Treatment and clinical outcomes of acute glomerulonephritis among children admitted to the pediatric ward, Asella Teaching and Referral Hospital, Arsi, Ethiopia

doi:10.21203/rs.3.rs-3340540/v1

Download PDF

Research Article

Treatment and clinical outcomes of acute glomerulonephritis among children admitted to the pediatric ward, Asella Teaching and Referral Hospital, Arsi, Ethiopia

https://doi.org/10.21203/rs.3.rs-3340540/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Background

Acute glomerulonephritis is an acute kidney injury syndrome characterized by the sudden onset of edema and new-onset or worsening hypertension. It is common in school-aged children and typically presents with hematuria, edema, oliguria and varying degrees of renal insufficiency. This problem is particularly important in developing countries. Therefore, this study aimed to assess the treatment and clinical outcomes of AG among children admitted to the pediatric ward in Asella Teaching and Referral Hospital, Ethiopia.

Methods

A retrospective cross-sectional study design was conducted at the Asella Teaching and Referral Hospital pediatrics ward from September 2017 to June 2021. A simple random sampling technique was applied to select 282 study participants. Modified questionnaires based on a previous study were used to collect the data and then entered into Epi-info version 7.2.1.0 and exported to SPSS version 23 for further analysis.

Result

A total of two hundred eighty-two records of children diagnosed with acute glomerulonephritis were included in this study. The age range of the participating patients was 2 to 14 years. More affected patients were male. The most affected age group was between 6 and 10 years (55.3%). The most common clinical manifestation was facial edema (100%), and leg edema was 90.1%. The complications were hyperkalemia (10.6%), heart failure (9.9%) and anemia (9.2%). A total of 131 (92.9%) patients improved and were discharged within two weeks (positive outcome).

Conclusion

The highly affected age group was between 6 and 10 years, and most of the patients were admitted with different complications. Timely and proper intervention is necessary, and long-term follow-up should be performed in every patient.

Acute glomerulonephritis

Treatment

Clinical outcomes

Pediatrics

Ethiopia

Acute glomerulonephritis is characterized by the pathological process of acute inflammation or cellular proliferation of the glomeruli without a direct kidney infection (1). It is most commonly a sequela of the nephritogenic group A beta hemolytic streptococcus.

APSGN (Acute post streptococcal glomerulonephritis) is an immune-mediated disease associated with acute respiratory tract infections and skin infections with clinical manifestations persisting for more than 3 weeks (2). Post streptococcal glomerulonephritis (PSGN) is most common in children aged 5–12 years but is not common before the age of 3 years (3). The most common acute glomerulonephritis is post streptococcal glomerulonephritis, which is found mostly in developing countries and affects more children than adults, leading to acute kidney injury, and potentially increasing morbidity in children and threatening life (3).

The classical manifestation of acute glomerulonephritis is an acute nephritic syndrome that presents clinically with an abrupt onset of hematuria, in varying combinations with edema, hypertension, oliguria and differing degrees of diminishing renal function (4).

Acute glomerulonephritis was managed by both pharmacologically and non-pharmacologically. Non-pharmacologically by restricting salt and fluid, and regulating protein intake. In other ways, a ten day course of systemic antibiotic therapy with penicillin is recommended to limit the spread of nephrogenic organisms (5).

Despite the declining incidence of acute post- streptococcal glomerulonephritis in many developed countries, there is still a significant burden in developing countries (6). It is principally a disease of poverty because overcrowding and poor hygiene are prevail and are the significant causes of morbidity and mortality in developing countries with low socioeconomic status (7). Of the estimated 470,000 new annual cases of PSGN worldwide, 97% occur in regions of the world with poor socioeconomic status, with an annual incidence that ranges from 9.5 to 28.5 per 100,000 individuals (8, 9).

Major complications of acute glomerulonephritis are; acute kidney injury, hypertension, hyperkalemia, encephalopathy, heart failure, pulmonary edema, hyponatremia and anemia (10). In a study conducted in India, among 83 prospective studies showed clinical manifestations such as hematuria (80.6%), edema (91%), hypertensive emergency (19%), heart failure (11.1%) and encephalopathy (4.2%) (11). In a study performed in Mekelle among 334 children, 47.3% developed hyperkalemia, 64.1% developed hypertension and 11.7% developed acute kidney injury. From this, 73.1% had recovered immediately (3).

