Treatment of neonates

It is today agreed that every case of congenital toxoplasmosis should be treated whether or not the newborn infant displays clinical manifestation. Treatment should be instituted as soon as possible after birth, and given for a minimum of 6 months, usually 1 year. Therapy beyond 12 months is only recommended in cases where the infection is still active. In infants with symptomatic congenital toxoplasmosis prospective studies from the United States using pyrimethamine-sulfadiazine continuously for a whole year showed striking effects on the ophthalmologic follow-up (Mets et al. 1996), neuro developmental outcome (McAuley et al. 1994), and hearing loss (McGee et al. 1992). The key question is whether or not treatment is necessary in sub-clinical cases with no symptoms at all. Controlled trials with long prospective follow-ups do not exist. There is, however, historical evidence that early treatment protects against development of late ocular lesions and cerebral symptoms (Wilson et al. 1980; Piene and Garin 1989). Pyrimethamine and sulfadiazine in combination have proven more effective than spiramycin alone.

The present guidelines recommend that symptomatic infants should be treated for at least 1 year with pyrimethamine-sulfadiazine. In cases with active chorioretinitis or cerebral infection, corticosteroides should be added.

Table 26.1 Treatment of Toxoplasma infection in pregnant women and newborn infants

Drugs

Adults

Newborn

Spiramycin

Pyrimethamine (P) Sulfadiazine (S)

25mg/day 50-100mg/kg/day (initially: double dose)

Fansidar

(1 tablet = 25 mg pyrimethamine + 500 mg sulfadoxine)

2 tablets/week

During pyrimethamine therapy:

Folinic acid (F) 15mg twice weekly

Blood cells counts (platelet, white cells) every 1-2 weeks

If ocular or CNS toxoplasmosis :

Corticosteroids

Indications

Pregnant women with acquired infection Before conception:

150000-300000IU/kg/day

0.5-1mg/kg/day 50-100mg/kg/day

1 tablet/20kg/week 3-5mg, twice weekly

1-2mg/kg/day

Suspected cases: Proven cases: 1st trimester: 2nd-3rd trimester:

Evidence of foetal infection:

Newborns with congenital infection Suspected infection: Subclinical congenital infection:

Overt congenital infection:

No need for treatment Spiramycin

Spiramycin continuously P + S + F (3 weeks) + Spiramycin (4-6 weeks) Alternative: Fansidar (2 tablets/week) P + S + F (3 weeks), then Spiramycin (3-6 weeks). Repeat until delivery

Spiramycin until diagnosis P + S + F (4 weeks) + Spiramycin (4-6 weeks) Repeat until 12 months of age Alternative: (a) P + S + F (3 months) (b) Fansidar 1 tablet/20kg/week P + S + F (from birth until 6-12 months), Alternative after 6 months of age: Spiramycin (4 weeks) + P + S + F (4 weeks)

In asymptomatic newborns the regimen varies. Traditionally, spiramycin is recommended during the first months of life, thereafter four-week courses of pyrimethamine-sulfadiazine alternating with six-week courses of spiramycin - altogether four courses during the first year of life (McLeod et al. 2000). In Denmark a single three-months course with pyrimethamine-sulfadiazine-folinic acid is recommended (Petersen and Eaton 2000). In France and Switzerland, Fansidar and folinic acid are given weekly during the first year.

Still, after 30 years of experience, the optimum schedules and duration of therapy during pregnancy and in newborns remain unknown. Future international multicentre studies with long-term follow-up observations are needed to provide sufficient data.

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