Dr Chandana Chandran
- Enteric fever (typhoid fever) is a severe multisystemic infection caused by Salmonella Typhi. Similar illness can be caused by related but less virulent Salmonella Paratyphi (paratyphoid fever). Enteric fever is a collective term and refers to all illnesses caused by these organisms. The disease is characterized in endemic areas by the classic prolonged high grade fever, sustained toxemia, gastrointestinal symptoms and splenomegaly. Enteric fever is potentially fatal, if untreated.
- Enteric fever remains endemic in many developing countries. Given the ease of modern travel, cases are regularly reported from most developed countries, usually from returning travellers.
- The organisms are gram- negative, motile and non- spore forming bacilli.
- The incidence of typhoid fever has shown a marked decrease in developed countries as a result of good public health.
- The disease is transmitted orally, through the consumption of contaminated food, water or milk.
- The sources of infection are patients suffering from the disease or the excreta of carriers.
- Fomites and the housefly also disseminate the infection.
- About 20- 30% of typhoid fever cases occur in children below 10 years.
- Seasonal variations occur with peak incidence in the summer months.
AIM AND OBJECTIVES
- To study in depth about clinical presentation of enteric fever.
- To describe the epidemiology, pathology of enteric fever.
- To describe the complication and investigation of enteric fever.
- To understand and establish the efficiency of homoeopathic treatment in enteric fever.
- To understand the homoeopathic approach to enteric fever in children.
- To get the miasmatic understanding of enteric fever in children.
- To find out the early diagnosis in children.
- Neonatal enteric fever is a rare but life- threatening illness. Patients may present with varying severity.
- Salmonella enteric serotype Typhi causing more severe illness than Salmonella Enterica serotype Paratyphi A.
- Salmonella enteric serotype Paratyphi A is considered to cause milder infection with fewer complications. 
- For the developing countries of the tropics and subtropics, it continues to be a big public health problem as the sanitation and public health standards are poor.
- Multidrug resistant (MDR) typhoid fever shows up a changed clinical pattern and a higher rate of complications (20%). 
REVIEW OF LITERATURE
- Enteric fever is the term used to describe the systemic disease caused by the enteric organisms called salmonella. When the involved organism is Salmonella Typhi, the disease is specifically called typhoid fever.
- The other organisms that can cause enteric fever are Salmonella Paratyphi A, B, C etc. 
- Salmonella Typhi is excreted in the feces of infected persons.
- A person with active typhoid fever may also spread the organism through urine, respiratory secretions or vomitus.
- The food can be contaminated by flies which carry the bacilli from feces of an infected or carrier individual.
- Contaminated water or unpasteurized milk, are the other sources of infection.
- Environmental factors Transmission of S. Typhi is dependent on a multitude of environmental, social, and cultural factors. Cases occur more frequently during summer and rainy season, peaking with the onset of monsoons.
- Proper and adequate supply of potable water, proper excreta disposal system, hygienic personal and food habits, practicing of strict hand washing, pasteurization of milk, and health awareness are instrumental in preventing its transmission. Low socio economic groups who may not have access to the above mentioned facilities are more prone to suffer from typhoid fever. 
- Typhoid fever is caused by enteric serovar Typhi (S. Typhi), a gram- negative bacterium.
- A very similar but often less- severe disease is caused by Salmonella Paratyphi A and rarely by Salmonella Paratyphi B (Schotmulleri) and Salmonella Paratphi C (Hirschfeldii).
- The ratio of disease caused by S. Typhi to that caused by S. paratyphi is approximately 10:1, although the proportion of S. Paratyphi A infections I increasing in some parts of the world for no reasons that are unclear.
- Although S. Typhi shares many genes with Escherichia coli and at least 95% of genes with S. Typhimurium, several unique gene clusters known as pathogenicity islands and other genes have been acquired during evolution.
- The inactivation of single genes, as well as the acquisition or loss of single genes or large islands of DNA, may have contributed to host adaptation and retriction of S. Typhi.
- One of the most specific gene products is the polysaccharide capsule Vi (virulence), which is present in approximately 90% of all freshly isolated S. Typhi and has a protective effect against the bactericidal action of the serum of infected patients. 
- Typhi can survive at extremely low freezing temperature and drying, and therefore, can be transmitted through ice, frozen foods, and dust. 
