Hasanein Ghali, MD Department of Pediatrics College of Medicine – University of Baghdad December, 28th, 2015

1. Kala-Azar
Hasanein Ghali, MD
Department of Pediatrics
College of Medicine – University of Baghdad
December, 28th, 2015

2. Introduction
 Intracellular protozoan parasites of the genus Leishmania, which are
transmitted by phlebotomine sandflies.
 Multiple species of Leishmania are known to cause human disease
involving the skin and mucosal surfaces and the visceral
reticuloendothelial organs.
 Cutaneous disease is generally mild but may cause cosmetic
disfigurement.Visceral leishmaniasis is associated with significant
morbidity and mortality.
 Dimorphic, existing as :
a flagellate promastigote in
the insect vector.
Aflagellate amastigote, resides and replicates
only within the vertebrate host.

3. phlebotomine sandflies

4. Lifecycle
Infective
meatcyclic form
Non infective
procyclic form
• Resistant to the acidic, hostile environment of the macrophage and eventually
ruptures the cell and goes on to infect other macrophages.
• Infected macrophages have a diminished capacity to initiate and respond to an
inflammatory response, thus providing a safe haven for the parasite.

5. Epidemiology / Pathogenesis
• The leishmaniases may occur sporadically throughout an endemic
region or may occur in epidemic focuses.
• With only rare exceptions, the Leishmania organisms that primarily
cause cutaneous disease do not cause visceral disease.
• Cutaneous leishmaniasis is caused by L. major and L. tropica.
• Visceral leishmaniasis is caused by L. donovani and L. infantum.
• In VL there is prominent reticuloendothelial cell hyperplasia in the
liver, spleen, bone marrow, and lymph nodes.
• Individuals with prior active disease or subclinical infection are
usually immune to a subsequent clinical infection.

6. Epidemiology / Pathogenesis
• Within endemic areas, people who have had a subclinical infection can be
identified by a positive delayed-type hypersensitivity response to
leishmanial antigens.
• Subclinical infection occurs considerably more frequently than does active
cutaneous or visceral disease.
• Host factors (concomitant disease, nutritional status), parasite factors
(virulence, size of the inoculum), and possibly vector specific factors
(vector genotype) influence the expression as either subclinical infection
or active disease.
• Within endemic areas the prevalence of skin test result positivity
increases with age and the incidence of clinical disease decreases with age,
indicating that immunity is acquired in the population over time.

7. Clinical features
• kala-azar typically affects children less than 5 yr of age.
• After inoculation of the organism into the skin by the sandfly, the
child may have a completely ---->>>>
1- Asymptomatic infection : show no clinical evidence of disease. or
2- Oligosymptomatic illness that either resolve or goes into active form
• Mild constitutional symptoms (malaise, intermittent diarrhea, poor
activity tolerance) and intermittent fever.
• In most of these children the illness will resolve without therapy, but
in approximately 25% it will evolve to active kala-azar within 2-8
months.

8. 3- Active Kala-azar: The classic clinical features of
• High fever, marked splenomegaly, hepatomegaly, and severe cachexia.
• Typically develop approximately 6 months after the onset of the
illness, but a rapid clinical course over 1 month has been noted in up
to 20% of patients.
• At the terminal stages: hepatosplenomegaly is massive, gross wasting,
the pancytopenia is profound, and jaundice, edema, and ascites may
be present. Bleeding episodes, especially epistaxis, are frequent.
• The late stage of the illness is often complicated by secondary
bacterial infections, which frequently are the causes of death.
• Death occurs in >90% of patients without specific antileishmanial
treatment.
Clinical features (cont’d)

9. Clinical features (cont’d)
• VL may also result from reactivation of a long-standing subclinical
infection.
• A small percentage of patients previously treated for VL develop
diffuse skin lesions, a condition known as post–kala-azar dermal
leishmaniasis (PKDL). These lesions may appear during or shortly
after therapy or up to several years later.
• The lesions of PKDL are hypopigmented, erythematous, or nodular
and commonly involve the face and torso. They may persist for
several months or for many years.

13. Diagnosis
1- Non specific: Anemia, thrombocytopenia, leucopenia , elevated
hepatic transaminase levels, and hyperglobulinemia.
2- Specific: Serologic testing is very useful in VL because of the very
high level of antileishmanial antibodies (IFAT, ELISA, LAT). An
enzvme-linked immunosorbent assay using a recombinant antigen (K39)
has a sensitivity and specificity for VL that is close to 100%.
• A negative serologic test result in an immunocompetent individual is
strong evidence against a diagnosis of VL.

