Original article

Praca oryginalna

ANALYSIS OF SOCIAL AND MEDICAL PORTRAIT OF CHILDREN WITH PERTUSSIS, MENINGOCOCCAL INFECTIOUS, SCARLET FEVER AND ESTIMATION OF THEIR ASSIGNED PHARMACOTHERAPY

Oryna Detsyk, Iryna Fedyak, Iryna Bilyk

Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine

ABSTRACT

Introduction: The level of childhood bacterial diseases incidence does not have a downward trend.

The aim: Conduction of a sociological analysis of medical cards for children with pertussis, meningococcal infection (MI), scarlet fever, and evaluation of consumed pharmacotherapy according to real clinical practice in Ukraine.

Materials and methods: 1215 medical cards of inpatients; methods: sociological – document analysis, retrospective frequency.

Results: Among the cards of children with pertussis: 50.2% – female, 49.8%– male; by age children up to 1 year (49.3%) were prevailed. In 79.6% incidence – medium-hard form pertussis, 42.2% with complications. Among patients with MI by sex there were: 50.5 % – boys and 49.5% – girls; by age – children aged 1-4 (40.2%); the structure of generalized forms of MI: 40.2% – meningococcemia, 11.4% – meningitis, 48.4% – combination. Scarlet fever was more frequently: boys (56.4%), children aged 5-9 (44.7%), urban residents (79.7%); it was 93.4% of a medium-hard form. Most of medicines were prescribed to children with MI – 15.8 trade names per 1 person, it was prescribed 191 INN, most often – Sodium chloride (90.0%), Ascorbic acid (68.5%), Ceftriaxone (65.8%); patients with pertussis – 11.2, 196 INN (Chlorpromazine (69.1%), Dexamethasone (53.2%), Butamirate (51.8%)); scarlet fever – 9.3 medicines, 114 INN (local action Comb drug for throat diseases treatment (94.4%), Ceftriaxone (48.7%), Metamizole sodium (38.1%)).

Conclusions: Frequency analysis data of consumed pharmacotherapy in real pediatric practice in Ukraine shows the need for its further optimization in accordance with the principles of evidence-based medicine, the results of research on the socio-demographic characteristics of patients, forms and complications of course of the basic disease.

KEY WORDS: retrospective analysis, pertussis, meningococcal infection, scarlet fever, children

Wiad Lek 2019, 72, 9 cz II, 1802-1808

Introduction

The most widespread children bacterial infections (CBI) are pertussis, meningococcal infectious (MI), scarlet fever [1-4]. During the past ten years, there has been a significant increase in the pertussis incidence among children. Pertussis is a sharp infectious vaccine-controlled disease with airborne transmission mechanism. Its leading clinical symptom is protracted spasmodic cough [5-7]. Both in Ukraine and abroad, high incidence is registered among children of the first year of life, especially in infants who have not yet been vaccinated. At the same time young children have the highest risk of severe disease and complications. According to statistic data in Europe and North America, the prevalence of pertussis among high school children and adults is noted. The probability of getting sick after contact with a patient is very high – 90 % [8-13].

Unlike pertussis the MI belongs to uncontrolled infections and can cause both sporadic cases of the disease and epidemic outbreaks. This is an acute anthroponistic disease of the respiratory tract infections caused by meningococcus (Neisseria meningitidis) and is characterized by clinical polymorphism in the form of nasopharyngitis, purulent meningitis and sepsis [14-17]. In European region countries the mortality of MI is 9-12 %, in Ukraine the mortality rate varies from 14 to 17 %. It is generally accepted that the categories with the highest risk of MI development are newborns and children of the first year of life (since natural immunity against N. meningitidis is especially low), adolescents (due to their habits and behavior that promote interpersonal communication), travelers who have been staying for a long time in endemic regions. The susceptibility to MI is generally, the index of contagiousness is 10-15 % [18-23].

One of the known infectious children diseases with streptococcal etiology is scarlet fever. This is an acute anthropogenic infectious disease caused by β-hemolytic streptococcus group A and characterized by symptoms of general intoxication, sore throat and skin rash, susceptibility to septic and allergic complications. The main way of infectious transmission is airborne. It is possible contact way of infection through toys, things as well as through food. The lowest incidence rate is recorded in children of the first year of life (especially up to 6 months), in the blood of which antibodies that have been spread through the placenta are circulated. Contagiousness index of scarlet fever is 40 % [24-28].