Regardless of the reduction in the worldwide incidence of PSGN, epidemics and clusters of cases of PSGN continue to appear. There is potential of increasing morbidity in children and threatening life if delayed diagnosis and subsequently inaccurate treatment occur. Although post streptococcal complications are known to be common among Ethiopian children, but little is known about the morbidity and mortality associated with APSGN. Therefore, our study aimed to do further study on this area.

Study design, setting and population

A retrospective cross-sectional study design was conducted in Asella Teaching and Referral Hospital, Arsi, Ethiopia. The town is located 175 km south of Addis Ababa. There are different governmental and nongovernmental institutions in the town. Currently, there is one referral hospital, and the hospital is estimated to service approximately 3.5 million people in Arsi and nearby zones. At pediatric department there were pediatrician, resident, general practitioner, nurses, and supportive staff who gives full time service. There were about 54 beds in the pediatric wards. The data collection was performed from October 25 to November 3, 2021. All pediatric patients diagnosed and admitted with acute glomerulonephritis in the pediatric ward during the study period were included in the study population. Patients with lost cards and cards with incomplete data were excluded.

Sample Size Determination and sampling procedure

The sample size for this study was determined using the single population proportion formula. The number of AGN patients admitted during this study period was two hundred eighty-two. A simple random technique was applied to select study participants.

Study Variable

Dependent variables

Treatment outcome (negative outcome and positive outcome)

Independent variables

Socio-demographic factors (age and sex), environmental factors (nutritional status, seasonal infection, residential area, time of presentation, length of hospital stay) and clinical features (facial edema, leg edema, ascites, acute kidney injury, heart failure, encephalopathy, hyperkalemia).

Data collection instrument and procedures

Data were collected by using a modified structured checklist. The checklist was adapted from reviewing different studies and previous similar studies, which were organized according to the objectives of the study. It includes information such as age, sex, ethnicity, nutritional status, seasonal infection, residential area, time of presentations, length of hospital stay, facial edema, leg edema, ascites, acute kidney injury, heart failure, encephalopathy, and hyperkalemia. For data collection, two clinical nurses were recruited.

Operational definition

Positive outcome

Those patients improved and were discharged within two weeks of hospital stay.

Negative outcome

Those patients who had no improvement and were not discharged within two weeks.

APSGN

Rapid deterioration of kidney functions due to inflammatory response following streptococcal infection (12).

Complication

A secondary disease or condition aggravating an already existing one.

Hypertension

BP > 95th percentile for age, sex, and height for children less than 13 years; or ≥ 130/80 mm Hg for adolescents ≥ 13 years old (13).

Acute kidney injury

Increase in serum creatinine by ≥ 0.3 mg/dL from baseline within 48 hr.; increase in serum creatinine to ≥ 1.5 times baseline within the prior 7 days; or urine volume ≤ 0.5 mL/kg/hr for 6 hr (14).

Encephalopathy

A generalized disorder of cerebral function that may be acute or chronic, progressive, or static (12).

Pediatric

The pediatric population defined in the American Academy of Pediatrics 2017 as that group of the population between birth and 18 years of age (15).

Data management and statistical analysis

Data were cleaned, coded and entered into Epi-info version 7.2.1.0 and were exported to SPSS version 23 for analysis. Descriptive statistics were conducted, and the results are presented using frequency tables, graphs and percentages. Linearity between independent and dependent variables was checked by scatter plot.

Socio-demographic factors

From the total study participants of 282, all cards had complete data with a response rate of 100%, and 54.6% of cases were males. The age range of the participants was 2 to 14 years, and the most affected age group was between 6 and 10 (55.3%). Among the study participants, 72.3% were from rural areas, and approximately 54.6% of infections occurred during the summer season. Of the study participants, 75.9% were well nourished, approximately 39.7% of participants had a history of sore throat, and 34.0% had a history of skin infection. Regarding the duration of infection, 75.9% of the patients presented to the hospital early (< 2 weeks), and 24.1% presented late (> 2 weeks) (Table 1).

Table 1: Socio-demographic characteristics of patients with acute glomerulonephritis in the pediatric ward at Asella Teaching and Referral Hospital, September 2017 to June 2021.