- Children are typically infected with S. Typhi and S. Paratyphi through contaminated food and beverages. Infective dose is 105 to 108
- After ingestion by the host, the bacteria invade through the gut and multiply within the mononuclear phagocytic cells in the liver, spleen, lymph nodes, and Peyer’s patches in ileum. 
- Typhi crosses the intestinal mucosal barrier after attachment to the microvilli by an intricate mechanism involveing membrane ruffling, actin rearrangement, and internalization in an intracellular vacuole.
- In contrast to NTS, S. Typhi expresses virulence factors that allow it to downregulate the pathogen recognition receptor- mediated host ileum, S. Typhi can traverse the intestinal barrier through several mechanisms, including the M cells in the follicle- associated epithelium, epithelial cells and dendritic cells. At the villi, Salmonella can enter through the M cells or by passage through or between compromised epithelial cells.
- On contact with the epithelial cell, S. Typhi assembles type III secretion system encoded on SPI-I and translocates effectors into the cytoplasm. These efferctors activate host Rho guanosine triphosphatases, resulting in the rearrangement of the actin cytoskeleton into membrane ruffles, induction of mitogen- activated protein kinase pathways, and desabilizaaion of tight junctions.
- Changes in the actin cytoskeleton are further modulated by the actin- binding proteins SipA and SipC and lead to bacterial uptake.
- Mito- activation protein kinase signaling activates the transcription factors activator protein- 1 and nuclear factor- kB, which trun on production of IL- 8.
- The destabilization of tight junctions allows the transmigration of polymorphonuclear leu kocytes from the basolateral surface to the apical surface, paracellular fluid leakage, and access of bacteria to the basolateral surface. Shortly after internalization of S. Typhi by macropinocytosis, salmonellae are enclosed in a spacious phagosome that is formed by membrane ruffles.
- Later, the phagosome fuses with lysosomes, acidifies, and shrinks to become adherent around the bacterium, forming the Salmonella containing vacuole. type III secretion system encoded on SP1-2 is induced within the Salmonella-containing vacuole and translocates effector proteins SifA and PipB2, which contribute to Salmonella induced filament formation along microtubules.
- The S. Typhi toxin has been isolated and characterized composed of 2 A subunits, PltA and CdtB, which are homologs of the A subunits of the pertussis and cyto lethal distending toxins, respectively. Its single B subunit, PltB, is a homolog of 1 of the components of the heteropentameric B subunit of pertussis toxin.
- Although the cellular targets of the adenosine diphosphate- ribosyl transferase activity of PltA have not yet been identified, CdtB is a DNase that inflicts DNA damage and induces cell-cycle arrest.
- Typhi produces typhoid toxin only within mammalian cells, and the toxin is then ferried to the extracellular environment by a unique transport mechanism that involves vesicle carrier intermediates. These findings open the door to future opportunities for developing diagnostic and preventive strategies.
- After passing through the intestinal mucosa, S. Typhi organisms enter the mesenteric lymphoid system and then pass into the blood stream via the lymphatics. This primary bacteremia is usually asymp tomatic, and blood culture results are frequently negative at this stage of the disease. The bloodborne bacteria are disseminated throughout the body and are thought to colonize the organs of the reticuloendo thelial system, where they may replicate within macrophages.
- After a period of bacterial replication, S. Typhi organisms are shed back into the blood, causing a secondary bacteremia that coincides with the onset of clinical symptoms and marks the end of the incubation period.
- It is thought that several virulence factors, including type III secretion system encoded on SPI-2, may be necessary for the virulence properties and ability to cause systemic infection. The surface Vi poly saccharide capsular antigen found in S. Typhi interferes with phagocytosis by preventing the binding of C3 to the surface of the bacterium. The ability of organisms to survive within macrophages after phagocy tosis is an important virulence trait encoded by the PhoP regulon and may be related to metabolic effects on host cells. The occasional occurrence of diarrhea may be explained by the presence of a toxin related to cholera toxin and E. coli heat-labile enterotoxin. The clinical syndrome of fever and systemic symptoms is produced by a release of proinflammatory cytokines (IL-6, IL-1B, and TNF-a) from the infected cells.
