PDF
Citation
Print
INTRODUCTION
The role of diarrhea in childhood death remains clinically significant. Diarrhea accounts for approximately 9% of deaths in children under 5 years of age, despite improved sanitation and nutrition as well as the introduction of oral rehydration therapy and rotavirus vaccination.12345 The success of these measures varies according to regional settings and infrastructures, especially in water, sanitation, and hygiene (WASH) services, which are still inadequate in some countries.14
Diarrheal disease in North Korea accounted for 13% of deaths among children aged 1–59 months and 0.2% of deaths in neonates aged 0–27 days in 2017.6 Substantial progress has been made considering the figures reported in 2000 (21% of deaths in children aged 1–59 months; 0.5% of deaths in neonates aged 0–27 days), however, there is room for improvement. In North Korea, diarrhea is mainly attributed to the lack of WASH services, whereas diarrhea-related mortality has been affected by long-standing food insecurity since the 1990s.78 Only 67% of the population utilized safely managed water supplies in 2017; the gap between urban and rural areas was 27% (urban population 77%; rural population 50%).9 The proportion of household populations in North Korea using an appropriate water treatment method (e.g., boiling and water filters) was only 16.5% in 2017. As many people are unavoidably using poorly managed wells exposed to industrial effluent and feces, the risk of waterborne diseases exists.1011
International communities and nongovernmental organizations (e.g., the Swiss Agency for Development and Cooperation and Concern Worldwide) have supported WASH programs in North Korea, and local efforts have led to progressive improvements in the quality of WASH services.1012 However, further development of plans to comprehensively reform the water supply and sewage systems has been hindered by the enormous cost required, deeming the issue a low priority.1314 Therefore, humanitarian aid and health authority efforts toward managing diarrheal diseases have focused simultaneously on other clinical and therapeutic aspects. Oral rehydration solutions, nutritional support, and medical supplies for treating children with diarrheal diseases administered through numerous projects from international communities, particularly the United Nations Children’s Fund, have been provided for decades.1516 Aid for developing medical infrastructure has also been provided along with individual supplies. For example, a large hospital for children was built in 2004 to manage diarrheal diseases and nutritional disorders (Pyongyang Okedongmu Children’s Hospital), and its therapeutic approach was strengthened by constructing facilities for manufacturing soybean milk next to the hospital.15 The nutritional support was helpful in the effort to escape the vicious circle originating from the bidirectional relationship between diarrhea and malnutrition.17 Reliable provision of medical supplies in addition to the nutrition supply was also reported to contribute to improved diarrhea treatment outcomes.
Humanitarian aid and cooperation in the field of health have aligned with the prevention and management guidelines for children with diarrheal diseases.518 However, information regarding the actual management of diarrheal diseases and the allocation of resources in North Korea is limited. Oral rehydration solution or therapy was administered to approximately three-quarters or more of children under 5 years with diarrhea in 2009 (74.0% received oral rehydration solution, 91.5% received oral rehydration therapy),1920 whereas 97.8% of children aged 6–59 months received regular vitamin A supplementation in 2012.1621 However, the credibility of the statistics cannot be determined owing to a lack of information; other than a few incomplete ideas, no specific clinical database for diarrheal diseases has been established in North Korea. Some information has been provided through media reports on recent conditions in North Korea (e.g., acute enteric epidemics), but the full details remain undisclosed.22
Analyzing North Korean medical journals can help understand the current situation concerning infant mortality due to diarrhea. Through journal analyses, researchers have employed an indirect approach to better understand various aspects of North Korean medicine, such as in the surgical or psychiatric fields.23242526 However, to the best of our knowledge, no comprehensive review has been conducted to identify studies on diarrheal diseases in children based on North Korean articles. A detailed review of published studies in North Korea may guide policymakers in developing healthcare initiatives in the country. The original treatment modalities utilized in isolated countries, such as the Galapagos, might provide clues to aid in effectively reducing diarrhea-related mortality in developing countries in addition to currently established treatments.27
In this study, an article analysis was conducted based on the following research questions: 1) how are diarrheal diseases in the pediatric population handled in research fields and 2) how has treatment been administered in North Korea? Clinical needs and concerns regarding treatment modalities are also discussed.
