TYPHOID AND MALARIA

1. TYPHOID
By Dr.M.A.Ansari

2. INTRODUCTION
•The term enteric fever is used to describe acute
infection caused by Salmonella typhi (typhoid
fever) or Salmonella para typhi (paratyphoid
fever).

3. A ultra microscopic
image of S.typhi

4. PATHOGENESIS
• Route of entry- The typhoid bacilli are ingested through contaminated
food or water.
• During the initial asymptomatic(no symptoms as such) incubation
period of about 2 weeks, the bacilli invade the lymphoid follicles and
Peyer’s patches of the small intestine and proliferate.
• Following this, the bacilli invade the blood- stream causing
bacteraemia and the characteristic clinical features of the disease like
continuous rise in temperature and ‘rose spots’ on the skin are
observed.

5. • All 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 propria.
• Nontyphoidal 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.

6. Lamina propria location

7. • In contrast to the nontyphoidal 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
common paratyphi S, paratyphi A, does not. This explains the
greater infectivity of typhi compared with most of its cousins.

8. • Immunological reactions (Widal’s test) begin after about 10 days and
peak titres(concentration of antibody) are seen by the end of the third
week.
• Eventually, the bacilli are localised in the intestinal lymphoid tissue
(producing typhoid intestinal lesions), in the mesenteric lymph nodes
(leading to haemorrhagic lymphadenitis), in the liver (causing foci of
parenchymal necrosis), in the gallbladder (producing typhoid
cholecystitis), and in the spleen (resulting in splenic reactive
hyperplasia).

9. MALARIA

10. Introduction
• Malaria is a protozoal disease caused by any one or
combination of four species of plasmodia:
Plasmodium vivax, Plasmodium falciparum, Plasmodium
ovale and Plasmodium malariae.
While Plasmodium falciparum causes malignant malaria, the
other three species produce benign form of illness.
• The disease is endemic in several parts of the world,
especially in tropical Africa, parts of South and Central
America, India and SouthEast Asia.

11. Microscopic image of
P.falciparum among RBCs

12. PATHOGENESIS
•Malaria infection develops via two phases: one that
involves the liver (exoerythrocytic phase), and one that
involves red blood cells, or erythrocytes (erythrocytic
phase).
•When an infected mosquito pierces a person's skin to
take a blood meal, sporozoites in the mosquito's saliva
enter the bloodstream and migrate to the liver where
they infect hepatocytes, multiplying asexually and
asymptomatically for a period of 8–30 days.

13. • After a potential dormant period in the liver, these
organisms differentiate to yield thousands of merozoites,
which, following rupture of their host cells, escape into the
blood and infect red blood cells to begin the erythrocytic
stage of the life cycle. The parasite escapes from the liver
undetected by wrapping itself in the cell membrane of the
infected host liver cell.
• Within the red blood cells, the parasites multiply further,
again asexually, periodically breaking out of their host cells
to invade fresh red blood cells. Several such amplification
cycles occur. Thus, classical descriptions of waves of fever
arise from simultaneous waves of merozoites escaping and
infecting red blood cells.

14. • Some P. vivax sporozoites do not immediately develop into exoerythrocytic-phase
merozoites, but instead, produce hypnozoites that remain dormant for periods
ranging from several months (7–10 months is typical) to several years.
• After a period of dormancy, they reactivate and produce merozoites. Hypnozoites
are responsible for long incubation and late relapses in P. vivax infections.

15. • The parasite is relatively protected from attack by the
body's immune system because for most of its human life
cycle it resides within the liver and blood cells and is
relatively invisible to immune surveillance. However,
circulating infected blood cells are destroyed in the spleen.
• To avoid this fate, the P. falciparum parasite displays
adhesive proteins on the surface of the infected blood cells,
causing the blood cells to stick to the walls of small blood
vessels, thereby sequestering the parasite from passage
through the general circulation and the spleen. The blockage
of the microvasculature causes symptoms such as in placental
malaria.
• Infected red blood cells can breach the blood–brain
barrier and cause cerebral malaria.

16. PATHOLOGIC CHANGES
• Parasitisation and destruction of erythrocytes are responsible for major
pathologic changes
• Malarial pigment liberated by destroyed red cells accumulates in the
phagocytic cells of the reticuloendothelial system resulting in enlargement
of the spleen and liver (hepatosplenomegaly).
• In falciparum malaria, there is massive absorption of haemoglobin by the
renal tubules producing blackwater fever (haemo globinuric nephrosis).
• At autopsy, cerebral malaria is characterised by congestion and petechiae on
the white matter.
• Parasitised erythrocytes in falciparum malaria are sticky and get attached to
endothelial cells resulting in obstruction of capillaries of deep organs such
as of the brain leading to hypoxia and death.
• If the patient lives, microhaemorrhages and microinfarcts may be seen in
the brain. The diagnosis of malaria is made by demonstration of malarial
parasite in thin or thick blood films or sometimes in histologic sections

17. Life cycle of malarial parasite

18. CLINICAL FEATURES
• Major complications occur in severe falciparum malaria
which may have manifestations of
cerebral malaria (coma)
Hypoglycaemia
renal impairment
severe anaemia
haemoglobinuria, jaundice
pulmonary oedema
and acidosis followed by congestive heart failure and
hypotensive shock

19. DIAGNOSIS
•Malaria is usually confirmed by the microscopic
examination of blood films or by antigen-
based rapid diagnostic tests (RDT). In some
areas, RDTs need to be able to distinguish
whether the malaria symptoms are caused
by Plasmodium falciparum or by other species of
parasites