14. Diagnosis (cont’d)
3- Definitive diagnosis of leishmaniasis is established by the
demonstration of amastigotes in tissue specimens or isolation of
the organism by culture.
• In patients with VL, smears or cultures of material from splenic,
bone marrow, or lymph node aspirations are usually diagnostic.

16. Differential diagnosis
• prolonged fever,
• cachexia,
• marked splenomegaly,
• hepatomegaly,
• Cytopenias.
• malaria,
• typhoid fever,
• brucellosis,
• infectious mononucleosis,
• leukemia.

18. Treatment
• All patients with VL should receive therapy.
• The pentavalent antimony compounds (sodium stibogluconate-
Pentostam and meglumine antimoniate- Glucantime) have been the
mainstay of antileishmanial chemotherapy for >40 yr.
• The recommended regimen is 20 mg/kg/day intravenously or
intramuscularly for 28 days.
• An initial clinical response to therapy usually occurs in the 1st week of
therapy but Complete clinical healing is usually not evident for weeks to
a few months after completion of therapy.

19. Treatment (cont’d)
• Cure rates with this regimen of 80-100% for VL were common in the
1990s, but clinical resistance to antimony therapy has become common.
• Relapses are common in patients who do not have an effective
antileishmanial cellular immune response. These patients often require
multiple courses of therapy or a chronic suppressive regimen. When
clinical relapses occur, they are usually evident within 2 mo after
completion of therapy.
• Adverse effects of antimony therapy are dose and duration dependant:
Fatigue, arthralgia and myalgias, Abdominal discomfort, elevated
hepatic transaminase level, elevated amylase and lipase levels, Mild
hematologic changes.
• Sudden death due to cardiac toxicity is extremely rare and associated
with very high doses of antimony Rx.

20. Other therapies
1. Amphotericin B is very useful in the treatment of VL or ML, and in
some regions used as 1st line therapy.
2. Recombinant human interferon as an adjunct to antimony therapy in
the treatment of refractory cases of VL.
3. Miltefosine, a membrane-activating phospholipid, has been developed
as the 1st oral treatment for VL.
4. Paromomycin and Pentamidine.

22. Follow up
Clinical
1- General
condition
(1st week).
2- Body
temperature
(1st week).
3- Liver and spleen
size
(weeks to months).
Hematological
1- CBC
(weeks to months).
Serological
1- K39 assay
2- PCR

25. Black fever

26. Epstein Barr Virus

27. • EBV is a gamma-type herpesvirus .
• The two major strains of EBV (EBV type-1 and -2) differ biologically and
in their geographic and ethnic prevalences.
• Infectious mononucleosis is the best-known clinical syndrome caused by
Epstein-Barr virus (EBV), originally described as glandular fever.
• Other pathogens may cause a mononucleosis-like illness like CMV,
Toxoplasma, Hepatitis, Adenovirus and HIV.
• The age at first infection varies according to living conditions.
Introduction

28. • The virus is shed in the secretions (saliva and genital).
• The term “kissing disease” acknowledges the oral route by which most
people are infected.
• Infection occurs at an earlier age in the presence of poor hygiene and
crowded living conditions.
• EBV infects >95% of the world’s population. It is transmitted via
penetrative sexual intercourse and in oral secretions such as “deep
kissing” and sharing water bottles.
• It can also be transmitted by blood product transfusion and with bone
marrow and solid organ transplantation.
Introduction (cont’d)

29. • Among children, transmission may occur by exchange of saliva from child
to child, such as occurs between children in out-of-home child care.
• EBV is shed in oral secretions consistently for >6 mo after acute
infection and then intermittently for life.
• Primary EBV infection in adolescents and adults manifests in >50% of
cases as the classic triad fatigue, pharyngitis, and generalized
lymphadenopathy, which constitute the major clinical manifestations of
infectious mononucleosis.
• This syndrome may be seen at all ages but is rarely apparent in children
<4 yr of age, when most EBV infections are asymptomatic, or in adults >40
yr of age, of whom most individuals have already been infected by EBV.
Epidemiology

30. Clinical Aspects
Primary Infection
• Symptomatic acute EBV infection is recognized clinically as IM.
• The incubation period is 30-50 days. Shorter in children.
• The majority of cases of primary EBV infection in infants and young
children are clinically silent. In older patients, the onset of illness is
usually insidious and vague.
• Patients may complain of malaise, fatigue, acute or prolonged (>1 wk)
fever, headache, sore throat, nausea, abdominal pain, and myalgia.
This prodromal period may last 1-2 wk. The sore throat and fever
gradually worsen until patients seek medical care.

