PLoS Negl Trop Dis. 2015 May 26;9(5):e0003796.

Single Versus Double Dose Praziquantel Comparison on Efficacy and Schistosoma mansoni Re-Infection in Preschool-Age Children in Uganda: A Randomized Controlled Trial.

Nalugwa A1, Nuwaha F2, Tukahebwa EM3, Olsen A4.
  • 1Child Health and Development Centre, Makerere University, Kampala, Uganda.
  • 2Disease Control and Prevention, Makerere University, Kampala, Uganda.
  • 3Vector Control Division, Ministry of Health, Kampala, Uganda.
  • 4Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.

 

Abstract

BACKGROUND: Schistosoma mansoni infection is proven to be a major health problem of preschool-age children in sub-Saharan Africa, yet this age category is not part of the schistosomiasis control program. The objective of this study was to compare the impact of single and double dose praziquantel (PZQ) treatment on cure rates (CRs), egg reduction rates (ERRs) and re-infection rates 8 months later, in children aged 1-5 years living along Lake Victoria, Uganda.

METHODOLOGY/PRINCIPAL FINDINGS: Infected children (n= 1017) were randomized to receive either a single or double dose of PZQ. Initially all children were treated with a single standard oral dose 40 mg/kg body weight of PZQ. Two weeks later a second dose was administered to children in the double dose treatment arm. Side effects were monitored at 30 minutes to 24 hours after each treatment. Efficacy in terms of CRs and ERRs for the two treatments was assessed and compared 1 month after the second treatment. Re-infection with S. mansoni was assessed in the same children 8 months following the second treatment. CRs were non-significantly higher in children treated with two 40 mg/kg PZQ doses (85.5%; 290/339) compared to a single dose (83.2%; 297/357). ERRs were significantly higher in the double dose with 99.3 (95%CI: 99.2-99.5) compared with 98.9 (95%CI: 98.7-99.1) using a single dose, (P = 0.01). Side effects occurred more frequently during the first round of drug administration and were mild and short-lived; these included vomiting, abdominal pain and bloody diarrhea. Overall re-infection rate 8 months post treatment was 44.5%.

CONCLUSIONS: PZQ is efficacious and relatively safe to use in preschool-age children but there is still an unmet need to improve its formulation to suit small children. Two PZQ doses lead to significant reduction in egg excretion compared to a single dose. Re-infection rates with S. mansoni 8 months post treatment is the same among children irrespective of the treatment regimen.

PMID: 26011733

 

Supplement

Schistosoma mansoni chemotherapy in preschool age children (1- 5 years) using praziquantel

Allen Nalugwa1*, Fred Nuwaha2, Edridah Muheki Tukahebwa3, Annette Olsen4

1 Child Health and Development Centre, Makerere University, Kampala, Uganda, 2 Disease Control and Prevention, Makerere University, Kampala, Uganda, 3 Vector Control Division, Ministry of Health, Kampala, Uganda, 4 Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark

 

Abstract

Schistosoma mansoni is one of the main blood fluke species that parasitizes human beings. The parasitic schistosome is spread by freshwater snails of genus Biomphalaria and humans get infected through contact with infested waters. Mass drug administration (MDA) with praziquantel for schistosomiasis is the main approach adopted by the Uganda national schistosomiasis control program to reduce related morbidity only in school age children and adults. Many recent studies, however, have revealed that children less than 6 years of age are also at higher risk of S. mansoni infection. The objective of this study was to investigate the effect of praziquantel treatment on S. mansoni infected preschool age children living along Lake Victoria, Uganda. Stool samples provided by preschool children aged 1-5 years were screened for S. mansoni eggs using the Kato-Katz technique. To minimize stomach upsets as well as reducing the bitter taste of PZQ, children were given a piece of bread, and orange juice was provided before and after drug administration. Abdominal discomfort and diarrhoea were observed and reported within 30 minutes to 24 hours after drug administration but these were mild and short-lived; they subsided in less than three hours. At 1 month post-treatment follow-up, 84.3% of the treated children were found free of S. mansoni eggs in their stool samples and therefore considered cured. Overall S. mansoni egg reduction rate was 99.1%. Children in the age group 12–24 months were all found egg negative (100%) in comparison to older children, aged 49–60 months, (77.9%, P<0.001). Cure rate tended to increase with decrease in S. mansoni infection intensity; it was lower among children with moderate (71.9%) and heavy (58.9 %) intensity of infections at baseline compared to those with light-intensity (96.6%) infection. Results of this study show that a standard oral dose of PZQ is safe and efficacious against S. mansoni infections among preschool-age children. We recommend that, preschool age children 1-5 years infected with schistosomiasis, be considered for treatment with praziquantel.

 

Additional text

The disease, intestinal schistosomiasis caused by S. mansoni, is of considerable public health relevance in the tropics and subtropics; about 200 million people are infected worldwide with 85% of the disease burden found in Sub-Saharan Africa. Approximately 20 million people are at risk of being infected in Uganda and 4 million individuals are estimated to be infected. In this study slides of 41.7mg Kato-Katz thick smears were prepared from stool specimens (Fig. 1) provided by preschool children and examined under a microscope (Fig. 2) to determine S. mansoni egg counts of the infected children.

fig1

Young children living on Lake Victoria shores actively get infected with schistosome parasites usually through bathing, playing or swimming in schistosome-infested waters. These children may also get exposed passively to infective water when bathed with lake water, which are carried back home.

Intestinal schistosomiasis is treated on a large scale using praziquantel, a large white bitter tablet containing 600mg of active ingredient. PZQ is the drug of choice because it is effective on all schistosome species, cheap, safe and has minimal side effects. The standard recommended dose is a single oral treatment of 40 mg/kg body weight sufficient to achieve cure rates of 60–90%. Upon oral intake, PZQ penetrates the tegument and rapidly moves through the tissues of schistosomes causing muscle contraction and damage; it attacks only the mature schistosome worms. Preschool-age children are not targeted in schistosomiasis preventive chemotherapy campaigns due to the limited documentation on the safety of PZQ in this age group.

fig2

Following parasitological screening, egg positive children were weighed and offered a standard oral dose of PZQ (40 mg/kg body weight). The tablets were crushed and mixed with drinking water to facilitate oral uptake in small children. For ethical reasons and proper drug administration, parents of the preschool children that were to be treated for schistosomiasis were requested to stay around. To minimize stomach upsets and mask the bitter taste of PZQ, children were given a piece of bread, and orange juice before and after drug administration (Fig. 3).

After giving the snack, the children in the presence of their parents or caregivers were given praziquantel drug according to their weight measurements by a qualified nurse. Parents or caregivers of the participating children were asked to report any symptoms/adverse events that occurred following treatment of their children to the field nurse or to the nearest dispensary within 24 hours of praziquantel treatment.

fig3 

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