Title 18. COMMONLY OCCURRING COMMUNICABLE DISEASES - Typhoid.pdf ✅

PHARMD GURU Page 1 TYPHOID INTRODUCTION: Typhoid fever is also called enteric fever. It is an acute infectious illness associated with fever that is most often caused by the Salmonella typhi bacteria. It can also be caused by Salmonella paratyphi, a related bacterium that usually leads to a less severe illness. The bacteria are deposited through fecal contamination in water or food by a human carrier and are then spread to other people in the area. Typhoid fever is rare in industrial countries but continues to be a significant public health issue in developing countries. PATHOPHYSIOLOGY: All the pathogenic Salmonella species, when present in the gut are engulfed by phagocytic cells, which then pass them through the mucosa and present them to the macrophages in the lamina proprietor. Non-typhoidal salmonellae are phagocytized throughout the distal ileum and colon. With toll-like receptor (TLR)–5 and TLR- 4/MD2/CD-14 complex, macrophages recognize pathogen-associated molecular patterns (PAMPs) such as flagella and lipopolysaccharides. Macrophages and intestinal epithelial cells then attract T cells and neutrophils with interleukin 8 (IL-8), causing inflammation and suppressing the infection. COMMONLY OCCURRING COMMUNICABLE DISEASES
PHARMD GURU Page 2 In contrast to the non-typhoidal salmonellae, S typhi and paratyphi enter the host's system primarily through the distal ileum. They have specialized fimbriae that adhere to the epithelium over clusters of lymphoid tissue in the ileum (Peyer patches), the main relay point for macrophages traveling from the gut into the lymphatic system. The bacteria then induce their host macrophages to attract more macrophages. S typhi has a VI capsular antigen that masks PAMPs, avoiding neutrophil-based inflammation, while the most common paratyphi serova, paratyphi A, does not. This may explain the greater infectivity of typhi compared with most of its cousins. Typhoidal salmonella co-opt the macrophages' cellular machinery for their own reproduction as they are carried through the mesenteric lymph nodes to the thoracic duct and the lymphatics and then through to the reticuloendothelial tissues of the liver, spleen, bone marrow, and lymph nodes. Once there, they pause and continue to multiply until some critical density is reached. Afterward, the bacteria induce macrophage apoptosis, breaking out into the bloodstream to invade the rest of the body.
PHARMD GURU Page 3 The bacteria then infect the gallbladder via either bacteremia or direct extension of infected bile. The result is that, the organism re-enters the gastrointestinal tract in the bile and reinfects Peyer patches. Bacteria that do not reinfect the host are typically shed in the stool and are then available to infect other hosts. SYMPTOMS AND COMPLICATIONS: Symptoms usually appear 1 or 2 weeks after infection but may take as long as 3 weeks to appear. Typhoid usually causes a high, sustained fever, often as high as 40°C (104°F), and extreme exhaustion. Other common symptoms include:  Constipation,  Cough,  Headache,  Loss of appetite,  Stomach pains,  Sore throat. Rarer symptoms include:  Bleeding from the rectum,  Delirium,  Diarrhoea.  Temporary pink spots on the chest and abdomen
PHARMD GURU Page 4 DIAGNOSIS: Infection with typhoid or paratyphoid fever results in a low-grade septicemia. It is diagnosed as follows: DIFFERENTIAL DIAGNOSIS: The group of symptoms which most clearly suggests the diagnosis of typhoid fever is:  Gradually increasing fever with evening exacerbation and morning remission.  General malaise with headache.  Furred tongue with red edges and tip.  Epistaxis.  Relatively slow pulse (possibly dicrotic).  Abdominal distension with increased bowel sounds.  Tenderness in the right iliac fossa on firm pressure.  A roseolar eruption confined principally to the abdomen and chest.  Splenomegaly.  Bronchial catarrh. The differential diagnosis of this group of symptoms will depend on travel history and may include a wide variety of tropical and non-tropical causes of fever and rash. Always consider co-existent malaria or schistosomiasis and others. ORGANISM CULTURE:  Diagnosis is made by culturing the organism. This may be obtained from stool or other sources.  Blood cultures are only positive in 40- 60% of cases. However, this may be enhanced to above 80% using two sets of blood cultures and modern methods.  The most sensitive source (90% isolation rate) is bone marrow aspiration.  Isolation of S. typhi is highest in the first week and becomes more difficult as time passes. SEROLOGY:  The traditional serological test is Widal's test. It measures agglutinating antibodies against flagellar (H) and somatic (O) antigens of S. typhi.