Lecture 8: Leishmaniasis and neglected tropical diseases

Question 1

What can be done for control of leishmaniasis?

Answer 1

•Early detection and treatment
o Active case finding and access to free diagnostic and treatment services
•Control of the reservoir hosts
o In the Mediterranean and the Americas there is zoonotic transmission of leishmania infantum
•Vector control
o In East Africa and South India, Leishmania donovani is transmitted by sand flies from human to human
o Insecticide spray
o Environmental control
•Epidemic response
•Vaccination

Question 2

What is the incidence and mortality of Visceral leishmaniasis/black fever/kalahazar?

Answer 2

Visceral leishmaniasis/black fever/kalahazar:
•Incidence: 50,000-90,000 cases per year in 80 different countries. 90% of cases are found in East Africa, India and Brazil.
•Mortality: 10,000-20,000
•Many patients don’t have access to treatment

Question 3

How is leishmaniasis caused in East Africa and South India?

Answer 3

In East Africa and South India, Leishmania donovani causes visceral leishmaniasis. It is transmitted by sand flies from human to human.

Question 4

What is Visceral leishmaniasis/black fever/kalahazar?

Answer 4

•It is a systemic disease of the viscera (ingewanden) which causes immune suppression
•Symptoms are: 
o	Fever
o	Weight loss
o	Weakness
o	Diarrhoea 
o	Hepato- and splenomegaly
o	Pancytopenia 
o	Spontaneous bleeding
o	Abdominal pain
o	Anaemia 
o	Opportunistic infections due to immune suppression
•Fatal if not treated

Question 5

What is the case definition of visceral leishmaniasis/black fever/kalahazar?

Answer 5

Fever for more than two weeks and splenomegaly

Question 6

What happens to a patient with suspected leishmaniasis?

Answer 6

They get tested with a rapid-diagnostic test. It is a very simple test with results within 15-20 minutes. If it’s negative leishmaniasis can be excluded. If it is positive leishmaniasis is confirmed and treatment is started.

Question 7

What is the difference in testing in Africa?

Answer 7

In Africa, this rapid-diagnostic test only has a sensitivity of 85-90%, meaning you miss 10-15% of your patients for a FATAL disease. To find those patients, you need an additional diagnostic algorithm. If the rapid-diagnostic test is negative, you can do a quantitative serological test. With low titres, you can exclude kalahazar and with high titres disease is confirmed. However, there is the possibility of intermediate/borderline titres where you don’t know. In this case, you need to do biopsies of the spleen or lymph node, do giemsa stains and diagnose under a microscope.

However, this rapid-diagnostic test has greatly improved access to care and massively reduced mortality.

Question 8

What treatment for visceral leishmaniasis in South-Asia?

Answer 8

ambisome. A single infusion is sufficient to treat a patient. Very effective and safe. Because there is only a single infusion needed, hospital stay and thus costs are reduced to a minimum. However, the price of the drug itself is high and it requires cold-chain.

Question 9

How does visceral leishmaniasis treatment differ in East Africa from treatment in South-Asia?

Answer 9

In East-Africa, ambisome is less effective. There, they rely on combination treatment with antimonials and paromomycin in intramuscular injections for 17 days. It is effective, but has significant toxicity. It is more costly, as the patients need to be in the hospital for those 17 days. In addition, there are patients like HIV patients and pregnant women, who are contra-indicated for this treatment. They are treated with very high doses of ambisome.

Question 10

What is needed for good vector control?

Answer 10

Vector control requires knowledge about the local epidemiology: what are the vector habitats, what is the interaction between the vector and humans. You can target these factors in the interventions.

Question 11

Is insecticide spraying useful in vector control?

Answer 11

In East-Africa the main vector is Phlebotomus orientalis, which is a sylvatic vector that lives in the acacia forests. These forests are big (in South-Sudan an area the size of France), so insecticide spraying is not an option. In South-Asia the vector is Phlebotomus argentipus, which is a domestic fly that lives in and around the houses. Insecticide spraying is thus an option!

Question 12

Are bed nets useful in vector control?

Answer 12

There is conflicting evidence on bed nets. More research is needed. Effectiveness is dependent on behaviour, as sand flies are not perceived as a threat and bed nets are thus not used

Question 13

What did the response during recent epidemics show?

Answer 13

Epidemic response showed that early diagnostic and treatment is the most important in outbreak settings

Question 14

Is there a vaccine for visceral leishmaniasis?

Answer 14

Currently there is no vaccine, although research is being done. It is unlikely that there will be a vaccine in the next 5 years.

Question 15

Is it worth it to intervene in cutaneous leishmaniasis?

Answer 15

Yes. It has a very high burden of disease (~1 million new cases/year). Untreated cutaneous leishmaniasis can lead to disfiguring lesions and scarring. It is also a very stigmatizing disease. It can also progress to mucosal leishmaniasis, which is very painful.

Question 16

Where are the most cases of cutaneous leishmaniasis?

Answer 16

Most cases are in the Middle East, Asia and Brazil. The vector is the sand fly, there is a zoonotic version where the animal is the reservoir and a non-zoonotic version where the human is the reservoir. Quite often a gerbil as an animal reservoir. Over the last years, there is an increase in the number of cases. This increase is only caused by an increase in cases in the eastern Mediterranean region (Middle East and Northern Africa). This is mainly caused in countries where there is conflict, meaning that there is a relationship between the occurrence of leishmaniasis and conflict.

Question 17

Why is there more cutaneous leishmaniasis in countries in conflict?

Answer 17

The relationship between the occurrence of cutaneous leishmaniasis and conflict can be explained by deterioration of healthcare and high levels of population displacement in areas of conflict.

Question 18

What are the clinical symptoms of cutaneous leishmaniasis?

Answer 18

Cutaneous leishmaniasis starts as a raised papule on the site of the bite, then it grows into a nodule or plaque over several years. A crust covering an ulcer usually develops, after which a raised edge with a variable surrounding develops. In the old world (Asia, Africa, Europe), the main agents are leishmania major and leishmania tropica. Leishmania major causes the wet ulcers, leishmania tropica causes the dry ulcers. Persistent leishmania tropica can even lead to severe deformities.

Question 19

How is cutaneous leishmaniasis treated?

Answer 19

With antimonials (topical or systemic), cryotherapy, thermotherapy. This drug is very toxic, but it is the only one with evidence of effectivity. It requires 8-12 injections in the lesion. There is a trial starting with a combination of oral drugs and thermotherapy.

Question 20

What is done in terms of disease control for cutaneous leishmaniasis?

Answer 20

The same as for visceral leishmaniasis. Vector control (removing sand flies, spraying, long-lasting insecticide, environmental control) and reservoir control (removing animals or their homes, active case finding and early testing and treatment of humans)