- In addition to the virulence of the infecting organisms, host factors and Immunity may also play an important role in predisposition to infection. There is an association between suscepubility to typhoid fever and human genes within the major histocompatibility complex class II and class III loci. Patients who are infected with HIV are at significantly higher risk for clinical infection with S. Typhi and S Paratyphi. Similarly, patients with Helicobacter pylori infection have an increased risk of acquiring typhoid fever. 
- The incubation period is 14 days with a range of 3 to 60 days.
- No age is exempt but typhoid fever is less common in children under 2 years due to less chances of exposure to infected food from outside the house.
FIRST WEEK OF ILLNESS
- Classically, the onset is gradual.
- The step ladder pattern of fever characteristically seen in adults is not seen.
- The onset may be sudden with rapid elevation of temperature, often with headache and vomiting.
- The fever is generally continuous with little diurnal variation.
- Remittent fever is not unusual in children.
- Constipation is frequent but some patients may present with diarrhea and abdominal pain.
- The tongue is often coated in the center and clear at margins.
- Bradycardia is not always present in children.
- Pulse rate may rise proportionately to the height of temperature.
- Typhoid rash may not be evident on pigmented skin. When present it occurs on 6th day of the illness. It comes in crops, which appear as rose spots and is observed only for a few hours. The rose spots fade on pressure.
SECOND AND THIRD WEEK
- The abdomen is usually distended and gives a tympanitic note on gentle tapping. This is a useful sign.
- The spleen is palpable 1 or 2 cm below the costal margin in over two-third of patients.
- Rales are often heard over bases of lungs.
- If toxemia is severe, the sensorium is dull with apathy and stupor.
- The child may have muttering delirium and may pick at bed clothes. This peculiar state is called typhoid state.
- The relapse rate is 10- 20 percent. Relapse usually occurs within 1 to 6 weeks. Rarely, second or even third relapse may also occur. 
- HEMATOLOGY: Blood counts usually show a normal or low leucocyte count. There is always a moderate neutropenia leading to relative lymphocytosis. Thrombocytopenia and proteinuria may be observed.
- CULTURES: the blood culture during the first week shows Salmonella Typhi in over 75% of patients. The proportion of those with bacteremi declines in subsequent weeks. Bone marrow cultures are highly sensitive (90%) for diagnosis of typhoid fever. 
- SEROLOGY: The Widal agglutination test measures antibodies against the somatic (O) antigen, and the flagellar (H) antigens of salmonellae. These antibodies are usually detectable only by the end of first week of illness, and rise progressively during the course of illness. Widal test is said to be positive, if antibody titer to “O” antigen is >1:160 after 7 days of onset of illness; or it demonstrates a 4-fold rise between the paired sera, collected in the first week, and then at least 2 weeks later. Widal test is of no diagnostic utility on a single sample, if obtained in first week of illness or in areas of endemicity. The somatic antigen O is common for both typhi and paratyphi, while H antigen is specific for S. Typhi, paratyphi A, and paratyphi B. 
CAUSES OF FALSE POSITIVE AND FALSE NEGATIVE WIDAL REACTIONS:
- FALSE POSITIVES: Sub clinical infections or past clinical infection, typhoid vaccination, healthy carriers of Salmonella Typhi (generally adults).
- FALSE NEGATIVES: Too early in infection (widal becomes positive in 2nd week), Antibiotics early in the course of the disease will blunt antibody response. This is because typhoid is cured by cell mediated immunity and not by antibodies. 
Typhoid fever is a wholly preventable disease, as has clearly been demonstrated in Western countries. All typhoid cases should ideally be isolated in wards and discharged only after three consecutive stool and urine cultures are reported as sterile. Use of the typhoid vaccine for children in endemic areas confers a high degree of immunity. The choice of vaccine depends on the age at which the vaccine is given and the availability. Three different types of vaccines are available for use:
Whole cell vaccine: The heat-killed, phenol-preserved, acetone killed, lyophilised, whole-cell Salmonella typhi vaccine was developed a century ago. This vaccine is not in use in many countries because of the local pain and inflammation and systemic malaise and fever it induces in a large proportion of cases. Infants 6-9 months upwards respond to the vaccine with excellent antibody production. The dose for children may vary slightly among manufacturers to manufacturer, some recommending 0.25 ml and others 0.5 ml.