31. Primary Infection
• The pharyngitis can vary from a mild erythema to a very painful
throat that has a thick gray-white exudate. Petechiae at the
junction of the hard and soft palate are frequently seen.
• The classic physical examination findings are generalized
lymphadenopathy (90% of cases), splenomegaly (50% of cases),
and hepatomegaly (10% of cases).
• Lymphadenopathy occurs most commonly in the cervical nodes and
less commonly in the axillary and inguinal lymph nodes.
Epitrochlear lymphadenopathy is particularly suggestive of
infectious mononucleosis.

32. Clinical Aspects (cont’d)
• Splenomegaly to 2-3 cm below the costal margin is typical; massive
enlargement is uncommon.
• Fatigue: A distinct fatigue syndrome is associated with IM, lasting
about 8 weeks.
• Rash: Rashes are usually maculopapular and have been reported in 3-
15% of patients.
• Antibiotic administration, particularly of Ampicillin, has been linked
to the subsequent development of rash in older patients who have
IM (80%). This vasculitic rash is probably immune mediated and
resolves without specific treatment.

37. Other consequences
• X-linked Lymphoproliferative Disease .
• Burkitt Lymphoma .
• Nasopharyngeal Carcinoma .
• Hodgkin Disease .
• T-cell Lymphoma .
• Gastric Carcinoma

38. Diagnostic Tests
 Non specific tests:
• WBC: 10,000-20,000 cells/mm3, of which at least two thirds are
lymphocytes; atypical lymphocytes usually account for 20-40% of the
total number.
• Atypical lymphocytosis in acquired cytomegalovirus, toxoplasmosis,
hepatitis, rubella, roseola, mumps, tuberculosis, typhoid, Mycoplasma,
malaria, and drug reactions.
• PLT: 50,000-200,000 platelets/mm3 but only rarely is associated with
purpura.
• Mild elevation of hepatic transaminase values occurs in approximately
50% of uncomplicated cases but is usually asymptomatic and not
associated with jaundice

40. Diagnostic Tests (cont’d)
 Specific tests:
Epstein-Barr virus (EBV) infection induces specific antibodies to EBV
and various unrelated non-EBV heterophile antibodies.
1. Specific Antibodies: VCA (IgM early and IgG late) and EBNA (late).
2. Heterophile Antibodies: These antibodies react to antigens from
animal RBCs.
• Culture of EBV is tedious and requires 4-6 wk.
‫ممل‬

44. Diagnostic Tests (cont’d)
• Documenting the presence of heterophile antibody virtually
confirms acute EBV infection, and there usually is no reason for
further diagnostic tests.
• A positive heterophile reaction is a desirable adjunct but not
essential to the diagnosis
• Sheep RBCs agglutinate with heterophile antibodies: Paul-Bunnell
test. Positive for months
• Horse RBCs on exposure to heterophile antibodies: Monospot test.
Positive for up to 2 yrs. It detects 90% of cases in older children
but in only up to 50% of cases in children <4 yr of age because of
lower titer.

45. Complications
• Occur in about 20% of patients recently infected with EBV;
• Essentially no body system is free from potential harm. The
respiratory, neurologic, and hematologic systems are involved most
frequently.
• Airway obstruction can be life threatening and is the most common
reason for hospital admission.
• EBV has been implicated in virtually every form of infection-related
neurologic disorder.

46. Complications (cont’d)
• Auto reactive antibodies cause immune hemolytic anemia or immune
thrombocytopenia. About 10% of preschool age children develop
neutropenia.
• Generally, increased levels of Ig increase the propensity for
immune complexes to be formed, which may account for other
disease-associated features such as rash, myalgia, and arthralgia.
• Rare complications: pancreatitis, orchitis and parotitis.

47. Treatment
 Resources to manage acute EBV infection and its complications
remain limited.
 “Take it easy” is a usual recommendation.
 Contact sports and activities (i.e., bike riding)? Spleen?
 Although steroids often are recommended for management of
impending (1) airway obstruction or (2) severe thrombocytopenia,
only anecdotal evidence supports their benefit.

48. Prognosis
• The prognosis for complete recovery is excellent. The major
symptoms typically last 2-4 wk followed by gradual recovery.
• Prolonged and debilitating fatigue, malaise, and some disability that
may wax and wane for several weeks to 6 mo are common
complaints even in otherwise unremarkable cases.
• Occasional persistence of fatigue for a few years is well
recognized.

49. Exudative Tonsillitis

52. Ampicillin rash

59. Thank you
Live in peace, not in pieces