Burden of Helicobacter pylori Infections and Associated Risk Factors among Women of Child Bearing Age in Addis Ababa, Ethiopia.
1.1. Background. Maternal mortality remains a major challenge to health systems worldwide and improving maternal health has been on the global health agenda for many years . Ethiopia has one of the highest rates of maternal mortality in Africa . H. pylori is an inflammatory gastric bacterial infection especially prevalent in developing countries. It is the most common bacterial infection worldwide, infecting almost half of people in developed countries and 80% of people in developing countries . Study conducted in Ethiopia showed that there are gaps on screening and treatment of infectious diseases including H. pylori that could contribute to high maternal morbidity . H. pylori infection has a role in the pathogenesis of various pregnancy related disorders through different mechanisms, mainly focused on iron deficiency anemia, thrombocytopenia, fetal malformations and fetal growth restriction . Chronic infection with H. pylori in pregnant women may also cause hyperemesis gravidarum (HG). This particular complication affects 0.3 to 2.0% of all pregnancies. Previous studies showed that HG has a strong correlation with H. pylori infection [5, 6].
Epidemiological studies suggested that anemia presumably due to iron deficiency is correlated to H. pylori infection. It is related to a high level risk of low birth weight, prematurity, and perinatal mortality. It is associated with anemia caused by iron deficiency regardless of the presence or absence of peptic ulcer disease. H. pylori is a cause of gastrointestinal blood loss, reduction in iron absorption, and increase of iron absorption by the bacteria [7, 8].
Moderate to severe maternal anemia has been associated with an increased risk of poor reproductive outcomes, including low birth weight and preterm birth deliveries . Early detection and treatment of multiple causes of severe anemia may reduce the risk of prenatal and maternal mortality .
The burden of H. pylori infection among various adults and pediatrics groups in Ethiopia is available and the burden could vary in the range of 80-93%. However, none of them address disease burden among women of child bearing ages . Diagnosis of H. pylori infection includes invasive techniques (requiring endoscopy) such as rapid Urease test, culture, and histology, and noninvasive methods such as serology, urea breath test (UBT), and stool antigen test. Invasive methods due to ethical issues and UBT because of the use of radioactive materials are prohibited in pregnancy [9, 11]. Serologic testing is the most common noninvasive diagnostic method for H. pylori and is relatively inexpensive and convenient; H. pylori tested by stool antigen test (HPSA) which is an enzymatic immunoassay to detect bacterial antigen of actual ongoing infection in stool is a reliable noninvasive marker in the primary diagnosis and in the monitoring of posttreatment outcome [9, 11]. Maternal health is complex and it requires different studies to identify the problem in each level of maternity health services. Hence this study aimed to determine the burden of H. pylori infection and associated factors among women of childbearing ages in the study area.
2.1. Study Setting and Context. Facility based cross-sectional study design was conducted among women of childbearing ages from April to October 2015. The study was conducted in Kolfe Keranio subcity, Woreda 9 Health Center, Addis Ababa, Ethiopia. The health centers were delivering service for about 150-200 out patients per day. On average 40-50 pregnant women visited the antenatal care clinics on daily bases. The health facility was well established and trained with different professional staff. The laboratory section was also fairly well equipped with laboratory equipment.
2.2. Study Population. Three hundred thirty-two women of child bearing age, who were attended antenatal care clinics and outpatient services in the health centers, were used as study populations.
2.3. Inclusion and Exclusion Criteria. All volunteer child bearing ages of pregnant and nonpregnant (16-45 years) women were included. However, women on triple therapy for H. pylori infection in the past two weeks of data collection period and presentation with severe medical conditions that necessitated urgent care were excluded from the study.
2.4. Sample Size and Sampling Procedures. The sample size was determined using single population proportion formula, considering the assumption that prevalence of H. pylori infection was taken as 24.1% previous study conducted in Nigeria . By considering 95% confidence interval (CI) and 5% of marginal level, the total sample size was calculated 332. We factored a 10% nonresponse rate in the sample size calculation. Simple random sampling was used to select the study participants. Each day, before the provision of health education, the names of every pregnant woman attending the antenatal clinic were taken. Fifty percent of the women were then randomly selected until the required sample size was attained. The probability sampling was employed to avoid selection bias.
