Advertisement

Topics

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

2014-07-23 21:11:02 | BioPortfolio

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

Description

Malaria is a major contributor of the disease burden in Sub-Saharan Africa: some 90% of global cases occur in Sub-Saharan Africa, with pregnant women and children < 5 representing the most vulnerable population. P.falciparum infection in pregnancy leads to parasite sequestration in the maternal placental vascular space, causing increased risks of abortion, stillbirth, prematurity, intrauterine growth retardation and maternal anaemia; it is also associated with increased risk of low birth weight (LBW) and perinatal, neonatal and infant mortality.In low transmission areas, malaria can be severe with a high risk of maternal and perinatal mortality (up to 60-70%). In highly endemic areas, malaria is still associated with maternal anaemia, LBW and stillbirth. For prevention and control of malaria in pregnancy, the WHO recommends Intermittent Preventive Treatment (IPT), insecticide treated nets (ITNs) and effective case management for malaria and anaemia.

HIV-1 infection in pregnancy increases the risks of malaria. In HIV+ pregnant women, in addition, the efficacy of IPT with sulphadoxine-pyrimethamine (SP) appears decreased.

In Zambia, the malaria incidence rate increased from 121.5/1000 in 1976 to 482.0/1000 in 2003. The high rates were predominantly evident among pregnant women and children

Several studies in Zambia and Uganda demonstrated that daily cotrimoxazole (CTX) prophylaxis is effective in reducing mortality and morbidity in HIV+ individuals and that antibiotic therapy during pregnancy might impact positively to the reduction of adverse pregnancy outcomes. CTX prophylaxis significantly improves birth outcomes in HIV+ women with CD4<200/µl. A recent study in Zambia 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 an extremely low risk of malaria infection; CTX may have had a different impact if malaria transmission was either holo or hyperendemic. Today, WHO recommends daily CTX in addition to ARVs, to prevent opportunistic infections in HIV+, regardless of the background prevalence of CTX microbial resistance.

Concurrent administration of SP and CTX has been associated with increased incidence of severe adverse reactions in HIV+ patients. Therefore, WHO has promoted CTX prophylaxis as an alternative to SP for the IPT in immuno-compromised (CD4 < 350/µl)pregnant women. Unfortunately, there is insufficient information on the effectiveness of daily CTX for preventing malaria infection (placental parasitaemia) and its consequences (maternal anaemia and low birth weight) in pregnancy: so, presently, SP is the only antimalarial treatment for which data on efficacy and safety for IPT is available, and the WHO recommends that at least 2 doses of SP are given after the first trimester. With the documented 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.

The focus of this study is the malaria related outcome in pregnancy: we will target both HIV negative and HIV positive pregnant women, assuming that CTX is not inferior to SP in reducing placental parasitaemia. Such information is urgently needed in order to issue updated, effective guidelines on intermittent preventive treatment in pregnant women.

An open label clinical trial is the best design to assess the research question and its consequences on the offspring, both in HIV negative pregnant women and in HIV positive pregnant women with CD4 count ≥350/µl. The parallel design was chosen evaluate to each group separately, as HIV might interact with CTX efficacy. Offsets for efficacy were based on literature review.

Study Design

Allocation: Randomized, Control: Active Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Conditions

Malaria in Pregnancy

Intervention

Cotrimoxazole prophylaxis, SP IPT

Location

Kabuta Health Centre
Kabuta
Nchelenge District, Luapula Province of
Zambia

Status

Not yet recruiting

Source

Institute of Tropical Medicine, Belgium

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-07-23T21:11:02-0400

Clinical Trials [1433 Associated Clinical Trials listed on BioPortfolio]

Daily Co-trimoxazole Prophylaxis to Prevent Malaria in Pregnancy

Malaria is a major contributor of disease burden in Sub-Saharan Africa, and pregnant women and children are the most vulnerable population. Malaria in pregnancy increases the risks of abor...

Cotrimoxazole Prophylaxis Cessation Study Among Stabilized HIV-Infected Adult Patients on HAART in Entebbe, Uganda

According to the national guidelines in Uganda and to the World Health Organization guidelines, HIV-infected patients should receive cotrimoxazole prophylaxis indefinitely. There are, howe...

