Case 1: Immunosuppressed patient

Date: January 2022

Expert: We would like to extend a very special thank you to Leo G. Visser, MD,
PhD | Leiden University Medical Center | Department of Infectious Diseases
for his valuable time in providing the expert opinion.

Using references to the drug information and biochemistry data (A+B) what is your advice to
Richard regarding

A) Receiving yellow fever vaccination for high-risk area

The older age, the underlying immunosuppressive condition of multiple myeloma potentially
affecting the quality and quantity of the antibody response, the low CD4-count (< 200), and the
high dose of glucocorticosteroids (50 mg of prednison) increase the risk of severe YFV-
associated visceral or neurological disease

On the other hand, outbreaks of yellow fever have not been reported in Kenya until 1992 in the
Rift Valley Province. This outbreak was a classical example of sylvatic yellow fever, occurring in
the rural area of Keiyo (Kerio Valley), Baringo and Koibatek Districts, and associated with bush
clearing [https://doi.org/10.4269/ajtmh.1998.59.644]. The Masai Mara is situated south and
outside of this region.

Balancing the higher risk of severe adverse reactions and low risk of infection, I would therefore
advice against YF vaccination, and issue a letter to exempt from vaccination if required.
Stringent adherence to mosquito bite prevention and use of permethrin spraying of clothing
help to reduce bites of the local vector Aedes africanus
[https://doi.org/10.4269/ajtmh.1998.59.650].

B) Which is the best choice for malaria prophylaxis in high-risk area.

Although off-label, my first choice would be atovaquone/proguanil, based on destination and

duration of travel. The caveat here is the chronic kidney disease which may affect renal
clearance of proguanil and its metabolite cycloguanil. Individuals with a creatinine clearance
less than 20 ml/min are at risk for megaloblastic anemia because of interference with
tetrahydrofolate synthesis by accumulating drug levels of proguanil and its more active
metabolite cycloguanil [DOI 10.1007/s00228-010-0824-3]. The short duration of drug use (3
weeks) is unlikely to cause severe side effects, unless there is already a pre-existent folic acid
deficiency. I would prescribe folic acid, 5 mg once daily to counteract the inhibition of proguanil
and cycloguanil on the human enzyme dihydrofolate reductase. As the synergistic activity of
proguanil to atovaquone is independent of this enzyme activity, the addition of folic acid will
not interfere with the antimalarial activity of atovaquone/proguanil
[https://doi.org/10.1016/S0035-9203(03)90162-3]. Alternatively, mefloquine could be used.
Tafenoquine is not available in Europe, and the pharmacokinetics of tafenoquine have not been
studied in patients with renal impairment.
C) What are other health risks to be considered with this traveller.

Advanced multiple myeloma may lead to hypoglobulinaemia and increased risk of infections
with capsulated extracellulair pathogens, such as pneumococci and Haemophilus influenzae
type b.

The high dose of prednison and low CD4-count increases the risk of invasive infections with
intracellulair pathogens, such as non-typhoid Salmonellae (and tuberculosis).

The chronic kidney disease will reduce the capability to concentrate the urine by extracting free
water increasing the risk of dehydration, especially in case of diarrhea.

Additional health advice may include:

1. Vaccination with the 23-valent pneumococcal vaccine. The pre-travel window of 6 weeks is
too small for the 13-valent conjugate vaccine followed by the 23-valent vaccine. The
pneumococcal serotypes included in the 13-valent vaccine are tailored on the Western world,
explaining my preference for the 23-valent vaccine.

2. Vaccination with Vi capsular polysaccharide vaccine against typhoid fever.

3. Stand-by antibiotic treatment with quinolones in case of diarrhea with fever, and oral
rehydration solution in case of diarrhea.
Depending on the frequency of recurrent respiratory tract infections, amoxicillin or amoxicillin-
clavulanic acid may be described as stand-by treatment of febrile respiratory tract infections.