2.5. Data Collection and Laboratory Procedure. A convenience sample of participants was recruited during the study period. For nonpregnant study participants the most common reasons for presentation themselves to outpatients' clinic were generalized medical healthcare seeking and in the same time, for pregnant women study participants the most common reasons for their presentation to the antenatal care clinic in the health center were for their prenatal and antennal care follow-up during pregnancy. Using a standard questionnaire, interviews with adult participants were conducted and information was collected on sociodemographic data and some clinical and behavioral variables.
Stool (fecal) Specimen Collection and Laboratory procedure: H. pylori infection was examined by using H. pylori stool antigen test kits (CTK Biotech HpSA kit, San Diego, CA 92121 Inc., USA). A random stool (fecal) specimen in a clean, dry receptacle was collected. Then the stool collection device with the specimen's ID number (patient ID sticker) was labeled. The stool collection device was opened by unscrewing the top and used the collection stick to randomly pierce in 2-5 different sites, twisting the collection stick into the fecal specimens to help collection if necessary. All inner grooves of the collection stick were filled with fecal specimen. However, excess fecal specimen on the outside of grooves was scraped off. The collection stick and tighten securely to close the stool collection device was replace. According to the manufacturer leaflet provided with the H. pylori test kits the relative sensitivity, relative specificity, and overall agreement were 96.7%, 93.8%, and 94.9%, respectively. Its analytical sensitivity was 100% positive detection rate at 1ng/mL of pylori lysate antigen in fecal specimens. All reagents were ready to use as supplied. Unopened test devices were properly stored at 2-30[degrees]C. It was ensured that the test device is brought to room temperature before opening, when stored at 28[degrees]C. The test device was stabled through the expiration date printed on the sealed pouch. The kits were not stored in the freezer or exposed to temperatures above 30[degrees]C. Lastly the stool collection device vigorously was shacked and ready for H. pylori test. An H. pylori stool antigen (HPSA) test was performed according to the manufacturer's recommendation. The tests were done with fresh stool samples. The results were evaluated within 10 minutes and tests with any change of color of the test-line were interpreted as positive.
Venous blood samples were collected following standard operating procedures (SOP) by well-trained laboratory personnel and were analyzed using cell dyne methods (Hemocount 30 [TS] hematology analyzer machine, Germany) to determine the hemoglobin level of study subjects and then hemoglobin value <12mg/dlfor nonpregnant and <11.0 mg/dl for pregnant women was considered as anemic according to hematology analyzer machine user manual. The manufacturer supplied controls were run every morning to ensure that the analyzer was operating within 2.0 standard deviations. The analyzer automatically sampled blood, processed, analyzed, and printed out the hemoglobin concentration levels.
Intestinal parasites identification was done by direct smear microscopy and formol-ether stool concentration technique. The stool samples were processing based on standard operation procedures described in Monica Cheesbrough .
2.6. Data Management and Quality Assurances. Before data collection, adequate training was given for data collectors and supervisors. Data collectors were instructed to check the completeness of each data before submission. Quality of data collection process and all laboratory procedures were supervised and monitored by the principal investigator.
2.7. Statistical Analysis. The collected data were checked for completeness and consistency and summarized using Microsoft office Excel. The data were coded and analyzed using SPSS version 19.0 (SPSS Inc. Chicago, USA) software. Descriptive statistics was employed for the analysis of demographic data. Association between the burden H. pylori infection and risk factors was assessed by Chi-square (X2) tests. We used odds ratios as a measure of association, with a 95% confidence interval. Variables with p-values < 0.2 at bivariable analysis and these with biological plausibility with respect to H. pylori infection were put into backward stepwise multivariable logistic regression to determine predictors for H. pylori infection in study subjects. P-value less than 0.05 was taken as statistically significant.