Prevention of P. Vivax Malaria During Pregnancy in Bolivia

The purpose of this study is to determine which, between weekly prophylaxis or malaria attack treatment, both by chloroquine, is the most appropriate way to protect women and foetus from P...

Impact of Cotrimoxazole Prophylaxis for HIV-Infected Adults on Antifolate Resistance

At least three studies in sub-Saharan Africa have demonstrated a decrease in morbidity or mortality among HIV-infected adults who took daily cotrimoxazole (trimethoprim sulfamethoxazole) [...

Prophylaxis Again Malaria to Enhance Child developmenT (PROTECT Study)

Each year, ~85.3 million pregnant women are at risk of becoming infected with Plasmodium falciparum(1). Among women in sub-Saharan Africa, most of whom have some degree of clinical immunit...

PubMed Articles [3120 Associated PubMed Articles listed on BioPortfolio]

Additional Screening and Treatment of Malaria During Pregnancy Provides Further Protection Against Malaria and Nonmalarial Fevers During the First Year of Life.

Although consensus exists that malaria in pregnancy (MiP) increases the risk of malaria in infancy, and eventually nonmalarial fevers (NMFs), there is a lack of conclusive evidence of benefits of MiP ...

Placental but Not Peripheral Plasmodium falciparum Infection During Pregnancy Is Associated With Increased Risk of Malaria in Infancy.

Pregnancy-associated Plasmodium falciparum infection impacts the health of mothers and newborns, but little is known about the effects of these infections on infant susceptibility to malaria. We follo...

Effects of concurrent exposure to antiretrovirals and cotrimoxazole prophylaxis among HIV-exposed, uninfected infants.

Given the potential of Cotrimoxazole preventive therapy (CPT) to prevent bacterial and malarial infections in HIV exposed, uninfected (HEU) infants, it is important to evaluate the effects of its conc...

Systemic Inflammatory Response to Malaria During Pregnancy Is Associated With Pregnancy Loss and Preterm Delivery.

Pregnancy malaria (PM) is associated with a proinflammatory immune response characterized by increased levels of cytokines and chemokines such as tumor necrosis factor-α, interferon-γ, interleukin 1...

Updated CDC Recommendations for Using Artemether-Lumefantrine for the Treatment of Uncomplicated Malaria in Pregnant Women in the United States.

Malaria infection during pregnancy is associated with an increased risk for maternal and fetal complications. In the United States, treatment options for uncomplicated, chloroquine-resistant Plasmodiu...

Medical and Biotech [MESH] Definitions

A biguanide compound which has little antimalarial activity until metabolized in the body to the active antimalarial agent cycloguanil. The usefulness of proguanil is limited by the rapid development of drug resistance by the malarial parasite. The hydrochloride is used for the casual prophylaxis of falciparum malaria, to suppress other forms of malaria, and to reduce transmission of infection (From Martindale, The Extra Pharmacopoeia, 30th ed, p405)

Malaria caused by PLASMODIUM VIVAX. This form of malaria is less severe than MALARIA, FALCIPARUM, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day.

Vaccines made from antigens arising from any of the four strains of Plasmodium which cause malaria in humans, or from P. berghei which causes malaria in rodents.

A protozoan parasite that causes vivax malaria (MALARIA, VIVAX). This species is found almost everywhere malaria is endemic and is the only one that has a range extending into the temperate regions.

Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.

More From BioPortfolio on "Establishing Effectiveness of Daily Co-trimoxazole Prophylaxis For Prevention of Malaria in Pregnancy"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Infectious-diseases
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...

Obstetrics and gynaecology
Fertility Menopause Obstetrics & Gynaecology Osteoporosis Women's Health Obstetrics and gynaecology comprises the care of the pregnant woman, her unborn child and the management of diseases specific to women. Most consultant...

Women's Health
Women's Health - key topics include breast cancer, pregnancy, menopause, stroke Follow and track Women's Health News on BioPortfolio: Women's Health News RSS Women'...


Searches Linking to this Trial