Intermittent Preventive Treatment (IPTi) for the Prevention of Malaria and Anaemia in PNG Infants

Condition(s) targeted: Malaria; Anemia

Intervention: Amodiaquine/sulphadoxine-pyrimethamine, Artesunate/sulphadoxine-pyrimethamine or placebo (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: Papua New Guinea Institute of Medical Research

Official(s) and/or principal investigator(s):
Ivo Mueller, PhD, Principal Investigator, Affiliation: Papua New Guinea Institute of Medical Research
John Reeder, Prof, Principal Investigator, Affiliation: Papua New Guinea Institute of Medical Research

Overall contact:
Nicolas SENN, MD, Phone: +675 852 29 09, Email: nicolas.senn@gmail.com

In malaria-endemic areas, young children have an especially high risk of malaria morbidity and mortality. Malaria is estimated to cause up to 2 million deaths and 500 million clinical episodes in Africa alone. The bulk of disease in Africa and severe disease and deaths globally is due to P. falciparum. However, P. vivax is also responsible for a substantial disease burden in endemic regions outside Africa, where P. vivax may account for more than half of all malaria cases. Efforts to reduce this unacceptably high disease burden are hampered by the limited availability of affordable interventions. Following the cessation of large-scale vector control in highly endemic areas, malaria control efforts have centred on early diagnosis and treatment of clinical cases and reducing exposure through the use of insecticide-treated nets (ITNs). While ITNs have been shown to significantly reduce the burden of malaria additional effective interventions are urgently needed.

Several trials have shown that chemoprophylaxis given to children at weekly or fortnightly intervals reduces morbidity from malaria in a number of different settings and populations.

An alternative approach has been to use intermittent preventive therapy (IPT) involving the administration of a full therapeutic dose of antimalarials at regular intervals. This is logistically easier to deliver, and is less costly, and may reduce problems of promoting drug resistance associated with regular chemoprophylaxis. Intermittent administration of sulphadoxine-pyrimethamine (SP) during antenatal clinic visits was shown to be highly effective in reducing malaria and anaemia in pregnant women and improving infant birth weights. IPT in pregnancy (IPTp) is now recommended by WHO for endemic regions of Africa.

Official title: Intermittent Preventive Treatment (IPTi) for the Prevention of Malaria and Anaemia in PNG Infants

Study design: Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Primary outcome:

Incidence of symptomatic malaria (due to any Plasmodium species) from 3 - 15 months of age

Incidence of symptomatic P. falciparum malaria from 3 - 15 months of age

Incidence of symptomatic P. vivax malaria from 3-15 months of age

Secondary outcome:

Incidence of moderate-to-severe (Hb < 8 g/dl) and severe anaemia (Hb<5 g/dl) from 3 - 15 months of age

Mean haemoglobin concentration and prevalence of moderate-to-severe anaemia (Hb < 8 g/dl) at 15 months of age

Prevalence and density of malaria parasitemia at 15 months of age

Prevalence of splenomegaly at 15 months of age

Incidence of symptomatic malaria from 15 - 27 months of age

9. Incidence of (symptomatic) moderate-to-severe (Hb < 8 g/dl) and severe anaemia (Hb<5 g/dl) from 15 - 27 months of age

10. Mean haemoglobin levels and prevalence of moderate-to-severe (Hb < 8 g/dl) or severe anaemia at 27 months of age

11. Prevalence and density of malaria parasitemia at 27 months of age

12. Prevalence of splenomegaly at 27 months of age.

Detailed description: Intermittent preventive treatment in infancy (IPTi) is one of the most promising recent interventions to reduce the devastating impact of malaria in early childhood. Although two African studies have provided the proof of principle, further studies are needed to address several key issues. IPTi needs additional evaluation in a variety of settings and populations, alternative drugs and treatment schedules need to be tested and the long-term effect of IPTi on risk of malaria illness through early childhood needs to be clarified.

Many of these issues are currently being addressed in a series of studies conducted under the auspice of the IPTi Consortium. However, all these studies are based in sub-Saharan Africa and are thus almost exclusively concerned with the potential of IPTi to prevent P. falciparum malaria.

In order to determine whether IPTi is also an effective intervention in areas where there is a high prevalence of non-falciparum infections, further studies outside Africa are urgently needed. In addition, although initial IPTi studies have not shown a rebound in malaria morbidity following the intervention, the influence of IPTi on the acquisition of functional malaria immunity needs further investigation.

This proposal brings together investigators, experience, and resources to conduct a clinical trial of IPTi complemented by careful epidemiologic and laboratory investigations in two highly endemic areas of Papua New Guinea, where infections with all 4 human Plasmodium species are common. The studies will be based at the PNG Institute for Medical Research, which has excellent infrastructure and a strong history of malaria research and community-based studies

Minimum age: 2 Months. Maximum age: 4 Months. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 3 months old living in the aera for the next 2 years, exlusive use of the study

health facilities

Exclusion Criteria:

- Known chronic illness, e. g. TB, diabetes, renal failure severe malnutrition

(weight-for-age (WAZ) < 60% percentile) severe anaemia (Hb < 5 g/dl), or permanent disability, that prevents or impedes study participation

Nicolas SENN, MD, Phone: +675 852 29 09, Email: nicolas.senn@gmail.com

Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea; Recruiting
Nicolas Senn, MD, Phone: +675 852 29 09, Email: nicolas.senn@gmail.com
John Reeder, Prof, Principal Investigator
Ivo Mueller, PhD, Principal Investigator
James Beeson, MBBS, MD, Sub-Investigator
Pascal Michon, PhD, Sub-Investigator
Stephen Rogerson, A/Prof, Sub-Investigator
Louis Schofield, PhD, Sub-Investigator
Peter Zimmerman, A/Prof, Sub-Investigator

Starting date: June 2006
Last updated: July 8, 2008