METHODS
An analysis of articles published in three North Korean medical journals, “Pediatrics, Obstetrics, and Gynecology,” “Internal Medicine,” and “Preventive Medicine,” from 2012 to 2019, was conducted considering the scope of the journal and data availability during the included period.28 Recent issues published from 2020 to 2023 were unavailable because of the coronavirus disease 2019 (COVID-19) pandemic and consequential border closures in North Korea. The journals were obtained from the printed database of the Information Center on North Korea (Seoul, Republic of Korea) by the Ministry of Unification, Republic of Korea (July to October 2021). All of the articles were published in Korean by “Medical Science Publishing House (Ŭihak-kwahakch'ulp'ansa; Pyongyang).” Only journals published in North Korea were selected as clinical settings inside the secluded country were inaccessible from external perspectives.
Systematic reviews or meta-analyses were not available for this study owing to the lack of references and peculiar characteristics of North Korean studies.2728 North Korea is widely known for its undisclosed clinical settings and figures, medical professionals from the outside world are seldom permitted access to ordinary medical circumstances. Relevant literature for a systematic review focusing on North Korean clinical settings is nearly impossible to search and collect from research databases or registers.
This absence of data has led researchers to use references published within the country. A thorough investigation of all articles published in North Korean journals helped overcome the data deficiency23242526; nevertheless, the abbreviated composition of the articles (one or two pages per article on average) hindered the rigorous analysis of the database. The omission of fundamental details (e.g., study population definitions, inclusion or exclusion criteria, and diagnostic tools) in articles also occasionally misguided researchers.
Therefore, despite possible bias, a narrative review was performed as a suboptimal tool to reflect clinical practice. One researcher, a medical doctor, initially reviewed the papers to determine whether the study results included diarrhea-related topics. Original articles and case reports were included; editorials, review articles, and invention reports were excluded. In the next phase, the papers were analyzed and sorted by three reviewers (a medical doctor and two experts on North Korean studies) according to the inclusion and exclusion criteria.
The inclusion criteria were as follows: 1) human studies and 2) a focus on the clinical features or epidemiology of patients with diarrhea. The exclusion criteria were as follows: 1) trials reporting only disease prevention without real-world patient cases and 2) studies that were not fully available in the database. Studies that included human and animal models were excluded from the analysis. Articles involving adult populations were excluded from the final screening phase. The age range in the pediatric population varied among studies but mainly included infants, toddlers, and preschoolers.29 Studies that included some proportion of school-aged children or adolescents and articles that did not provide a specific pediatric age range were included to avoid discounting each treatment modality.
RESULTS
Article distribution
A total of 5,211 publications (1,483 from “Pediatrics, Obstetrics, and Gynecology,” 2,075 from “Internal Medicine,” and 1,653 from “Preventive Medicine”) were initially identified through a database search from 96 issues (four issues published each year; three journals) between 2012 and 2019. The initial screening process yielded 53 articles on diarrhea; however, only 43 exclusively reported on pediatric populations (Fig. 1).
Among the 43 articles, 38 were published in “Pediatrics, Obstetrics, and Gynecology,” whereas the others were published in “Preventive Medicine.” Papers on diarrheal diseases published in “Internal Medicine” included adult populations and were therefore excluded. The distribution of each study during the investigation period is presented in Table 1. Among all papers published in the journal “Pediatrics, Obstetrics, and Gynecology,” the proportion of papers on diarrhea in children was 2.56%, whereas the proportion was 0.83% when all three journals were included.
Table 1
Distribution of research papers on diarrhea in children by publication year and journal
Among the 43 papers on diarrheal disease within the pediatric population, approximately three-quarters (33 of 43, 76.7%) were case-control studies. In contrast, the proportions of observational studies and case reports were 20.9% (nine of 43) and 2.3% (one of 43), respectively. The mean sample size was 243.1.