3.1. Study Subjects Characteristics. From the total 332 study participants that were involved in this study, 195 (58.7%) were pregnant and the remaining were nonpregnant women. The mean ([+ or -]SD) age of the respondents was 27.3 [+ or -] 4.7 years. Majority (82.5%) of the study subjects were married. Sixty-two (18.7%) of study subjects were illiterate. Most (70.2%) of childbearing women lived with a family number of four or more. Among the pregnant women, 44.6% and 28.7% were become pregnant for the first and second time respectively. Sixty percent and 31.7% pregnant women were within a gestational period of 1-12 weeks and 13-24 weeks, respectively. One hundred ninety (57.2%) of study participants had gastrointestinal illness. From the total of pregnant women, 74.4% had history of HG. In this study, stool parasitological investigation showed that 71 (21.4%) of study participants had different intestinal parasites. Regarding the risk factors, 6/332 (1.8%), 1/332 (0.3%), and 2/332 (0.6%) of women had an experience habit of drinking alcohol, cigarette smoking, and Khat chewing, respectively. Majority (81.3%) of them had an experience of drinking tea and coffee. Almost all (99.4%) of them were used tap water for drinking purpose and all of them were wash their hands before meals and after toile. Study participants showed that 71 (21.3%) of them had different intestinal parasites, 190 (57.2%) of them had history of gastrointestinal illness, 61 (18.4%) were anemic, and 145 (74.5%) were pregnant women with hyperemesis gravidarum [Table 1].
3.2. H. pylori Infections and Risk Factors. The overall burden of H. pylori infection among study subjects was 29% (96/332). About 36.0% of women in the age group of 31-35 years were had the highest burden of H. pylori infection. Around 43.2% pregnant women with 25-40 weeks gestational age have the highest burden of H. pylori infection compared to women within 13-24 weeks, which accounts 29.6%. The burden of H. pylori was lowest among women without children, 9/62 (14.5%) compared to women with three or more children; it accounts 9/21 (42.8%). A high increment of H. pylori infection was observed among women who had more household members. In this study, another important point showed that 44/61 (72.1%) of the study subjects were H. pylori infected and they were anemic [Table 2].
There was no statistically significance association between H. pylori infection and sociodemographic characteristics (age group, marital status, educational background, occupational status, and number of people in the household), and some expected behavioral and clinical risk factors like habits of drinking alcohol, cigarette smoking, Khat chewing, drinking tea and coffee, water source for drinking purpose, gestational period (week), gravidity (number of pregnancy), parity (number of children), and presence of intestinal parasites, whereas categorical Chi-square ([X.sup.2]) analysis showed that there was statistically significant association between H. pylori infection and pregnancy status ([X.sup.2]= 68.61, P=0.001), history of hyperemesis gravidarum in pregnant women ([X.sup.2] = 5.259, P=0.001), history of gastrointestinal illness ([X.sup.2] = 7.3235, p=0.007), and anemia status ([X.sup.2] = 68.61, P=0.001) of the study subjects [Table 2].
In this study the overall burden of H. pylori infection among study subjects was 29%. Burden of H. pylori infection among pregnant and nonpregnant women is 21.9% and 33.8%, respectively [Figure 1].
Results of multiple logistic regression analysis showed that pregnant mothers were 1.8 times more likely had H. pylori infection than nonpregnant mothers [AOR: 1.825, 95% CI=1.105-3.014, P=0.020]. The pregnant women who had history of hyperemesis gravidarum were seven times more likely had H. pylori infection than pregnant mothers without hyperemesis gravidarum [AOR=7.0281, 95% C.I=2.47-19.99, P=0.001]. Women who had gastrointestinal illness were 1 8 times more likely had H. pylori infection than who did not infected, even though there was no statistically significant H. pylori infection [AOR=1.86, 95% C.I= (0.953.667, P=0.060]. Another important point in this study is that also women who had low hemoglobin value were more likely had H. pylori infection than who had normal hemoglobin value (AOR=0.177, 95% CI=0.083-0.379, p=0.003)[Table 3].
In this study burden of H. pylori infection among pregnant women is lower than study reported 45.2% in Uganda and 52.4% in Belgium, Brussels [14,15]. However, this study finding is higher than studies conducted in France and Zanzibar that reported a prevalence of 21.5% and 17.5%, respectively [16,17]. The variation might be due to the difference in study settings, study population, and the laboratory method. In the study of Uganda and Belgium, Brussels, serological antibody test was used as compared to the current study. In the current study burden of H. pylori infection among pregnant women was similar to study reported 33.3% in US-Mexico and 24.1% in Nigeria [12,18].
In the current study, H. pylori infection among in the age group of 31-35 years was higher (36.8%) compared to in the age group of 21-25 years (21.4%). This might be due to H. pylori acquired during young age but it is asymptomatic, which lead to develop gastritis, peptic ulcers, and gastric carcinoma, usually during late adulthood [11,16].
