Discussion

In this study, acute rheumatic fever prevalence was similar in both gender groups. This finding is compatible with previous studies. ^{Reference Lawrence, Carapetis, Griffiths, Edwards and Condon12,Reference Rothenbühler, O’Sullivan and Stortecky13} A previous study demonstrated the increased risk for acute rheumatic fever in crowded households. ^{Reference Jaine, Baker and Venugopal14} Our study exposed the low parental education level and socio-economic status of the patients with acute rheumatic fever. Economic disadvantage and low education level of the parents were shown to be risk factors for acute rheumatic fever. ^{Reference Riaz, Selim, Karim, Chowdhury, Chowdhury and Rahman15} However, number of individuals living at home is claimed to be the most significant risk factor. ^{Reference Carapetis, Beaton and Cunningham16} In the present study, approximately 85% of patients with acute rheumatic fever were diagnosed with carditis by echocardiography. This relatively high rate of carditis actually indicates that both clinical and subclinical carditis cases were included. Clinical carditis is being diagnosed in 50–70% of acute rheumatic fever cases, whereas subclinical carditis was diagnosed in only 12–21% of cases. ^{Reference Tubridy-Clark and Carapetis4} Both clinical and subclinical carditis are currently considered as the major criterion for acute rheumatic fever. Relatively higher rate of carditis in our study compared to previous studies might be due to the inclusion of the patients diagnosed in both paediatric and adult cardiology clinics. Our study revealed that mitral and aortic valves were involved in about two-thirds and one-third of the patients, respectively. The mitral valve was most commonly involved, and the aortic valve was the second. ^{Reference Carapetis, Beaton and Cunningham16}

Approximately 15% of patients with acute rheumatic fever were diagnosed with chorea, and all the patients with chorea presented in the first acute rheumatic fever attack. Majority (96%) of the patients with chorea had carditis in the first acute rheumatic fever attack, and chorea was not observed in subsequent acute rheumatic fever attacks. In previous studies, chorea was generally diagnosed after 1–3 months following the first acute rheumatic fever attack, whereas the rate was reported to be as low as 10–30%. However, most studies included only clinically relevant carditis. When subclinical involvement is taken into account, it was asserted that up to 90% of patients with chorea also suffered from carditis. ^{Reference Carapetis, Beaton and Cunningham16–Reference Swedo, Leonard and Schapiro18}

The female gender and the high number of children at home were determined as independent predictors for the development of carditis in any of the acute rheumatic fever attacks in this study. Although acute rheumatic fever affects both genders equally, it has been shown that the development of carditis is more common in female gender. ^{Reference Karthikeyan and Guilherme1,Reference Carapetis, Beaton and Cunningham16} Having four or more siblings appeared to be an increased risk factor for carditis in previous studies. ^{Reference Jaine, Baker and Venugopal14,Reference Carapetis, Beaton and Cunningham16} In the current study, economic status of the families with and without carditis was similar. There is no doubt that rheumatic heart disease and poverty are related, and acute rheumatic fever should be regarded as one of the diseases of social injustice. ^{Reference Rothenbühler, O’Sullivan and Stortecky13} Overcrowded habitat is the best-identified factor among the environmental risk factors. Thus, it is argued that the crowded living environment poses a risk rather than the economic situation itself. ^{Reference Omurzakova, Yamano and Saatova19} Our findings vehemently supported this view.

Riaz et al. showed that low maternal literacy was associated with both acute rheumatic fever and rheumatic heart disease. ^{Reference Riaz, Selim, Karim, Chowdhury, Chowdhury and Rahman15} This relationship was not shown in another study in different geographic site. ^{Reference Dobson, Steer, Colquhoun and Kado20} A clear association was not found for the education levels of fathers as well. ^{Reference Coffey, Ralph and Krause21} In light of our data, neither maternal nor paternal education level had an effect on the development of carditis.

Breastfeeding for less than 6 months appeared to be associated with frequent upper respiratory tract infections. This can be attributed to the fact that lengthy breast milk intake improves the microbial flora of the nasopharynx and consequently protects it from infections. ^{Reference Biesbroek, Bosch and Wang8} In addition, it is well documented that effective breast milk intake reduces otitis media which is caused by similar microorganisms in upper respiratory tract infection. ^{Reference Duncan, Ey, Holberg, Wright, Martinez and Taussig22,Reference Abrahams and Labbok23} While carditis was seen less frequently in patients who breastfed for less than six months in the first acute rheumatic fever attack, these patients were equally vulnerable to recurrent acute rheumatic fever.

Carditis develops approximately three weeks after upper respiratory tract infection, when the protective immune response against GAS antigens generally causes damage to the heart muscle and valves via cross-reaction. Positive correlation was found between the severity of this immune response and the severity of acute rheumatic fever. While the humoral immune response is evident in the first week of acute rheumatic fever, the cellular immune response becomes prominent in the following weeks. Carditis development after acute rheumatic fever is thought to be dominated by cellular immune response later than three weeks. ^{Reference Carapetis, Beaton and Cunningham16} Detection of T-cell clones stimulated by streptococcal M protein and cardiac myosin epitopes in samples obtained from the valves of the patients elucidated the role of cellular immunity. In addition, it is claimed that these T-cell accumulations in the valves contribute to the granulomatous reaction. ^{Reference Cunningham24}

Studies have shown that breast milk plays an important role in the development of the cellular immunity, the response to vaccines, and the development of the thymus gland. The number of memory B cells decreases with breast milk intake, while the number of memory T cells increases significantly. ^{Reference Jansen, van den Heuvel and van Zelm25}

Breast milk intake is required for the proper development of intestinal microbiota. It has been shown that the intestinal microbiota increases the secretion of secretory Ig A, augments the helper T2 cell response, and activates regulatory T cells. ^{Reference Goldman26,Reference Cerf-Bensussan and Gaboriau-Routhiau27} In addition, thanks to the immunoglobulins, nucleotides, lactoferrin, and lymphocytes in breast milk, which are protective against infections.

Decreased frequency of carditis in the first acute rheumatic fever episode who received breast milk for less than six months may be attributed to the underdevelopment of the cellular immune system, due to the low or no intake of breast milk in these patients. The response of an immature immune system to GAS antigens will be weak. Considering the mechanism of acute rheumatic fever carditis, the severity of the immune response will determine the development of carditis. Although breastfeeding less than six months is seemingly an advantage against developing carditis in the first acute rheumatic fever attack, the fact that these patients lose this advantage in recurrent attacks illustrates the importance of enough breast milk intake. Although carditis did not develop in the first acute rheumatic fever attack in those who received breast milk for less than 6 months, the relative increase in the development of carditis in subsequent recurrent attacks can be explained by the memory feature of the cellular immune response. As in vaccines that cause cellular immune response, symptoms and immune response that develop at a mild level during vaccination create a distinct immune response against the microorganism, when they encounter the same microorganism again. ^{Reference Saso and Kampmann28}

Cumulative frequency of carditis during recurrent acute rheumatic fever attacks appears to be not altered by the breastfeeding duration. However, considering all the beneficial properties of breast milk, an optimal period of breastfeeding should always be encouraged.