Types and etiology of diarrhea
Among the 43 papers, nine (20.9%) reported on children with infectious diarrhea, including three papers on viral (n = 4,287), four papers on bacterial (n = 2,519), and two papers on parasitic diarrhea (n = 361). One-fifth of the papers (eight of 43, 18.6%; n = 749) included diarrhea caused by indigestion or malabsorption. The remaining papers (26 of 43, 60.5%; n = 2,536) did not clarify the etiology (e.g., unclassified or multiple types of diarrhea).
Viral diarrhea
All articles on viral diarrhea reported a population with rotavirus infection, and a latex agglutination test was utilized for detection. A study published in 2014 reported seasonal fluctuations in diarrhea due to rotavirus. The highest detection rate for the rotavirus antigen test was observed during winter (December to February, 55.3%), whereas the lowest rate was detected during summer (June to August, 21.7%). The detection rates in spring (March to May) and fall (September to November) were 36.2% and 37.1%, respectively.
Viral diarrhea articles evaluated clinical features, including the degree of dehydration, frequency of defecation, type of stools, and other subjective symptoms (e.g., nausea, bloating, and agitation). Clinical symptoms, such as sunken eyes and lip dryness, were regarded as indicators of dehydration. The stool was categorized into four types: watery stool, watery stool with granules, stool with granules, and mucous stool.
Bacterial diarrhea
Half of the studies on bacterial diarrhea focused on children with Klebsiella pneumoniae. One paper published in 2012 reported seasonal fluctuations in bacterial diarrhea due to K. pneumoniae, the detection rate was highest during summer (9.2%), but the difference was not statistically significant. The detection rates in the other seasons were 8.5% in spring, 8.3% in fall, and 7.6% in winter. The other half of the papers on bacterial infections, including Escherichia coli (O111, O128), Shigella spp. (S. sonnei, S. flexneri), and Salmonella spp. (S. typhimurium, S. enteritidis, S. choleraesuis). The detection methods were not provided in detail.
Bacterial diarrhea articles assessed clinical characteristics, including frequency of defecation, type of stools, blood tests (e.g., total serum protein, complete blood count), and other subjective symptoms (e.g., weakness, anorexia, nausea, bloating, and agitation). Stool type categorization differed according to the study design but mainly included the following: mucous, mucous bloody, mucous-watery, and watery.
Parasitic diarrhea
Two studies focused on parasitic diarrhea caused by Cryptosporidium parvum and Giardia duodenalis. Fluorescent antibodies and polymerase chain reaction tests were used to detect C. parvum. A study published in 2017 reported seasonal fluctuations in parasitic diarrhea in 2013 due to C. parvum; however, the distribution of cases according to the detection time was provided instead of the detection rate among all patients with diarrhea. In children with diarrhea, 52.1% of cases caused by C. parvum were detected in summer (25 patients of 48), whereas the lowest proportion was observed in winter (2.1%, one patient of 48). The distribution of cases in the other seasons was 8.3% in spring (four patients of 48) and 37.5% in fall (18 patients of 48).
Parasitic diarrhea articles focused on clinical factors, including the frequency of defecation, type of stools, and other subjective symptoms (e.g., stomachache and bloating). Stool types included watery, mucous, and mucous-bloody.
Diarrhea due to indigestion or malabsorption
Stool acidity and fecal-reducing substances were used as markers for diagnosing and evaluating diarrhea caused by indigestion or malabsorption, including lactose intolerance. The following clinical features were considered: degree of dehydration, frequency of defecation, type of stools, blood tests (e.g., total serum protein and albumin level), and other subjective symptoms (e.g., nausea, vomiting, agitation, anorexia, and bloating).
Specific details regarding indicators for evaluating the degree of dehydration were provided in some of the papers compared with those reporting on other types of diarrhea. The papers reported symptom evaluation, including sunken eyes, sunken fontanel, weight loss, urine output, thirst, lip dryness, and skin dryness. Stool type categorization was based on the criteria utilized by each author and mainly included lienteric, watery-lienteric, and mucous-lienteric stools.
Treatment modalities for diarrhea in the pediatric population
Probiotics
Using probiotics for treating diarrhea in children was reported in 16% (seven of 43) of the papers, mainly in the studies with diarrhea due to indigestion (three of seven). Lactic acid bacteria and Bifidobacteria were the main focus, including Lactobacillus spp. (e.g., L. acidophilus, L. brevis, L. delbrueckii subsp lactis, L. fermentum, L. reuteri), Lactococcus sp. (e.g., L. lactis subsp lactis), and Bifidobacterium sp. (B. bifidum). Probiotics were often administered with milk, candy powder, or flour (e.g., beans, corn, and potatoes).