Since infectious diseases remain one of the main causes of worldwide children mortality, the study of the socio-demographic characteristics of children suffering from pertussis, MI, scarlet fever is relevant for optimizing the provision of effective medical and pharmaceutical aid.

The aim

Conduction of a retrospective analysis of gender, age, social characteristics of children with pertussis, MI, scarlet fever at the age of 0-17; forms of diseases, complications, causes of patients discharge from hospitals; as well as the evaluation of drugs prescribed by doctors by frequency analysis based on real clinical practice in Ukraine.

Materials and methods

The sample collection consisted of 1 215 medical cards of the form № 003/o stationary patients with pertussis (A 37), meningococcal infection (A 39), scarlet fever (A 38) during 2009 – 2016, which were obtained by random selection from the archives of the 6 regional clinical children’s infectious hospitals in Vinnytsia, Ivano-Frankivsk, Kiev, Odessa, Ternopil and Kharkiv oblast. To work with archival materials with the preservation of the confidentiality of personal data of children were obtained permits of the chief doctors of each health care institution. It was used the sociological method of documents analysis (medical cards): formalized (quantitative) and content analysis (qualitative and quantitative method, which allowed quantification of medical cards by categories with subsequent interpretation of data). In addition, to determine the appropriateness of pharmacotherapy prescribed for patients to clinical protocols, the frequency method of clinical and economic research was used, which consisted in ranking of the medicines consumed by them by the frequency of use – in the whole set of appointments and among the names of medicines by international non-proprietary names (INN).

Results

Among 1 215 analyzed medical cards, there were 834 children with pertussis disease history, 184 – MI (generalized forms of meningococcemia, meningitis or their combination), 197 – scarlet fever. On average, children with pertussis were treated in hospital for 15±7 bed-days, for MI – 14±7 bed-days, for scarlet fever – 11±5 bed-days. According to the medical cards, demographic characteristics of sick children were studied, first of all – gender and place of residence (Fig. 1, 2).

The distribution of patients by gender (Fig. 1) showed that there were more boys with MI and scarlet fever than girls (p> 0.05). The distribution by the area of residence (Fig. 2) showed that the children with scarlet fever (79.7 %) and MI (56 %) lived in cities and children with pertussis – in villages (55.8 %) (p < 0.001).

By the age children with pertussis were prevailed in two categories – up to 1 year (49.3%) and from 1 to 4 years (31.8 %). The most often MI was found in children at the age of 1-4 (40.2 % of the sample). Among children with scarlet fever, patients aged 5-9 (44.7 %) and 1-4 (40.6 %) were prevailed. Thus, according to the research girls up to 1 year, which mostly were residents of villages got sick by pertussis more often. MI was prevailed in boys aged 1-4 years, and scarlet fever aged 5-9 years, both mostly city residents (p < 0.001) (Fig. 3).

By the severity criteria both pertussis and scarlet fever in contrast to the MI are divided into mild, medium-hard and severe forms (Fig. 4). The analysis showed that most of patients were with pertussis (79.6 %) and scarlet fever (93.4 %) of a medium-hard form. In the structure of meningococcal infection among generalized forms 40.2 % had meningococcal disease, 11.4 % – meningitis, and 48.4 % – their combination.

It was found that MI (87 %) and scarlet fever (87.3 %) were undergone without complications, 42.2 % of pertussis was complicated. 77 % of patients with MI were discharged with recovery and 3 persons were transferred to another hospital. 52.8 % of patients with pertussis and 40.1 % with scarlet fever left the hospital with an improvement. Unfortunately, 8.6% of children with pertussis and 6.6 % of children with scarlet fever did not continue their treatment in a hospital (Fig. 4).

Among the most widespread pertussis complications there were pneumonia (68.4 %), acute bronchitis (30.8 %). 10.8% of MI cases were complicated by an infectious-toxic shock, which made 64.5 % of the total complications, and 2.7 % – DIC-syndrome (16.1 %). The most widespread complications of scarlet fever were pyelonephritis (36.8 %), myocarditis (31.6 %), otitis (15.8 %) (Fig. 5).

According to the concomitant diseases rating which were discharged in medical cards of children with bacterial infections, the most common for three nosologies was such comorbidities as anemia (Table I).