The primary course requires two doses, four or more weeks apart, given subcutaneously. For the booster dose, 0.1 ml given intradermally is as effective as the full dose (0.5 ml) given SC and causes significantly less local and systemic side effects. Though this vaccine is not presently available in the market, the Government of India, based on the recommendations of various experts including the IAP, have taken steps to manufacture a less reactogenic whole cell vaccine in India.
Vi polysaccharide vaccine: The Vi polysaccharide, purified and adjuvanted, is another satisfactory typhoid vaccine with reasonable efficacy and low reactogenicity. As polysaccharide antigens are T-cell independent, this vaccine is non-immunogenic at <2 years of age, induces IgM response without IgG response, cannot induce immunological memory and hence cannot induce a booster effect. When a dose is repeated 3-5 years later, it induces a response similar to that of the first dose. The vaccine efficacy is 70-80% and should be repeated every 2-3 years.
Oral Ty21a vaccine: The live attenuated strain of S typhi, namely Ty21a, is genetically stable and does not revert to virulence. The age of immunisation is 6 years and above, partly since the capsules are large and not well tolerated by preschool children and partly because of lack of sufficient data in younger children. The vaccine is to be given in three sittings, on alternate days. The entire course comprises one dose of immunisation. The protective efficacy is with 67-82% and should be repeated once in 3-5 years.
Apart from vaccines, boiling drinking water and milk and preventing children from buying contaminated sweets will go a long way in controlling the disease. Public health measures, including tracing of carriers and control of spread, play a vital role. 
- Intestinal hemorrhage may be suspected in the presence of dark stools or fresh blood in stool.
- Tender distension of abdomen, vomiting and other signs of peritonitis indicate perforation. Perforation is generally pinpoint and multiple so that surgical management is not always feasible.
- Toxic myocarditis may manifest as arrhythmias and ST- T changes in EKG. Even the relative bradycardia (heart rate less than the expected for the fever) occasionally seen in typhoid fever may be a manifestation of myocarditis. 
- Complications occur in about 25- 30% of untreated cases; the most serious complications are gastrointestinal hemorrhage, perforation, peritonitis, bacterial pneumonia, encelopathy, septic arthritis and urinary tract infections. These complications decrese with early diagnosis and treatment.
- THE CARRIER STATES: Typhoid fever convalescents usually cease to excrete he bacilli in their urine or stools within a month of the illness. However, some may continue to do so upto six months. These are known as convalescent carriers. Chronic carriers are those who harbor the bacilli, which remain active for years in their gall bladder or kidneys. They excrete the organisms periodically, thereby posing a continuous problem to society. 
- The prognosis for a patient with enteric fever depends on the rapidity of diagnosis and institution of appropriate antibiotic therapy.
- Other factors are the patient’s age, general state of health, and nutrition, the causative Salmonella serotype, and the appearance of complications.
- Infants and children with underlying malnutrition and patients infected with multidrug- resistant are at higher risk for adverse outcomes.
- Despite appropriate therapy, 2- 4% of infected children may experience relapse after initial clinical response to treatment.
- Individuals who excrete Salmonella Typhi for 3 mo or longer after infection are regarded as chronic carriers.
- The risk for becoming a carrier is low in children (<2% for all infected children) and increases with age.
- A chronic urinary carrier state can develop in children with schistosomiasis. 
REVIEW OF HOMOEOPATHIC LITERATURE
- Continued fever
- Fever gradually increases.
- Continued fever with swelled parotid and sensitive bones
- Paroxysms increasing in severity 
J H CLARKE
RUBRIC: Enteric Fever
- , Ars., Bap., Bol., Bry., Ech. a., Ham., Hyo., Iod., Iof., Ipo., Lach., Mr. o., Mr. cy., Mu. a., Ph. x., Pho., Pyro., Rhs., Ter. 
RUBRIC: Typhoid fever
- , Agar., ail., ant-t., apis., arn. Ars., arum-t., Bapt., bapt-c., ben., berb-a., Bry., calad., calc., calc-ar., canth. caps. carb-ac. Colch., dor., dulc., echi., eucal., ferr-m., hell., kali-c., lob-p., Lyc., manc., mosch., Mur-ac., naphtin., Nit-ac., nuph., Ph-ac., phenac., Phos., Rhus-t. Sec., septi., sol-ni., sul-h., Sulph., sumb., tarax., verat., veral-v. 