Studies on butyric and gluconic acids were also conducted to improve the clinical conditions of patients with diarrhea. These studies compared the effectiveness of each type of bacterium; however, some reported no significant differences.
Vitamin and mineral supplementation
Researchers utilized vitamin and mineral supplementation to bolster diarrhea treatments. Six of the 43 papers (14.0%) included vitamin supplementation; however, it was mostly provided to the control and experimental groups as basic care. One study published in 2012 evaluated the role of vitamin A deficiency in promoting recovery after diarrhea. The target of vitamin supplementation was not limited to a specific etiology of diarrheal diseases.
Zinc supplementation was discussed in only two studies (4.7%). In a 2013 study, researchers suggested zinc supplementation in combination with extracts from garden balsam for treating diarrhea (etiology not specified). In contrast, a 2018 study compared the effects of combination therapy on bacterial diarrhea (norfloxacin and zinc supplementation versus norfloxacin and extracts from deer antlers). The administration methods for zinc supplementation differed according to the study design, including “nano zinc” and tablets. Although “nano zinc” may refer to dietary zinc oxide nanoparticles, specific details on treatment modalities were not provided.
Rehydration
Details on using oral rehydration solutions (or intravenous fluid) were not included, and in some cases, rehydration therapies were not mentioned in the articles. Only 48.8% of the articles reporting on diarrhea (21 of 43) mentioned rehydration therapies, whereas 39.5% (17 of 43) evaluated the degree of dehydration with or without specific indicators such as urine output. The target of rehydration therapy was not limited to a specific etiology of diarrhea.
A few researchers have attempted to maximize the effect of rehydration solutions on diarrhea using two different approaches: adjusting the osmolarity of the solution or combining it with other herbs. One study published in 2018 evaluated the treatment outcomes of acute diarrhea in infants according to the osmolarity of the oral rehydration solution and concluded that 225 mOsm/L was the preferred option over other osmolarity conditions (245 mOsm/L, 235 mOsm/L, 215 mOsm/L, and 205 mOsm/L) based on clinical criteria (skin dryness, lip dryness, urinary frequency, defecation frequency, and serum sodium). Oral rehydration solution was administered in the following dosages: 75 mL/kg in mild cases and 100 mL/kg in moderate cases in 4 hours. Alternatively, studies published in 2016 and 2017 attempted to enhance the effect of oral rehydration solution by adding herbal extracts, such as yellow ginseng and ash trees, despite contrasting results.
Antibiotics
One-third of the articles on diarrhea in children (13 of 43; 30.2%) used antibiotics. However, antibiotics were used primarily in ancillary roles in treatment modalities or administered to the control groups to evaluate and compare the therapeutic effects of their novel approach.
Co-trimoxazole (trimethoprim and sulfamethoxazole) and metronidazole were frequently used, while fluoroquinolones (e.g., ciprofloxacin and levofloxacin), tetracyclines (e.g., oxytetracycline), and rifamycins (e.g., rifampicin) in control groups were also reported. A few examples of combination therapy were noted, including those with other medications (e.g., rifampicin and prednisolone) or North Korean Oriental medicinal ingredients (e.g., norfloxacin and extracts from deer antlers).
North Korean Oriental medicine
Several therapeutic trials for treating diarrhea using North Korean Oriental medicine (Koryo medicine) have been reported. More than half of the papers (24 out of 43; 55.8%) reporting on diarrhea in children included oriental approaches with or without the application of other therapies. The target of oriental medicine was not limited to the specific etiology of diarrheal diseases. Researchers have mainly used 1) extracts from herbs and animals, 2) minerals and water, and 3) manual therapies. A list of the approaches used in each study according to the type of diarrhea is presented in Table 2.