The results of this study also showed that H. pylori infection was significantly high in the pregnant population with hyperemesis gravidarum accounting 29.6%, and this finding agrees with study conducted in Jeddah, Saudi Arabia, However, in case of Saudi Arabia there was a case control study with hyperemesis gravidarum and without hyperemesis gravidarum . But this study showed higher result than the study done in Izmir, Turkey, which showed that women who were H. pylori infected with hyperemesis gravidarum were 22.2% . The possible explanation for this result is that an association of H. pylori and hyperemesis gravidarum could be that an increased accumulation of fluid and a displacement of intracellular and extracellular volume occur as a result of increase in steroid hormones, and this condition results in a change of pH which could lead to the manifestation of a latent H. pylori infection in the gastrointestinal tract. The increased level of steroid hormones and human chorionic gonadotropins (HCG) during pregnancy also leads to changes in PH and motility of GI tract; this change favors activities of H. pylori infection .
In this study, 34.7% of H. pylori infected study participant women had history of gastrointestinal illness. This finding is relatively lower than study done in Chile, which reported 68.6% of study participant women had H. pylori infection among complaining dyspepsia . This indicates that one of the major consequences of H. pylori infection is its effect on acid production in the stomach. The bacteria affect the stomach cells that control stomach acid secretion. This can lead to overproduction of hydrochloric acid, paving the way for ulceration, then the acid producing cells themselves are affected, and less acid is secreted, causing low stomach acid. The consequence of low stomach acid is low B12, since it is difficult to assimilate the nutrient from animal protein if you do not have adequate stomach acid, leading to the fact that gastritis or stomach inflammation always accompanies infection [23, 24].
In these study findings, high prevalence of H. pylori infection was seen in anemic (72.1%) study women and H. pylori infection has been found to be associated with anemia. Our findings are similar to other studies in Baghdad , Jeddah, Saudi Arabia , Zanzibar , and India that showed that women who had been infected with H. pylori, indicating that they had high prevalence of anemia [17, 24]. The probable finding of this results could be due to some possible mechanism by which H. pylori affects iron metabolism by decreased absorption resulting from chronic gastritis , decreased gastric juice ascorbic acid concentration, increased hepcidin production associated with H. pylori gastritis, uptake of iron by H. pylori for growth, and decreased availability of iron by sequestration of iron in lactoferrin in the gastric mucosa and bacterium host competition for dietary iron supply . Another explanation most commonly offered for this relationship could be also based upon the development of H. pylori associated chronic gastritis with resultant achlorhydria and reduced ascorbic acid secretion leading to reduced intestinal iron absorption. Besides an association between anemia  and H. pylori includes occult blood loss from erosive gastritis  and sequestration and utilization of iron by the organism .
In this study another point observed is that pregnant women were significantly associated with H. pylori infection. These findings agree with that of Cardaropoli and Ehab reports [4,26]. This probably proposed that pregnant women are among the most vulnerable groups for H. pylori infection and a reduction of gastric acid production during early pregnancy as a result of increased accumulation of woman's body fluid, steroid hormone changes, and immunologic tolerance which could lead to the activation of latent H. pylori infection, which can exacerbate dyspepsia, nausea, and vomiting symptoms, because of underlying undiagnosed peptic ulcer disease, which in turn may affect maternal gastric absorption. Mild to moderate dyspepsia is commonly associated with nausea and vomiting and complicates about 50% of all pregnancies and it diminishes women's life quality and social functions during early pregnancy . However, in most women, these symptoms resolve by fluid and vitamin supplementation as well as dietary modification.
In this study H. pylori infection was still a problem among women child bearing age in study area. H. pylori infection was statistically associated with pregnancy status, low hemoglobin value, and presence of hyperemesis gravidarum in pregnant women. As H. pylori infection can lead to serious gastrointestinal problem throughout the individual's life, we would like to emphasize how important it is for H. pylori screening and eradication treatment to be conducted in the country. Therefore clinician and other responsible bodies should give a special attention for women who have been infected with H. pylori; however further large scale case control studies are warranted among study participants to understand between H. pylori infection and related risk factors.
Abbreviations HG: Hyperemesis gravidarum HC: Health center HP: Helicobacter pylori HPSA: Helicobacter pylori stool antigen test HCG: Human chorionic gonadotropins IDA: Iron deficiency anemia IQC: Internal Quality Control SMLS: School of Medical Laboratory Sciences SOP: Standard operational procedures WHO: World Health Organization.