RUBRIC: TYPHOID, fever, salmonella
- acet-ac., achy., acon., aeth., agar., ail., alum., alumn., am-c., ant-c., ant-t., anthr., apis., arg., arg-n., arn., ARS., ars-s-f., ARUM-T., asar., atro., BAPT., bell., bor., BRY., cadm-s., calad., calc., camph., cann-i., , caps., carb-ac., carb-an., CARB-V., caust., cham., chel., CHIN., chin-ar., chin-s., CHLOR., cic.. cimic., cina, cocc., COLCH., con., CROT-H.. cupr., cupr-ar., cyt-l., dig., dor., dulc., ECHI., elaps, eucal, eup-a, eup-per., euphr., ferr.. ferr-m., ferr-p., GELS., glon., graph., gymn., haem., ham., hell., hep., hydr., hydr-ac.. hydrin-s, HYOS., ign., iod., ip., iris, kali-bi., kali-c., kali-m., kali-n., kali-p., kreos., LACH., lachn., laur., lept., lyc., lycps., maland., mang.. MERC., merc-c., merc-cy., merc-i-r., methyl., mez., mill., mosch., MUR-AC., nat-m., nat-s., nit-ac., nux-m., nar-v., oci-s., op., par., petr., ph-ac., PHOS., plan., plb., psor., puls., pyrog., rheum, rhus-g., RHUS-T., rhus-v., sang, sars., sec., sel., seneg., sep., sil, spig., stann., staph., STRAM., stry, sul-ac., SULPH., sumb., tarax.. tarent., ter., thuj., trio, tub., urt-u., vac., valer., verat., veral-v., xan, xero, zinc. 
- ACETIC ACID: Fever with violent delirium, incoherent talking, with distended abdomen and obstinate constipation or with rumbling of bowels, colic and diarrhea, followed by stupor, interrupted by delirious talking: slow, putrid fever with night-sweats. Intense thirst for water with passing large quantities of urine; vomiting of all nourishment with sensation as if there were a sore spot or ulcer in stomach; profuse, very weakening diarhoea in later stages of fever: febrile heat with dry, hot skin and oppressed breathing during first stage; great debility and prostration.
- AMMONIUM CARB: Adynamia; high-colored and foetid urine; glandular swellings, bleeding from nose, gums and bowels; sense of oppressive fulness in head, as if brain wanted to burst through, debility with soreness of whole body, has to lie down; great chilliness with the headache; hæmorrhagic diathesis from fluidity of blood and dissolution of the red blood-corpuscles: tendency to decubitus and gangrenous ulcerations.
- APIS MELLIFICA: Muttering delicium; trembling tongue, which is blistered, can hardly protrude it, dry, cracked or ulcerated: muscles relaxed so that patient slides down in bed: nervous, restless and fidgety; sleepy, but cannot sleep, shrill series, finally stupor as deep as under Opium, but happy, strange expression of face during muttering delirium; great soreness and bloatedness of abdomen; head and whole surface of body hot and dry; skin burning hot in some places and unnaturally cool in others; skin mostly dry or only transient sweat; bruised, sore feeling of skin; face puffed and dark-red, lips dry, covered with a brown crust; tongue feels as wooden studded around the edges with Misters and catches between teeth; prickling sensation in tongue and fauces and very tenacious, tough mucus in throat: anorexia, but much thirst: considerable swelling of spleen, abdomen sunken in, en pressing ileo-caecal region gargling as from fluid; great soreness and bloatedness of abdomen, so that the walls become tense: watery, foul-smelling diarrhea or constipation; incontinence of urine: moist cough, but can raise sputa only to the tongue, whence it must be wiped away; pulse weak, full and soft; roseola well developed.