Table 2
North Korean Oriental medicine utilized for treatment of diarrhea in the child population
Many herbs and animals have been used to treat diarrhea in children. Extracts from acorn and yellow ginseng were used more frequently than other ingredients. Byproducts from the activity of bees (e.g., propolis) or aphids (e.g., Galla Rhois) were also included, as were extracts from deer antlers. Minerals were applied as part of the treatment; however, the major components and processing methods for these minerals (e.g., Kumkang-yak-dol and Sindae-alyak) were not reported. Ozonated water was administered orally to patients with diarrhea caused by rotavirus compared with patients in the control group who received oral rehydration and intravenous dextrose solutions.
Manual therapies utilized in alternative medicine were also identified. Moxibustion and cupping use were noted, while acupressure and acupuncture were also used to treat diarrhea. Most therapies were applied in combination with other types of herbal medicines, except for one study that only utilized acupuncture and moxibustion for managing patients with chronic diarrhea. However, studies using these approaches have not clarified the types of diarrhea being managed.
DISCUSSION
Through this review, we analyzed studies on childhood diarrheal diseases published between 2012 and 2019 in North Korea. North Korean children were diagnosed with infectious diarrhea (e.g., viral, bacterial, and parasitic) and diarrhea due to indigestion or malabsorption. However, accurate prevalence rates could not be determined from the journal analysis. Various modalities have been utilized to enhance the effectiveness of diarrhea treatment, from basic rehydration therapies to traditional Oriental medicine (i.e., Koryo medicine). The screening results before the analysis indicated that the research focus regarding diarrhea was primarily on children rather than adults, considering the proportion of each article among all included publications. The relatively high mortality rate due to diarrheal diseases in children might have increased the concern of clinical researchers in North Korea.
Although an organized approach was used in treating most patients, not every possible treatment was administered because of limited resources. Our study provides insights into determining priorities for supporting the efforts to reduce childhood deaths due to diarrheal disease in North Korea, along with developing appropriate WASH services. Providing support for rotavirus vaccination programs is one of the best options. Despite the unsatisfactory circumstances that some healthcare providers have concerning the lack of adequate rotavirus knowledge, a recent evaluation of the effectiveness of the attenuated human rotavirus vaccine by researchers in North Korea showed promise.30 The rotavirus vaccine is a cost-effective measure for preventing diarrhea-related deaths.3132 Appropriate assistance to expand routine vaccination programs, including vaccine administration or education sessions for healthcare providers, is needed.
Zinc supplementation can be an inexpensive and convenient option in North Korea. Administration of zinc (e.g., 20 mg per day, 10–14 days) is recommended in children with diarrheal disease to help reduce the duration and improve clinical symptoms.3334 However, no comparative preference for supplemental zinc was found. Supplying zinc tablets on a large scale, specifically low-dose tablets (e.g., 5 mg per day), can prevent additional resultant gastrointestinal symptoms such as vomiting in the pediatric population.35
Rehydration therapy is the most fundamental approach for preventing diarrheal mortality.3336 However, the interpretation of this approach was ambiguous and controversial because rehydration therapies (48.8%) and evaluation of the degree of dehydration (39.5%) were not mentioned in the research papers on diarrhea in children. Modern facilities for manufacturing oral rehydration solutions in North Korea constructed under humanitarian aid in the early 2000s are currently managed under the authority of the supreme leader Kim Jong-un.1537 Considering pre-existing reports that oral rehydration solution or therapy is administered to many children with diarrhea, it is reasonable to infer that the basic information of the treatment modalities was omitted from the descriptions provided in North Korean research papers.1920 Articles published in North Korea are known for their abbreviated form; only one to two pages on average are allotted for each paper in major journals.28 However, it is possible that the optimistic figures reported regarding rehydration therapy are far from reality. State-run manufacturing facilities have encountered multiple difficulties, including a lack of raw materials, electricity, and clean water, and some healthcare workers have been reported to supply rehydration solutions on their own because of inadequate supplies.38 Aside from the reliability of homemade solutions, the widespread reuse of disposable medical supplies such as vials or saline bags may also be a reason for concern regarding secondary infection in the patient population.39