Variables

Category

Frequency

Percentage %

Age in years

2-5

27.0

6-10

156

55.3

11-14

17.7

Sex

Male

154

54.6

Female

128

45.4

Nutritional status

Well nourished

214

75.9

Malnourished

24.1

Seasonal infection

Winter

128

45.4

Summer

154

54.6

Source of infection

Sore throat

112

39.7

Skin

34.0

No known source

26.2

Residential area

Rural

204

72.3

Urban

27.7

Clinical manifestation

Facial edema was the most common clinical manifestation of the study participants, accounting for 100%, followed by leg edema, ascites, oliguria and seizure, accounting for 90.1%, 48.2%, 12.82% and 1.4%, respectively. Among the study participants, 75.9% developed hypertension, 45.4% of whom had stage II hypertension and 30.5% of whom had stage I hypertension (Table 2).

Table 2

Clinical manifestations of patients with acute glomerulonephritis in the pediatric ward at Asella Teaching and Referral Hospital, from September 2017 to June 2021
Clinical presentation	Frequency	Percentage %
Facial edema	282	100.0
Leg edema	254	90.1
Ascites	136	48.2
Cola colored urine	108	38.3
Oliguria	36	12.8
Seizure	4	1.42
BP-stage II	128	45.4
BP-stage I	86	30.5
BP-normal	30	10.6
Elevated BP	20	7.1

Complications and comorbidities

Among all study participants, hyperkalemia accounted for 30 (10.6%), heart failure accounted for 28 (9.9%), anemia accounted for 26 (9.2%), pulmonary edema accounted for 14 (5.0%), and encephalopathy accounted for 8 (2.8%). Among the study participants, approximately 11.3% had scabies, 9.2% had tinea capitis and 5.7% had pneumonia (Table 3).

Table 3

Complications and comorbidities of acute glomerulonephritis in the pediatric ward at Asella Teaching and Referral Hospital, from September 2017 to June 2021

Variables

Type

Frequency

Percentage %

Complication

No complication

176

62.4

Hyperkalemia

10.6

Heart failure

9.9

Anemia

9.2

Pulmonary edema

5.0

Encephalopathy

2.8

Comorbidities

Scabies

11.3

Tinea capitis

9.2

Pneumonia

5.7

Investigations (laboratory) results

For all study participants, urinalysis was performed for microscopic hematuria and proteinuria. Among them, proteinuria was found in 262 (92.9%) and dipstick hematuria in 270 (95.7%) of the study participants (Table 4).

Table 4

Frequency and percentage of dipstick hematuria and dipstick proteinuria patients with acute glomerulonephritis in the pediatric ward at Asella Teaching and Referral Hospital, September 2017 to June 2021
Variables	Category	Frequency	Percentage %
Dipstick Hematuria	++	112	39.7
	+++	82	29.1
	+	76	27.0
	Not detected	12	4.3
Dipstick Proteinuria	+	116	41.1
	++	102	36.2
	Trace	36	12.8
	Not detected	20	7
	+++	8	2.8

Among the study participants, 62.4% were reactive in the ASO titer, and 51.1% had increased blood urea nitrogen (> 7 mmol/l). Regarding serum creatinine, 44.0% had 1–3 mg/dl, and 2.8% of participants had serum creatinine > 3 mg/dl (Table 5).

Table 5

Serum creatinine, blood urea nitrogen and ASO titer of acute glomerulonephritis in the pediatric ward at Asella Teaching and Referral Hospital, from September 2017to June 2021
Variables	Category	Frequency	Percentage %
Serum Creatinine	< 1 mg/dl	134	47.5
	1–3 mg/dl	124	44.0
	Not done	16	5.7
	> 3 mg/dl	8	2.8
Blood Urea Nitrogen	> 7 mmol/l	72	51.1
	1–7 mmol/	61	43.2
	Not done	8	5.7
ASO titer	Reactive	176	62.4
	Non-reactive	106	37.6

Among the study participants with acute glomerulonephritis, 8.5% had serum sodium levels < 135 mmol/l, and 10.6% had elevated serum potassium levels > 5.5 mmol/l (Table 6).