- ARNICA: At an early stage diarrhoea of offensive gushing stools and apathy and stupefaction, with foul-smelling breath and ecchymotic black or yellowish-green spots on skin; weakness, weariness and bruised sensation, general sinking of vitality, compelling the patient to lie down, and still he asserts that he feels perfectly well; forgets the words while speaking and goes to sleep while answering questions; desires constantly, an account of general soreness, to move or to be moved about, as everything upon which he lies seems too hard; irritable and angry, wants to be let alone; fear of being touched; brown streak through middle of tongue: restlessness attending the soreness of abdomen; involuntary stool and urine, brown or white diarrhoea, with distention of abdomen before and rumbling in abdomen during stool; sore, bruised feeling in walls of chest and cough with expectoration of mucus and blood; load blowing inspirations and expirations, head hot, rest of cool, or at least not hot; head confused and cloudy, sitting as if in thought, yet thinks of nothing, like a waking dream; sleep unrefreshing and full of dreams, with whimpering and loud talking during sleep: stupor and petechiae.
- ARSENICUM: Must not be given too early and it follows Rhus. Restlessness and anxiety, with fear of death, from the start to the end; extreme restlessness with extreme exhaustion, patient thinks himself still able to move, but when he tries, finds out how weak he is, and may faint away with cold sweat all over; picking at bedclothes; delirium, fever and anxiety < about and after midnight; face distorted, sunken, anxious, Hippocratic; burning heat, as if hot water were flowing through the veins, with throbbing in head and desire to throw off covering; excessive thirst and drinks large quantities more frequently than mere sipping of fluid at a time; craves hot drinks; fluids roll audibly down the stomach; intellect enfeebled, but coma rare: eyes staring, glistening or sunken, dull, watery. or closed with sticky matter; hard hearing; lips dry, cracked; lips, gums and teeth covered with black sordes; tongue red, cracked or black and stiff; hence speaks unintelligibly; papillae raised around dorsum and tip of tongue; aphthae in mouth bleed readily; vomiting and retching; burn ing in stomach and bowels, sensitive to pressure; swollen abdomen full, but soft (Chin., hard, meteoristic), and from the decomposition of the fluids the flatus are putrid and offensive and the diarrhoeic stools scanty, brownish, watery, foul as from rotten ulcers, < from food and drink, after midnight, containing blood, mucus or pus; haemorrhages from different orifices; pulse weak, rapid or filiform and intermittent; breathing short and anxious; oppressed, rattling, dry cough; foetid breath, white miliary eruption, even petechiae; cold, clammy perspiration or hot, pungent, dry skin (calor mordax): restless and disturbed sleep, anxious and frightful dreams, at 3 A. M. on account of great heat; decubitus; general and rapid sinking of life’s forces and excessive prostration. Erethistic typhoid fever, follows well after Rhus, and many authors raise their voices against giving it too early, considering it more indicated in the second and third week.
- ARUM TRIPH: During delirium boring in nose, picking at one spot or at the dry lips: quivering of upper lids; picking ends of fingers and dry lips till they bleed; restless tossing about the bed, wants to escape; unconscious of what he is doing or of what is said to him; urine suppressed; putrid odor from mouth; buccal cavity raw and bleeding; diarrhoea dark yellow, fluid or mushy, each succeeding discharge more watery; sleepy, but on falling asleep sensation of smothering: great weakness; last stage, probably with uraemic poisoning.
- BAPTISIA: First stage of typhoid or septic fevers with predominance of nervous symptoms; face flushed, dusky-red or hot with a besotted expression, dullness and confusion of mind; chilliness and soreness of body with intolerance of pressure on lying; chilly all day and hot at night: nightly deliria with stupor, heavy sleep with frightful dreams; dark sordes on lips and teeth; tongue dry and brown down centre; pulse full and rapid, but soft and easily compressed; high temperature: restless, tossing about the bed with the illusion that he is double, or that he is scattered about and tries to get himself together again, or sensation as if his upper or lower extremities were enormously enlarged; slight sensitiveness in ileo-ceacal region and yellow, putrescent stools. During second or third week prostration profound, stupor, patient falls asleep while answering questions; heavy, dark, besotted look of face; aphthae in mouth; all exhalations and discharges exceedingly offensive; stools horribly putrid; urine and sweat offensive. Blood is decomposed from high temperature and sepsis.