Diverse therapeutic approaches were utilized to treat diarrheal disease with North Korean Oriental medicine. However, supplementary studies are required to demonstrate their efficacy and reliability to establish these approaches as priorities for support. Previous research findings partially support data concerning the ingredients utilized in the studies. Deer antler and insect gall (e.g., Galla rhois), both utilized in bacterial diarrhea cases, are suggested to have antibacterial effects according to in vitro studies and swine clinical trials.4041 Some researchers present the utility of acupuncture or moxibustion to relieve diarrheal symptoms.4243 Nevertheless, high-level evidence is needed for each ingredient or therapy to be clinically utilized in the human population.44
Further evaluation of the accessibility of each ingredient is required before it can be used in other developing countries. Certain materials utilized in the studies were not readily available in countries outside North Korea; some were only cultivated in particular regions (e.g., yellow ginseng). Other materials were not cost-effective for treating diarrhea compared with other currently used therapies (e.g., deer antlers).45
Although the situation during the COVID-19 pandemic is not precisely known, it is highly likely that it has deteriorated along with other conditions in the medical field. As the import of essential resources (e.g., raw materials, foods, and medications) from China was disrupted in the early stages of the pandemic owing to extensive border closures, fundamental conditions, including nutrition and healthcare services, were also aggravated. For instance, medication imports in 2020 ($17.2 million) plummeted compared with those from the previous year ($44.4 million),46 possibly leading to the debilitation of medical environments.
The priorities of the health authorities were also concentrated on COVID-19 control rather than other healthcare issues under limited resources.47 While the specific budget allocation by sector during the pandemic cannot be validated, some media reports suggest that diarrhea management resources were not adequately provided.22 Further investigation regarding the current situation and long-term implications for childhood health in North Korea is needed to develop an in-depth discussion to provide medical support.
A comparison with other countries that are making efforts to manage childhood diarrhea may also provide further insights into handling these problems in North Korea. Efficacious interventions and approaches have been attempted globally, including WASH programs, rotavirus vaccinations, and clinical management.48
The WASH interventions have been proven to significantly reduce the prevalence of diarrheal diseases under proper management (e.g., studies in Bangladesh, South Africa, and Ethiopia).495051 Moreover, rotavirus vaccinations have substantially reduced diarrhea-related hospitalizations and mortality (e.g., studies in Mexico and Botswana).5253 These preventive measures have sustainably improved overall health outcomes, along with various clinical management strategies for diarrheal diseases. Although these countries differ in their fundamental infrastructure and healthcare capacities, previous successful experiences can strengthen their potential implementation in North Korea. Additional research is required to analyze cost-effectiveness in each case and determine optimized settings in North Korea. A maximally integrated approach, rather than an individual perspective, must be achieved within the framework of limited resources.
This review analyzed studies on diarrheal diseases in North Korea, which account for a large proportion of childhood deaths. Despite the existence of established guidelines for treating childhood diarrhea, knowledge regarding the actual clinical approaches for diagnosis and treatment under limited resources in North Korea is limited. We provide insights to understand the types of diarrhea and unmet needs in clinical settings despite the possibility of bias owing to methodological limitations. A list of priorities may be helpful to healthcare workers and policymakers in further developing support plans.
However, the lack of detailed information about the study population in the studies might have weakened the integrity of the analysis. Some papers did not clarify the specific pathogens or causes of diarrheal disease, and there was relatively little focus on populations of children with diarrheal symptoms without infection (e.g., symptoms resulting from malabsorption or indigestion). Therefore, our findings may only provide a preliminary summary of recent clinical approaches for managing diarrheal diseases. Additional investigations into identifying and obtaining unavailable research papers published during the COVID-19 pandemic (2020–2022) may provide further clues for interpreting the situation under aggravated conditions.
Procedural restrictions, such as United Nations sanctions against North Korea, should also be considered when prioritizing support. Related expert groups may need to discuss additional prerequisites for humanitarian sanction exemptions.
The findings from an analysis of papers reporting on diarrhea in the pediatric population provide information on the current clinical approaches for treatment in North Korea. The rotavirus vaccine, supplemental zinc, and rehydration solutions should be prioritized while considering safety, cost-effectiveness, and procedural restrictions. Additional follow-up studies are required to obtain detailed information.
XML Download