Table 6

Serum sodium and potassium of acute glomerulonephritis in the pediatric ward at Asella Teaching and Referral Hospital from September 2017 to June 2021
Variables	Category	Frequency	Percentage %
Serum Sodium	135–145 mmol/l	168	59.6
	Not done	90	31.9
	< 135 mmol/l	24	8.5
Serum Potassium	3.5–5.5 mmol/l	162	57.5
	Not done	90	31.4
	> 5.5 mmol/l	90	10.6

Pharmacological Treatments

In the current study, all patients were treated with either oral or parenteral furosemide. Among these 42 patients treated with nifedipine, 26 patients were treated with hydralazine, and 4 patients were treated with nifedipine and enalapril together. Similarly, 105 patients were treated with amoxicillin, and the remaining patients were treated with ceftriaxone, ketoconazole and azithromycin (Table 7).

Table 7

Pharmacologic treatment of patients with acute glomerulonephritis in the pediatric ward at Asella Teaching and Referral Hospital, from September 2017 to June 2021
Pharmacologic treatment	Category	Frequency	Percentage %
Diuretic	Furosemide	282	100.0
Antibiotics	Amoxicillin	210	74.5
	Ceftriaxone	16	5.7
	Others	12	4.2
Antihypertensive	Nifedipine	84	29.8
	Hydralazine	52	18.4
	Nifedipine, enalapril	8	2.8
	Enalapril	4	1.4

Others (ketoconazole (2.8%), azithromycin (1.4%)

Treatment outcome and length of hospitalization

Among the study participants, 262 (92.9%) patients had improvement and were discharged within two weeks and the remaining 20 (7.1%) patients had no improvement (Fig. 1).

In the current study, two hundred eighty two patients were admitted with acute glomerulonephritis over a four year period from September 2017 to June 2021 which is a lower number of reports in Ethiopia than in a study conducted at Mekelle University which involved 334 records from September 2013 to August 2015. This may be due to a difference in the catchment population in the study area.

In this study, 262 (92.9%) patients had recovered from their illness immediately (positive outcome), which is similar to a study conducted in Mekelle University, Ethiopia (16).

The male 55.3% preponderance here agrees with previous reports in northern India (1.72:1) and Mekelle (60.5%) (16, 17). Among the age groups included in the study, acute glomerulonephritis was seen in the age group of 2 to 14 years. The age range is akin to earlier observations of 3 to 15 years reported in Nigeria (18). In index study, 72.3% of subjects were from rural areas, which could be the contributing factors (16).

In the present study sore throat (39.7%) was the leading source of infections, similar to other research performed in northern India (17). The majority (75.9%) of children with AGN were well nourished, which differed greatly from a study in Ibadan Nigeria, where 90% of patients had under nutrition, and a study at Mekelle University also suggested that approximately about 84.4% of children had under nutrition (5, 16).

With regard to the duration of infection, 75.9% of patients came to the hospital less than two weeks early, which differed from a study conducted at Mekelle University, where approximately 17.4% only presented to the hospital less than two weeks early (16). This may be due to increasing health seeking awareness of the population.

In this study, approximately 92.9% of patients were discharged within two weeks, which differed from the study conducted at Mekelle University, where 77.2% of patients stayed for longer than two weeks (16). This may be because of late presentation to the hospital and complications.

In this study, the major clinical manifestations were facial edema (100%), leg edema (90.1%), cola -colored urine (38.3%), ascites (48.2%), others (14.22%) and different stages of hypertension (elevated blood pressure 7.1%, stage I (30.5%), stage II (45.4%)). This is comparable with a study conducted in Odisha, which reported facial puffiness (97.1%), pedal edema (94.3%), oliguria (97.0%) and severe hypertension (71.4%) (19).

Acute kidney injury was the most common complication (46.8%), followed by hyperkalemia (10.6%), heart failure (9.9%), anemia (9.2), pulmonary edema (5.0%) and hypertensive encephalopathy (2.8%). This is different from studies conducted in Nigeria and Mekelle University, where hypertensive encephalopathy (7.1%) and pulmonary edema (33.3%) were the major complications, respectively (16, 19).

In the present study, there were few patients who presented with other comorbidities, such as scabies (11.3%), tinea capitis (9.2%) and pneumonia (5.7%).