- BELLADONNA: In the beginning, during the stage of irritation by the typhoid poison, furious delirium with screaming out and violent efforts to cape from the bed and house; face more often bright than deep red: escape pupils dilated, eyes injected; full of fear; intense headache, with lancinations in back part or top of head; vertigo with staggering on on attempting to walk; frightful visions and dreams disturb sleep; heavy, snoring sleep with jerking of muscles, twitching of limbs and screaming out; tongue red, hot, dry, papilla inflamed and much swollen; speech difficult and stammering: reddish spots like flea-bites on chest, abdomen, face and neck; constipation profuse diarrhoea; urine scanty, with or without sediment; sense of weariness and heaviness in limbs, with marked debility and weakness; cold feet.
- BRYONIA: In early stages confusion of mind and mild delirium, on closing eyes for sleep he sees persons who are not present, but rectifies his mistake when opening them; delirium at night of the business of the day; desire to get out of bed and go home; sensation in bed as if sinking down and in the morning dizziness, as if the head were whirling in a circle; splitting headache and sensation of weight pressing on vertex, > in rest and from external pressure; dryness of lips and tongue, with thirst, drinking much at a time but not often; accumulation of frothy, soap like saliva in mouth and throat, sometimes nearly choking the patient; constant nausea; tongue coated more in middle; gastric affections; rumbling and gurgling in abdomen, especially inguinal region; constipation (Bapt. has early diarrhoea); pulmonary congestion, with dry, irritative cough, stitching pains in chests pressure as of a weight in middle of sternum, with anxious and difficult breathing. During second or third week stupor, frontal headache, face flushed, of a deep red color, <by motion, > by nosebleed, usually towards morning; dryness of mucous membranes, but drinking causes nausea and vomiting, with sensation of heavy pressure in stomach, as if a stone were there; great lassitude and weakness; wants to be quiet; pains in all limbs when moving; tongue dry, rough, cracked, dark brown: sighing, groaning, moaning, makes motions with his hands, it is too much exertion to talk; constipation or diarrhoea, sudden and almost involuntary discharges, very offensive, every three hours: involuntary defecation and urination; peculiar sour smell of body, with or without sweat; heat intense and almost continuous; wants to sleep all the time; coma with anxious delirium, cold sweat on forehead, followed by weakness; suffocating snoring with the inspiration; somnolence during day, agitated at night; disposition subdued, but easily excited to anger.
- CALCAREA CARB: At the very onset, in children or in persons inclined to grow fat, after great anxiety and worriment of mind: utter sleeplessness from overactivity of mind, where the same disagreeable ilea always rouses the patient as often as he falls into a slight slumber: visions of faces and persons when eyes are closed, sees and plays with cats and dogs during delirium; constant tickling under muddle of sternum, causing a hacking cough, <from talking or moving: during coughing painful shocks in head, the brain feeling hot and burning, but circulation deficient in extremities; rash fails to appear. Or during second or third stage excessive diarrhoea with intestinal ulceration; palpitation, tremulous pulse; anxiety, sleeplessness and restlessness; redness of face, delirium; jerkings, especially in children; great weakness and exhaustion, chiefly in the morning. Easy relapses, one does not continue to convalesce. It brings out the miliary rash, the meteorism and sensitiveness of abdomen diminish, and with it the anxiety and agitation; stools less frequent and more consistent.
- CARBO VEG: Our last resort in critical cases, inclining to dissolution. Extreme collapse, sopor, rattling, cold sweat; hippocratic face; small, filiform pulse; tongue moist, sticky, forepart cracked, heavy and scarcely movable; eyes dull and sunken, no reaction of pupils to light; face and lips partially cyanosed; haemorrhages from mouth and nose: bloody foetid stools; abdomen distended, with copious escape of putrid flatus; heart’s action fails rapidly, congestion of lungs sets in with threatening pulmonary paralysis; breath cold and loud rattling breathing from the start; bedsores and ecchymoses from decomposition of the blood; stupor, from which the patient can only be roused for a moment, with loss of vision and meaning; internal burning up with icy coldness of feet and legs up to knees. Such a collapse sets in sometimes early with perfect asthenia in typhoid fevers of drunkards, who complain of itching of skin day and night; they want to be fanned and must have windows open to inhale the fresh air.