The data used to support the mendings of this study cannot be shared in a publicly available data repository system, because there is no such a data repository system in the country. However, the data are available from the authors upon request.
The study was approved by Institutional Review Board (IRB) of Addis Ababa University, School of Medical Laboratory Science. In addition, official letter permission was obtained from the study site. Moreover, permission was obtained from respective health facilities.
Written consent was obtained from all study subjects for those who could write and read; for the illiterate ones they are verbally informed by data collector, and then informed consent was obtained. The authors kept the privacy and confidentiality of the study participants throughout the study process.
Conflicts of Interest
The authors declare that they have no conflicts of interest.
Kumera Terfa Kitila conceived and designed the study protocol, collected data, performed analysis, and interpreted data. Kassu Desta Tullu, Lemi Mosisa Sori, and Daniel Melese Desalegn critically reviewed and made progressive suggestions from the design to final write up of the result. All of the authors participated in data collection, analysis, and interpretation and critically evaluated and approved the manuscript.
The authors would like to acknowledge Addis Ababa University, school of Medical Laboratory Sciences for creating and facilitating this research opportunity. We express our heartfelt thanks to study participants for their willingness and being involved in this study. Lastly, the authors also acknowledge staff members of the health facilities that helped us in data collection, preparation and laboratory examination activities.
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Kumera Terfa Kitila [ID], (1,2) Lemi Mosisa Sori, (3) Daniel Melese Desalegn [ID], (1) and Kassu Desta Tullu (2)
(1) Ethiopia Public Health Institute (EPHI), Addis Ababa, Ethiopia
(2) Addis Ababa University, College of Health Sciences, Department of Medical Laboratory Sciences, Addis Ababa, Ethiopia
(3) City Government of Addis Ababa Technical and Vocational Education Training Agency, Addis Ababa, Ethiopia
Correspondence should be addressed to Kumera Terfa Kitila; firstname.lastname@example.org
Received 20 August 2018; Revised 17 October 2018; Accepted 31 October 2018; Published 12 November 2018
Academic Editor: Piotr Dziegiel
Caption: Figure 1: Burden of H. pylori infection among women of child bearing ages in a Woreda 9 HC from April to October 2015, Addis Ababa, Ethiopia.
Table 1: sociodemographic characteristics and associated risk factors among women of childbearing ages participated in the study in Addis Ababa, Ethiopia, April to October 2015 (n=332). Variables Frequency, Percentage N (%) Age group 16-20 42 12.7 21-25 123 37.0 26-30 94 28.3 31-35 38 11.4 36-40 35 10.6 Level of education Illiterate 62 18.7 Primary school 119 35.8 Secondary school 73 22.0 College/university 78 23.5 Marital status Single 51 15.5 Married 274 82.5 Divorced/Widowed 7 2 Occupational status Government 39 11.7 NGO 19 5.7 Private 128 38.6 House wife 129 38.9 House maid 17 5.1 Numbers of people in house hold Less than or equal to three 40 12.0 Four 59 17.8 Greater than four 233 70.2 Numbers of gravidity First pregnancy 87 26.2 Second pregnancy 56 16.9 Three 29 8.7 Greater or equal to four 23 6.9 Gestational period 1-12 weeks 117 35.2 13-24 weeks 62 18.7 Greater than 24 weeks 16 4.8 Number of child (parity) No child 62 31.7 One child 57 29.3 Two children 55 28.3 Three and above children 21 10.7 Habit of alcoholism Yes 6 1.8 No 326 98.2 Habit of smoking Yes 1 0.3 No 331 99.7 Chewing Khathabits Yes 2 0.6 No 330 99.4 Water used for drinking purpose Pipe water 330 99.4 Tanker