The next stage of the research was to conduct a retrospective clinical and economic analysis of intended pharmacotherapy for children with pertussis, MI and scarlet fever. The results of the frequency analysis show that 9 317 prescriptions of 196 drugs according to international non-proprietary names (INN) were prescribed for children with pertussis, which was 11.2 per patient. Totally, patients with MI were assigned 191 names of drugs by the active substance. The total number of appointments is 2 908, and the number of appointments per patient is 15.8. For children with scarlet fever, 1 824 appointments were prescribed by 114 drugs (INN), for one patient – 9.3. Table II shows the TOP-10 drugs by the frequency of use for the treatment of each studied bacterial infections.

As indicated by the results of the frequency analysis, Ceftriaxone was included in TOP-5 INN antibacterial drugs that were most commonly used. In addition, children with scarlet fever (48.7 %) and MI (65.8 %) were most often taken this drug. In the pharmacotherapy of the pertussis this drug was the fifth (49.5 %). The analysis data indicate that patients with MI received a lot of infusions, and with pertussis – drugs for the cough attacks reduction and prevention (Chlorpromazine). Comparison of the results of real clinical practice with the Ukrainian protocol was evidenced by the absence of an effective formulary approach to the appointments of drugs to patients in Ukraine, since the list of actually consumed drugs is wider than legally recommended. Thus, the order of the Ministry of Health of Ukraine № 354 from 09.07.2004 “On approval of the Protocols for the diagnosis and treatment of children infectious diseases” [29] for the treatment of children suffering from pertussis it is recommended to use antibacterial medicines and aminazine. TOP-10 INN analysis for the treatment of patients with MI showed that according to the protocol for treatment of patients with MI (Ministry of Health of Ukraine Order № 737 from 12.10.2009 “The Protocol for the Treatment of Meningococcemia in Children” [30]), the following INN were prescribed: ceftriaxone, electrolytes in combination with other drugs, furosemide, dexamethasone, heparin. At the same time, the auxiliary therapy drugs (vitamins, probiotics, and dietary supplements) are not included in the recommendations of the regulatory document. The same applies to regulatory approaches to scarlet fever therapy which also contain no vitamins, probiotics, but also contain local antiseptic agents that accounted a significant proportion of Comb drug in accordance with the protocol requirements [29].

Discussion

According to the Guidelines for the public health management of pertussis in England (2018) macrolides (azithromycin and clarithromycin) are recommended to treat patients with pertussis. A number of researchers, namely: Marchant JM, Petsky HL, Morris PS, Chang [30], Altunaiji SM, Kukuruzovic RH, Curtis NC, Massie J [32], Cherry JD [11] have experimentally confirmed the advisability of using macrolides for pharmacotherapy of pertussis in children. Simultaneously, the results of real clinical practice analysis in Ukraine revealed the prevalence of cephalosporins, namely Ceftriaxone in the doctors’ prescriptions. On the other hand, a qualitative analysis of antibiotic therapy in patients with MI in Ukraine showed the same approach to its practice with evidence-based medicine. Since the use of Ceftriaxone or Cefotaxim is advisable in the treatment of patients with MI according to Zalmanovici Trestioreanu A, Fraser A, Gafter-Gvili A, Paul M, Leibovici L [34] and National Collaborating Center for Women’s and Children’s Health [15] publications, which show the results of this study. And for the treatment of patients with streptococcal infection, penicillins are drugs of choice, despite the more than 60-year period of their application [35]. Cephalosporins in the treatment of patients with scarlet fever are used while penicillin allergies and macrolides are also second-line drugs [36]. At the same time, the results of the analysis of the practice of prescribing antibiotics to patients with scarlet fever in Ukraine also showed the priority of Ceftriaxone over other antibacterial agents.

Consequently, data of the actual clinical pediatric practice for treatment of children with pertussis, MI, scarlet fever in Ukraine indicate the need for its further optimization both in relation to evidence-based therapy and pharmacoeconomics. The next stage of our research will be conducting of ABC- and VEN-analyzes.

Conclusions

The results of the study showed that 50.2 % of children’s medical cards belonged to women, 49.8 % to men; by age, children over 1 year were significantly more prevailed (49.3 %); the share of rural residents (55.2 %) was higher than urban (44.2 %). In 79.6% pertussis had a medium-hard form and 42.2 % had complications in the form of pneumonia (68.4 %) or acute bronchitis (30.8 %). The distribution of patients with meningococcal disease also did not reveal any gender differences: 50.5 % were boys and 49.5 % were girls, and there were more urban residents (56.0%); by the age there was predominance of children aged 1-4 years (40.2 %). In the structure of meningococcal infection among generalized forms 40.2 % had meningococcal disease, 11.4 % had meningitis, 48.4 % had a combination of them; 13 % of patients had complications among which the leader was an infectious-toxic shock (64.5 %). Scarlet fever was more widespread in boys (56.4 %) and children aged 5-9 years (44.7 %), among patients a significant prevalence of urban residents was found (79.7 %). This disease was 93.4 % in medium-hard form, among its complications pyelonephritis (36.8 %) and myocarditis (31.6 %) were predominated.