- CHINA: Typho-malarial fever; excessive prostration, with great mental and bodily weakness, so that the least exertion is hateful; heavy sweats during motion or in sleep, with excessive sinking of the vital forces; uneasiness and sleepiness; frightful fancies on closing the eyes to sleep; vertigo and heaviness of head, dimness of sight, dullness of hearing, pale face, dry mouth, yellow-coated tongue, with slimy, bitter taste and great thirst: abdomen meteoristic and tender with pains in bowels, watery henteric stools, scanty urine; bowels move in daytime only after nourishment, but at night frequent, dark, fluid diarrhoea; coldness, especially of hands and feet; breathing oppressed, especially in the evening: swelling and hardness of spleen; tardy convalescence in consequence of serious hemorrhages, exhausting diarrhoea and night-sweats, with progressive loss of flesh and strength; indifference and apathy.
- EUPATORIUM PERF: Bilious and remittent malarial fever, with severe gastric and intestinal irritation, passing over into typhoid state. Despondency with the fever; throbbing headache, from forehead to occiput; soreness and pulsation in back part of head; sickly, sallow face; tongue yellow or covered with white fur; copious perspiration with nausea and vomiting; frequent heat with the night-sweat; alternate chilliness and flushes of heat, fullness and tenderness in hepatic region; profuse bilious, watery stools, with nausea, severe colic and prostration or constipation; bones ache as if broken, with much backache and headache; jaundice; petechiae.
- GELSEMIUM: Great prostration of all the vital forces already in the initial stage, with strange sensation in head and continued jacitation of muscles; sleeplessness, wide awake all night; patient feels sore and bruised all over, as if he had been pounded, dreads to move, on account of weakness; suffused red face; trembling from weakness; slow pulse, which becomes accelerated by lifting or turning the patient; chills and crawls which go down the back; feeling of expansion, as though the head or some part of the body were enormously enlarged; severe pains in head, back and limbs, with extreme lassitude, chilliness and fever (afternoon); sticky, clammy, feverish state; tongue red and raw, painful in centre, can hardly protrude it; distention of abdomen, with pain and nausea; diarrhea, bilious, fermented, with much flatus and great nervous weakness, more than the stools could cause. Post- typhoid intermittents.
- RHUS TOX: Whenever an acute disease takes on a typhoid form. Mild temperament. Excitement and overactivity in the functions of vegetative life, and simultaneous depression in functions of animal life; desire for fre quent and constant movement, giving temporary relief; prostration with sensation as if bruised, and constant desire to sit or lie down; dull feeling of head, with cerebral pains, > by nosebleed; dry, burning heat, excessive headache, with tension and rigidity of nape of neck, < evenings and upon motion: wandering pains in nape of neck and kidneys, with weariness and languor of limbs at the most acute stage of first period, when the nervous symptoms begin to manifest themselves, when tongue is coated with fur and there is diarrhoea with borborygmi; chills, vertigo, with closing of eyelids, altered color of face, dryness of throat, vomiting of food, yawning: hard, dull and heavy pressure upon eyes, painful sensitiveness to light and noise; somnolence; loss of memory; tendency to mild delirium; lower lip and tongue blackish. During second and third stage sopor and prostration pre vail, with extreme weariness, preventing the least motion; slow and difficult mental operation, answers correctly, but slow, sometimes hasty; talks much to himself incoherently; epistaxis, especially after midnight; lips dry and covered with brown crusts; sensation of dryness on tongue, as if covered with a skin, when not dry; dry tongue, red all over, at any rate dry red triangle on tip, with desire for drink; aldomen, with severe pinching very of Pugnance to all food: distection of flatus: bowels loose, worse at night, and involuntary during sleep; nocturnal diarrhea, with severe celi which disappears after stool, with headache and pain in all limba; severe celic, cough, with tough bloody expectoration; bronchitis; pneumonic infiltration of lower lobes of lungs; severe rheumatic pains in limbs, worse when at rest: restlessness; disturbed, anxious sleep, with frightful dreams, frequent waking, or comatose slumbering, with snoring, murmuring, picking at bed clothes; dry heat or sweat, during which patient desires to be covered; brain seriously affected, with automatic muscular movements in hands and feet; roseola; miliary eruption; great exhaustion; disposition sad, depressed, without courage, despairing, but never violent. Cases adapted to Rhus never run a speedy course, and a crisis can only be expected during the third week; the medicine ought to be steadily adhered to without change, except when imperatively commanded. 
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