareness of cancer due to the collaboration between UCI and the Fred Hutchinson Cancer Center and the formation of The Uganda Program on Cancer and Infectious Disease that has been receiving a lot of media attention. Both studies identified transportation and financials costs as the most important barriers to seeking care.
Many of the factors investigated in the present study, including knowledge and attitudes toward cancer and structural barriers to care, contribute not only to late stage of presentation, but also refusal and abandonment of therapy, one of the leading causes of poor outcomes in resource-limited settings
. For example, in a recent study on BL in Nigeria where parents were required to pay for chemotherapy and laboratory diagnostics, only half of all children presenting to the hospital completed treatment due to financial constraints; 20% never initiated treatment and another 32% abandoned treatment due to costs
. Israëls et al. also reported similar findings from a study on abandonment among guardians of children with BL and Wilms tumor at a public hospital in Malawi, where treatment is provided free of charge
. Factors influencing abandonment included financial costs related to transportation, food and loss of income; household responsibilities; and perceptions related to the curability of cancer.
Our study has several limitations. The sample sizes in both Kenya and Uganda were relatively small. Secondly, all data were self-reported. Guardians were asked to report on several variables across multiple health encounters that took place over an extended period of time. Thus, recall bias is a concern. Perhaps most importantly, our findings represent only those guardians who successfully navigated the health system, received appropriate referrals and arrived at the cancer centers, UCI and JTRH, for treatment. Many other children with BL in both settings may have been less fortunate and remained undiagnosed or mismanaged at lower-level facilities. Community-based investigations of the health-seeking experiences would provide additional insight into the barriers to diagnosis and treatment, including factors that may have not been examined in the present tertiary care, hospital-based setting.
Using guardian delay and health system delay to analyze time intervals across the care-seeking experience also has several limitations. One source of bias stems from our methods of measuring guardian delay, which relied on questions of when symptoms were first recognized and when care was first sought. Assessing symptom recognition and interpretation presents many difficulties that have been well characterized throughout the literature
. Although this discussion is beyond the scope of this paper, it is important to note that our analysis relied on the flawed assumption that all guardians recognize and interpret symptoms in similar ways. A more comprehensive inquiry into guardians’ perceptions of symptoms would provide a more accurate and precise assessment of guardian delay. Lastly, many of the same factors influencing guardian delay can influence health system delay, particularly with multiple health encounters, as previously discussed.