water 2 0.6 washing hands before meals and after toilets used Yes 332 100.0 Consumption of tea and coffee Yes 270 81.3 No 62 18.7 History of Hyperemesis gravidarum Yes 145 74.5 No 50 25.6 History of gastrointestinal illness Yes 190 57.2 No 142 42.8 HPSA result Positive 96 29 Negative 236 71 Presence of intestinal parasite Parasite Seen 71 21.4 Parasite not Seen 261 78.6 Anemic status Anemic 61 18.4 Not anemic 271 81.6 NGO: nongovernment organization; HPSA: H. pylori stool antigen test. Table 2: Univariate analysis showing association of H. pylori infection with some associated risk factors among study participated in Woreda 9 HC, Addis Ababa, Ethiopia, April to October 2015 (n=332). Variables HPSA positive [chisquare] P-value N n (%) Age group 16-20 42 8 (19.1) 21-25 119 33 (27.7) 26-30 95 30 (31.6) 3.670 0.453 31-35 50 18 (36.0) 36-40 26 7 (26.9) Marital status Single 207 17 (8.2) 0.063 0.996 Married 118 77 (65.3) Divorced/widowed 7 2 (28.6) Education level Illiterate 36 7 (19.4) Primary School 105 30 (28.6) 3.033 0.387 Secondary school 85 23 (27.1) Higher education 106 36 (34.0) Occupational status Government 62 22 (35.5) NGO 22 4 (18.2) 3.708 0.447 Private 126 35 (27.8) house wife 114 34 (29.8) house servant 8 1 (12.5) Number of children (parity) No children 62 9 (14.5) One 57 22 (38.6) 0.437 0.933 Two 55 18 (32.7) Three and above 21 9 (42.8) Gestational week 1-12 week 77 26 (33.8) 13-2 4 week 81 24 (29.6) 7.879 0.069 25-40 week 37 16 (43.2) No. of people in house hold Two 4 2 (50.0) Three 76 26 (34.2) 2.479 0.140 Four 138 36 (26.1) Greater than four 114 32 (28.1) Gravidity/no. of pregnancy One 91 28 (30.8) Two 61 24 (39.3) 8.314 0.140 Greater than three or 41 14 (34.1) equal to three Pregnancy Pregnant 195 66 (33.8) 5.589 0.020* Non pregnant 137 30 (21.9) Habit of alcohol drinking Yes 6 1 (16.60 No 325 95 (29.1) 0.446 0.677 Smoking habit Yes 1 0 (0.0) No 331 96 (29.0) 0.468 1.000 Khat chewing habit Yes 2 0 (0.0) 0.818 1.000 No 330 96 (29.0) Drinking coffee & tea Yes 270 77 (28.5) 0.757 No 62 19 (30.6) 0.111 History of gastrointestinal illness Yes 190 66 (34.7) 7.323 0.007 * No 142 30 (21.1) Hyperemesis gravidarum Yes 145 61 (29.6) 5.259 0.001 * No 50 5 (9.1) water for drinking purpose pipe water 331 96 (29.0) Tanker 1 0(0.0) 0.408 1.000 Presence of intestinal parasite Negative 261 72 (27.6) 1.049 0.306 positive 71 24 (33.8) Anemia status Anemic 61 44 (72.1) 68.61 0.001* Non anemic 271 52 (19.2) Note. * Statistically significant, HPSA: H. pylori stool antigen test, and NGO: nongovernmental organization. Table 3: Multivariate logistic regression showing adjusted odds ratio between H. pylori infection and associated risk factors among women of childbearing ages participated in the study in selected health centers, Addis Ababa, Ethiopia, April to October 2015 (n=332). Variables HPSA positive COR N n (%) (95% CI) Pregnancy status Pregnant 195 66 (33.) 1.570 (1.31,1.87) Non pregnant 137 30 (21.9) 1 Hyperemesis gravidarum Yes 145 61 (42.1) 6.536 (2.45, 17.43) No 50 5 (10.0) 1 Anemia status Anemic 61 33 (54.1) 0.257 (0.144, 0.458) Non anemic 271 63 (23.2) 1 Variables P-value AOR P-value (95% CI) Pregnancy status Pregnant <0.001 1.825 (1.42,2.15) 0.020 * Non pregnant Hyperemesis gravidarum Yes <0.001 7.028 (2.47,19.99) 0.018 * No Anemia status Anemic <0.001 0.177 (0.083,0.379) 0.003 * Non anemic AOD: adjusted odd ratio, COR: crude odd ratio, CI: confidence interval, and HPSA: Helicobacter pylori stool antigen test.
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|Title Annotation:||Research Article|
|Author:||Kitila, Kumera Terfa; Sori, Lemi Mosisa; Desalegn, Daniel Melese; Tullu, Kassu Desta|
|Publication:||International Journal of Chronic Diseases|
|Date:||Jan 1, 2018|
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