Establishing Effectiveness of Daily Co-trimoxazole Prophylaxis For Prevention of Malaria in Pregnancy

Summary

Malaria is a major contributor of disease burden in Sub-Saharan Africa: 90% of global cases occur there, and pregnant women and children under 5 years are the most vulnerable. Malaria in pregnancy increases risks of abortion, stillbirth, prematurity, intrauterine growth retardation and maternal anemia, and is associated with higher risk of low birth weight and perinatal, neonatal and infant mortality. For prevention and control of malaria in pregnancy, the WHO recommends Intermittent Preventive Treatment (IPT) with antimalarial drugs, insecticide treated nets (ITNs) and effective treatment of malaria and anemia.

HIV in pregnancy increases the risks of malaria, and it seems that the efficacy of IPT with the drug sulphadoxine-pyrimethamine (SP) is decreased in HIV+ pregnant women.

Malaria prevention in pregnancy in Zambia relies on ITNs and IPT with SP. Daily prophylaxis with cotrimoxazole (CTX) effectively reduces mortality and morbidity in HIV+ individuals, and antibiotic therapy during pregnancy might help to decrease adverse pregnancy outcomes. CTX prophylaxis improves birth outcomes in HIV+ women with CD4\<200/µl: a study concluded that antenatal provision of CTX was beneficial for HIV+ pregnant women with low CD4 but not in women with ≥200/µl (however, this study was carried out in an area with very low risk of malaria , and CTX may have a different effect depending on endemic conditions). The WHO recommends daily CTX in addition to ARVs, to prevent opportunistic infections in all HIV+ patients.

Concurrent administration of SP and CTX may increase the incidence of severe adverse reactions in HIV+ patients, so WHO has promoted CTX prophylaxis as an alternative to SP for the IPT in immuno-compromised pregnant women. Unfortunately, there is insufficient information on the effectiveness of daily CTX for preventing malaria infection in pregnancy: so, SP is still the only antimalarial recommended by WHO for this purpose. With the increase in SP resistance and with the newer antimalarials still being studied for safety and efficacy in pregnancy, CTX could be an alternative for SP in reducing malaria and malaria-related morbidity and mortality in pregnancy.

This study will try to to see if in HIV- and HIV+ pregnant women, CTX is not inferior to SP in reducing placental parasitaemia. Such information is needed to issue updated, effective guidelines on malaria prevention in pregnancy

Conditions

• Malaria in Pregnancy
• HIV Infections

Interventions

DRUG

Cotrimoxazole prophylaxis

Daily prophylaxis with cotrimoxazole

DRUG

SP IPT

Intermittent preventive treatment with sulphadoxine-pyrimethamine

Sponsors & Collaborators

• Tropical Diseases Research Centre, Zambia

  collaborator OTHER_GOV

• Institute of Tropical Medicine, Belgium

  lead OTHER

Principal Investigators

• Christine Manyando, MD · Tropical Diseases Research Centre, Zambia

• Umberto D'Alessandro, MD, PhD · Insitute of Tropical Medicine, Antwerp, Belgium

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

PARALLEL

Eligibility

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-09-30

Primary Completion

2012-12-31

Completion

2013-02-28

Countries

• Zambia