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Health Diseases: a Main Signs of Fever

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Salmonella enterica typhi is a human restricted pathogen and paratyphoid are host adapted. The risk of paratyphoid fever transmission by food and water is low. The use of human faeces for farming was causing the contamination of vegetables and fruits. This source of contamination is the most commonly described is several settings. The pathogen doesn’t multiply in water. The potential infective dose of typhoid fever is 109 while it is much higher for paratyphoid fevers.

Factors facilitating the infections occurrence include gastric acidity, the possession of Vi antigen by the pathogen and the number of pathogens ingested. An estimate of 10 9 pathogens induce infection in 95% of cases in healthy populations (Cook;, 2009).

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A specific biological feature of S.typhi in specific medium (Kliger ion agar) is the formation of an alkaline slant, H2S and acid without gas. It is a non-lactose fermenting bacterium. Serological identification and demonstration of the lipopolysaccharide antigen O9, 12 (group D), protein flagellar antigen Hd and Vi polysaccharide capsular antigen are keys elements for its confirmation(Parry, 2006).

Diagnosis

Clinical diagnosis

Most cases are asymptomatic or mild and treated as outpatients. The initial clinical presentation is fever without localizing sign. Incubation period is ten days but can ranged from 7 to 21 days for typhoid fever and 1 to 10 days for paratyphoid fevers. The clinical features are changing over time.

During the first week, an increasing fever associated with mild headaches and malaises are the most predominant symptoms. Sometimes, non-productive cough and constipation are observed.

The second week is dominated to primary toxaemia and plateaued temperature. Abdominal symptoms are common at this stage. Specifically, half of patients present popular lesions on the lower chest and upper abdominal part.

Sustained fever and confusion as well as persistent abdominal signs are predominant during the third and fourth weeks. Most of the severe complications occurs at this stage. After the fourth week, the patient recovers progressively. Untreated, 10% of cases die from overwhelming toxaemia (Cook;, 2009).

Biological diagnostic

The gold standard for enteric fever diagnosis is bone marrow culture or blood culture with the first being more sensitive but less practical and is invasive. The pathogens are isolated in 90% of cases from bone marrow culture.

Several serological tests are used for the diagnosis but their sensitivity and specificity are very low. The most common test used in the Felix-Widal agglutination test. This test uses somatic “O” and flagellar “H” antigen isolated from S. typhi and Paratyphi A & B to detect the corresponding antibodies in the serum respectively IgM somatic O antibody (acute phase) and IgG flagellar antibody (progressively rise and persistent)(Olopoenia and King, 2000). The sensibility and the specificity of Widal test are respectively varies across regions. In Nepal, for TH the sensitivity and specificity were 45.22% (41.27-49.17) and 82.32 % (79.9-87.82) respectively while those of TO were 43.45 and 82.31%. In this endemic country, the low sensitivity is a major drawback for its reliability(Adhikari et al., 2015). In addition, the cross reaction with S.paratyphi A, B as well as malaria, chronic hepatitis are also major limitations.

Others rapid diagnosis tests (Typhidot,) are used in developed settings but their benefit have not been demonstrated in endemic settings. There is a strong need of a more specific and sensitive rapid diagnosis test for typhoid fever (Wijedoru et al., 2017).

Complications

The major complications of enteric fever are intestinal perforation and intestinal bleeding. These complications may be the first clinical presentations as they can occur regardless of the severity of the diseases. Repeated bleedings are observed at the earliest stage. During the third week, both perforation and massive haemorrhage. A haemolytic anaemia is common in these cases.

Therapeutic aspects

The emergence of multidrug resistant (MDR) Salmonella spp become an important challenge for the treatment. MDR rates are increasing worldwide and specially in South-East Asia with the presence of H58 strain which is driving mainly the resistances. The mainstay treatment was fluoroquinolones in several settings before the emergence of resistances to these drugs two decades ago. Azithromycin use is increasing in endemic regions specially for children and MDR patients. Most of strains remains sensitive to cephalosporin and imipenem(Wain et al., 2015).

There is a regain of sensibility to first line antibiotic in several South Asian countries raising the potential to revised the current diseases clinical management strategy.

Prevention

The main preventive method of enteric fever remains improved sanitation, access to safer food and water. These conditions provision in developing countries is a great challenge due to the increasing poverty, non-sustainability of WASH activities and lack of resources.

There are currently three licensed vaccines of typhoid fever vaccines were licensed: the oral Ty21a vaccine, the Vi polysaccharide vaccine and the conjugate vaccine. Both vaccines are protective against S. typhi only.

The oral live attenuated, Ty21a vaccine is a heat labile vaccine in capsules. It is a 3 doses regimen vaccine. It is not suitable for use in public health interventions as the cold chain is often not available. The vaccine is recommended for 6 years old children.

The Vi polysaccharide vaccine is a single dose intra-muscular vaccine licensed in 1992. The vaccine was recommended by WHO for use in countries with high endemicity (typhoid fever incidence > 100 cases/ 100,000 habitants) (WHO., 2012). Protection starts one week after administration and reach its peak four weeks later (Garmory et al., 2002). Vi PS is recommended for subjects aged more than 2 years children. It is a T cell independent vaccine implying the short protection, need of revaccination and moderate immunogenicity(Scobie et al., 2014). The vaccine is well tolerated and did not induce severe adverse events. It hasn’t cross protection again paratyphoid and no booster effect (Date et al., 2015).

The conjugate vaccine, the newly licensed vaccine, is a single dose Vi antigen-based vaccine combined with tetanic toxoid. As the Vi PS is only It has the advantage to be more immunogenic and can be administrated at younger age (from 6 months). It’s protective during duration is 3 years but current studies suggest much longer protection(Date et al., 2015). This vaccine is considered for introduction in routine immunisation program in high endemic countries with Global Alliance for Vaccines and immunization (GAVI)(World Health, 2018).

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