In the current study, hematuria was observed in approximately 95.8% of patients, which is higher than that in the study performed in Odisha (25.7%) (19), and the nephrotic range proteinuria was 2.8%, which is lower than that in previous reports performed in Nigeria (26.7%) (18).

Approximately 62.4% of patients had reactive ASO titers, but this rate was lower than that in other studies, such as Odisha (78.1%), and higher than that in a study performed in Bangladesh (52.6%) (19, 20). All patients were treated with furosemide, additional antihypertensive drugs such as nifedipine (29.8%), hydralazine (18.4%), enalapril (1.4%) and both enalapril and nifedipine (2.8%). This is similar to previous studies (16).

In this study, 81.6% of patients took antibiotics. The majority of them took amoxicillin (74.5%), and the rest took ceftriaxone, azithromycin and antifungal ketoconazole. When this is compared to Odisha, all of the patients were treated with antibiotics. Penicillin was used in 34.3% of cases (19).

The highly affected age group was between 6 and 10 years. Most of the patients were admitted with different types of complications associated with acute glomerulonephritis. It can be presumed that although mostly recovered, AGN in children should not be taken as a benign condition. Timely and proper intervention is necessary, and long -term follow -up should be performed in every patient. Since the disease is common among school- age children, infection prevention strategies should be implemented through health education (personal hygiene, decreasing overcrowding and others) and family counseling on infection prevention at the home by maintaining hygiene, avoiding indoor cooking and coming early to the hospital to prevent complications of acute glomerulonephritis. Treatment of other comorbidities, such as scabies and streptococcal pharyngitis. Early treatment of fatal complications should be performed to prevent further morbidity and mortality from acute glomerulonephritis.

As a retrospective study design as its review of charts, some information is bound to be missing.

AGN – Acute glomerulonephritis

AKI –Acute kidney injury

APSGN-Acute post streptococcus glomerulonephritis

A.T.R.H – Asella Teaching and Referral Hospital

ASO-Anti streptolysin O

BP- Blood pressure

BUN-Blood urea nitrogen

C3-Complement three

CRP-C reactive protein

GAS-Group A streptococcus

HMIS-Health management information system

HTN-Hypertension

IV-Intravenous

IRB- Internal review board

PICU-Pediatric intensive care unit

PSGN-Post streptococcal glomerulonephritis

Ethical Considerations

Prior to the study, ethical clearance or a supportive letter was taken from the Arsi University College of Health science the pharmacy department. The medical record unit was informed about the objectives and purpose of the study, and written consent was obtained from the head. Confidentiality of information was assured.

Availability of data and materials

All relevant data are included in the article. The dataset of this study is available from the corresponding authors upon reasonable request.

Acknowledgements

The authors would like to acknowledge the Asella Teaching and Referral Hospital for their full cooperation to take our study in their institutions, facilitating the study setting and for the unreserved offer of their medical equipment required for the data collection.

Funding

No specific funding for the study.

Contributions

SD conceptualize and designed the study, conducted the analysis, interpret and write the first draft of the paper for publication. YD and TA were involved in the data analysis and interpret the data and reviewed the manuscript for publication. All authors read and approve the final manuscript.

