A systematic review of human giardiasis in Bangladesh: public health perspective

Background: Giardiasis identified as a leading cause of gastrointestinal pathogen in young children worldwide, is also common in Bangladesh. There has been an emerging evidence of an association between giardiasis and child growth. This systematic review focuses only on Bangladeshi children. Prevalence of giardiasis with its adverse health effects and the advancement of diagnosis has been reviewed. Methods: A broad review of literature, electronic databases, and books within the time frame of 1970 and 2019 has been searched. Data published on giardiasis prevalence, outcomes (child growth, intestinal permeability, and diarrhea) and advances of diagnosis in Bangladesh has been searched. Results: Both assemblages A and B genotypes of Giardia lamblia are responsible for human giardiasis in Bangladesh. Recent studies on Bangladeshi children suggested Giardia species infections has an adverse impact on poor child growth which have further characterized associations with altered gut epithelial barrier dysfunction, as well as diarrhea. Indeed emerging evidence indicates the key consequence of Giardia colonization is nutrient malabsorption. Conclusions: In Bangladesh giardiasis remains a major public health concern, especially in children age <5 years but is considered as a neglected disease. In order to reduce the burden of giardiasis in developing countries such as Bangladesh, more focus is require to include this disease in public health policies.

Biological Science (DUJBS), Bangladesh Journal of Zoology (BJZ) and Bangladesh Medical Research Council (BMRC) and others has been searched. This review identified research studies related to Giardia infection and its adverse health effects across Bangladeshi population using keywords such as "Giardiasis", "Giardia infection", "Human", "Adverse effects/disorder", "Bangladesh".
In this review we excluded articles that did not had proper information. And the articles were also omitted that had only information related to experimental method, molecular and biochemical analysis of Giardia. In fact, papers were also removed from the consideration without full text access after searching in other databases. The last date searched was November 30th, 2019.

Results
Description of the studies identified: We found 187 titles on the initial search, of which only 17 met the inclusion criteria and were finally included for this systematic review. Figure 1 shows the way to get the articles used in this review according to PRISMA. Thus, in this review we included possible health risk of giardiasis from 17 articles.

Epidemiology:
Giardia infection occurs worldwide (17) with the highest burden of giardiasis borne by people living in developing countries, particularly the tropics and subtropics, where hygiene and sanitation are inadequate like Bangladesh. Giardiasis was estimated to be as high as 20 to 40% in resource-limited settings with the highest infection rate among children under the age of 5 (18). Diarrhea associated with intestinal protozoal parasites such as Giardia, Entamoeba and Cryptosporidium has been one of the main reasons of child mortality in developing countries in sub-Saharan Africa and South Asia, including Bangladesh (19,20).
In low and middle-income countries (LMIC) such as Bangladesh, the exact burden of giardiasis is difficult to quantify as the reports can vary by geographic region, study design, sample size, incubation, severity of symptoms, and the sensitivity of the diagnostic method.
In a large case-control study conducted on 2534 patients in Bangladesh, association between infection with G. lamblia genotypes assemblage A and assemblage B were tested ,where significant odds ratio for diarrhea was observed for assemblage A infections whereas assemblage B infection was associated with asymptomatic Giardia infection (21). In another study performed in an urban slum of Dhaka, Bangladesh, shown 31.1% of children had at least one episode of Giardia lamblia diarrheal infection in first 2 years of age (22).

Giardiasis And Poor Child Growth:
Associations between Giardia infection and child growth impairments varied by study, population and location, but children in Bangladesh are consistently associated with poor child growth with Giardia infection burdens (Table 1).
Giardia had a considerable negative correlation with linear growth in a cohort study of malnutrition and enteric disease (MAL-ED), which lasted for the first 2 years of life up to 5 years in some cases.
Giardia infection was associated with smaller reductions in the length-for-age z score (LAZ) in quantity instead of prevalence using the exposure criterion (32). In another case-control study on Bangladeshi children showed that Giardia infection was significantly related to undernourished cases after age, sex, and diarrhea were modified and further adjusted to sociodemographic factors (33). Similarly, from a prospective birth cohort study in Dhaka, 7% of children were Giardia positive (stool specimen) with a decreased LAZ score in the first 6 months of life as an early life risk factor (34). Moreover, infection with Giardia before 6 months of age was associated with a decrease in LAZ − 0.29 (95 percent CI, − 0.64 to 0.07) and a decrease in weight-for-age z score (WAZ) at 24 months of age − 0.29 (95 percent CI, − 0.53 to − 0.05) indicating a stunted growth rate (35). In addition, evidence of elevated Giardia-specific IgM titre (GSIgM) was found in a longitudinal study of 298 rural Bangladeshi infants associated with poor WAZ and weight-for-height z score (WHZ) (P = 0·015 and 0·039 respectively) (36). This findings suggest that infection with Giardia could be a potential obstacle to poor child growth up to 2 years of life and a crucial window of childhood vulnerability that is rarely recorded in a focused manner. Giardiasis And Intestinal Permeability: Infection with Giardia has been correlated with altered human bowel architecture and experimental models (28,41,42). In this regard, Bartelt et al. identified Giardia as a "stunting" pathogen (42) resulting in malabsorption of glucose, sodium and water in the body and decreased production of disaccharides (43)(44)(45)(46)(47)(48). In MAL-ED study, Giardia infection was associated with high level of lactulose: Additionally an observational study of Bangladeshi infants of an urban area indicated giardiasis was associated with the intestinal barrier disruption (38). Furthermore, another prospective longitudinal study confirmed that giardiasis was significantly associated with concentrations of fecal myeloperoxidase (MPO) and alpha-1-anti-trypsin (AAT) in children under the age of 2 and was also significantly associated with score of environmental enteric dysfunction (EED) (37 reported 11% pre-school children were infected with Giardia lamblia which one is second highest after Shigella flexneri (11.6%) in diarrheal stool (55). Table 2 shows the prevalence rate of giardiasis in diarrheal stool by different test methods.  showed that childhood growth retardation has been associated with giardiasis in developing countries (65)(66)(67)(68)(69). Recent data from Bangladeshi children found similar results indicating that infection with Giardia could be a potential barrier to children's development (32)(33)(34)40). The prospective MAL-ED birth-cohort study give us a special opportunity to explore the relationship among giardiasis and child growth (35). Diarrheal diseases is a crucial problem in public health that particularly affects children in Bangladesh (71). The bidirectional correlation between malnutrition and diarrheal mortality has been known for decades (72,73). Enteric infections such as Giardia spp. cause a significant proportion of global malnutrition. (73). Although more studies are needed to determine the actual health effects of giardiasis. Recently, an increased number of Giardia spp. has been identified in Bangladesh, especially in children.
This systematic review has few limitations including the number of articles observed. As we followed a

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