It was found that the largest number of medicines by INN was taken by children with MI – an average of 15.8 trade names of drugs, and in general this set of patients was assigned to 191 INN, among which Sodium chloride as a solvent (90.0 %), Ascorbic acid (68.5 %), Ceftriaxone (65.8 %) were leaders. The second place by the number of consumed drugs was taken by patients with pertussis (11.2, 196 INN), which were most commonly prescribed by Chlorpromazine (69.1%), Dexamethasone (53.2 %), Butamirate (51.8 %). One child with scarlet fever consumed on average 9.3 drugs (114 INN totally), whose ranking was led by the local route Comb drug for the treatment of throat (94.4 %), Ceftriaxone (48.7 %), Metamizole sodium (38.1 %).

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Authors’ contributions:

According to the order of the Authorship.

ORCID numbers:

Oryna Detsyk – 0000-0003-3979-9455

Iryna Bilyk – 0000-0002-4048-2820

Conflict of interest:

The Authors declare no conflict of interest.

CORRESPONDING AUTHOR

Iryna Bilyk

The Chair of Organization and Economics of Pharmacy and Drug Technology

Ivano-Frankivsk National Medical University

2 Galytska str., Ivano-Frankivsk, 76000, Ukraine

tel: +380987242088

e-mail: bily4ka@ukr.net

Received: 12.06.2019

Accepted: 30.08.2019

Fig.1. Gender distribution of children with bacterial infections

Fig. 2. Distribution of children suffering from children bacterial diseases by area of residence

Fig. 3. Distribution of children suffering from children bacterial diseases by age

Fig.4. Distribution of medical cards of children with bacterial infections by criteria of severity, presence of complications, reason of discharge from hospital

Fig. 5. The most widespread complications of pertussis (a), MI (b) and scarlet fever (c) in children

Table I. TOP-10 concomitant diseases that accompanied the diagnosis of pertussis, MI, scarlet fever in children aged 0-17 years

Pertussis

МІ

SF

1.

Anemia

Anemia

Anemia

2.

Foramen ovale (heart)

Pneumonia

Urinary tract infection

3.

Diseases of the digestive system

Herpesviral infections

Adenoiditis

4.

Thymomegaly

Angiopathy of eye retina

Biliary dyskinesia

5.

Ascariasis

Gastroenteric fermentopathy

Ascariasis

6.

Pinworm infection

Pinworm infection

Table II. TOP-10 drugs (INN) by the frequency of appointments

Pertussis

МІ

Scarlet fever

INN

% patients that have taken drugs

% in total summation of appointments

INN

% patients that have taken drugs

% in total summation of appointments

INN

% patients that have taken drugs

% in total summation of appointments

Chlorpromazine

69.1

6.2

Sodium chloride

90.0

5.5

Comb drug

94.4

10.2

Dexamethasone

53.2

4.8

Ascorbic acid

68.5

4.3

Ceftriaxone

48.7

5.3

Butamirate

51.8

4.6

Ceftriaxone

65.8

4.2

Metamizole sodium

38.1

4.1

Drotaverine

49.9

4.5

Lactic acid producing organisms

62.0

3.9

Loratadine

35.0

3.8

Ceftriaxone

49.5

4.4

Electrolytes in combination with other drugs

61.4

3.9

Glucose

32.5

3.5

Procaine

45.8

4.1

Furosemide

60.9

3.9

Ibuprofen

Lactic acid producing organisms

30.5

3.3

Comb drug

45.7

4.1

Dexamethasone

54.4

3.4

Sodium chloride

29.4

3.2

Clemastine

45.5

3.9

BAS

46.7

3.0

Ascorbic acid

Cocarboxylase

28.9

3.1

Magnesium sulfate

42.8

3.8

Heparin

46.2

2.9

Desloratadine

27.4

3.0

BAS

34.7

3.1

Cocarboxylase

45.7

2.9

Diphenhydramine

BAS

26.9

2.9