Ethics declarations

Ethics approval and consent to participate

For the current retrospective study the need for informed consent was approved by Arsi University Referral Hospital ethics committee/IRB. To review each patient’s card, permission letters were obtained from Arsi University Referral Hospital administrative office. All experimental protocols were approved by Arsi University Referral Hospital ethics committee/IRB. Privacy and confidentiality of information were properly kept. All methods were carried out under relevant guidelines and regulations. All experimental protocols were approved by the Arsi University Referral Hospital.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Field MJ, Pollock C, Harris D. The Renal System E-Book: Systems of the Body Series: Elsevier Health Sciences; 2011.
Satoskar AA, Parikh SV, Nadasdy T. Epidemiology, pathogenesis, treatment and outcomes of infection-associated glomerulonephritis. Nature Reviews Nephrology. 2020;16(1):32-50.
Gebreyesus LG, Aregay AF, Gebrekidan KG, Alemayehu YH. Factors associated with treatment outcome of acute post streptococcal glomerulonephritis among patients less than 18 years in Mekelle City, Public Hospitals, North Ethiopia. BMC Research Notes. 2018;11(1):1-6.
Hashmi MS, Pandey J. Nephritic Syndrome. StatPearls [Internet]. 2020.
Asinobi A, Ademola A, Nwankwo A. Childhood acute glomerulonephritis in Ibadan Nigeria. Nigerian Journal of Paediatrics. 2020;47(4):345-52.
Eison TM, Ault BH, Jones DP, Chesney RW, Wyatt RJ. Post-streptococcal acute glomerulonephritis in children: clinical features and pathogenesis. Pediatric Nephrology. 2011;26(2):165-80.
Rawla P, Padala SA, Ludhwani D. Poststreptococcal Glomerulonephritis: StatPearls Publishing, Treasure Island (FL); 2021 2021.
Alhamoud MA, Salloot IZ, Mohiuddin SS, AlHarbi TM, Batouq F, Alfrayyan NY, et al. A Comprehensive Review Study on Glomerulonephritis Associated With Post-streptococcal Infection. Cureus. 2021;13(12).
Steer AC, Danchin MH, Carapetis JR. Group A streptococcal infections in children. Journal of paediatrics and child health. 2007;43(4):203-13.
Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group A streptococcal diseases. The Lancet infectious diseases. 2005;5(11):685-94.
Marshall CS, Cheng AC, Markey PG, Towers RJ, Richardson LJ, Fagan PK, et al. Acute post-streptococcal glomerulonephritis in the Northern Territory of Australia: a review of 16 years data and comparison with the literature. The American journal of tropical medicine and hygiene. 2011;85(4):703.
Parthasarathy A, Menon P, Nair M. IAP Textbook of pediatrics: Jaypee Brothers Medical Publishers; 2019.
Sharma AK, Metzger DL, Rodd CJ. Prevalence and severity of high blood pressure among children based on the 2017 American Academy of Pediatrics Guidelines. JAMA pediatrics. 2018;172(6):557-65.
Kellum JA, Lameire N, Aspelin P, Barsoum RS, Burdmann EA, Goldstein SL, et al. Kidney disease: improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury. Kidney international supplements. 2012;2(1):1-138.
Armstrong SC, Bolling CF, Michalsky MP, Reichard KW, Haemer MA, Muth ND, et al. Pediatric metabolic and bariatric surgery: evidence, barriers, and best practices. Pediatrics. 2019;144(6).
Gebreyesus LG, Aregay AF, Gebrekidan KG, Alemayehu YH. Factors associated with treatment outcome of acute post streptococcal glomerulonephritis among patients less than 18 years in Mekelle City, Public Hospitals, North Ethiopia. BMC research notes. 2018;11:1-6.
Rajajee S. Post-streptococcal acute glomerulonephritis: a clinical, bacteriological and serological study. The Indian Journal of Pediatrics. 1990;57:775-80.
DixonUmo OT, Ikpeme EE, Kan KM. Clinical profile and excellent short-term treatment outcome of acute glomerulonephritis: a report from paediatric nephrology unit of university teaching hospital, Uyo, Nigeria. International Journal of Research in Medical Sciences. 2020;8(7):2612.
Behera MR, Patnaik L, Sahu SK. Clinical profile and immediate outcome of acute post-infectious glomerulonephritis in children: a hospital-based study. J Evolution Med Dent Sci. 2016;5:5529-3.
Bhuiyan ASI, Alam Z, Hasan KZ, Zaman MM, Zakaria M. A Clinical Profile and Immediate Outcome of Acute Glomerulonephritis (AGN) in Hospitalized Children. American Journal of Pediatrics. 2020;6(4):448-54.

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Treatment and clinical outcomes of acute glomerulonephritis among children admitted to the pediatric ward, Asella Teaching and Referral Hospital, Arsi, Ethiopia

Status:

Version 1

Abstract

Background

Methods

Result

Conclusion

Figures

Introduction

Methods and Materials

Study design, setting and population

Sample Size Determination and sampling procedure

Study Variable

Dependent variables

Independent variables

Data collection instrument and procedures

Operational definition

Data management and statistical analysis

Results

Socio-demographic factors

Clinical manifestation

Complications and comorbidities

Investigations (laboratory) results

Pharmacological Treatments

Others (ketoconazole (2.8%), azithromycin (1.4%)

Discussion

Conclusion and Recommendation

Limitations of the study

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1