Asymptomatic and symptomatic malaria during pregnancy has consequences for both mother and her of... more Asymptomatic and symptomatic malaria during pregnancy has consequences for both mother and her offspring. Unfortunately, there is insufficient information on the safety and efficacy of most antimalarials in pregnancy. Indeed, clinical trials assessing antimalarial treatments systematically exclude pregnancy for fear of teratogenicity and embryotoxicity. The little available information originates from South East Asia while in sub-Saharan Africa such information is still limited and needs to be provided. A Phase 3, non-inferiority, multicentre, randomized, open-label clinical trial on safety and efficacy of 4 ACT when administered during pregnancy was carried out in 4 African countries: Burkina Faso, Ghana, Malawi and Zambia. This is a four arm trial using a balanced incomplete block design. Pregnant women diagnosed with malaria are randomised to receive either amodiaquine-artesunate (AQ-AS), dihydroartemisinin-piperaquine (DHA-PQ), artemether-lumefantrine (AL), or mefloquine-artesun...
To compare the efficacy of atovaquone-proguanil (AP) and sulphadoxine-pyrimethamine (SP) in the t... more To compare the efficacy of atovaquone-proguanil (AP) and sulphadoxine-pyrimethamine (SP) in the treatment of malarial anaemia in Zambian children. An individually randomised, double-blind, controlled trial was undertaken in Zambian children with moderately severe anaemia and Plasmodium falciparum parasitaemia. The main trial endpoint was treatment failure defined as a need for blood transfusion or treatment with quinine, persistent anaemia or death within 14 days from the start of treatment. Secondary endpoints were parasitological and haematological findings 14 or 28 days after the start of treatment. A total of 128 children with a packed cell volume of <21% and >9% and P. falciparum parasitaemia received treatment with AP and 127 treatment with SP. Treatment failure occurred in 28 children (22%) who received SP and in 10 (8%) who received AP (OR: 3.34, 95% CI: 1.54, 7.21). Ten children required blood transfusion, all of whom were in the SP treatment group. Six children died, five of whom were in the AP group; none of the deaths were considered to be related directly to treatment. Atovaquone-proguanil proved more effective than SP in the treatment of malarial anaemia in an area with a modest level of SP resistance. AP is no longer available through the Malarone Donation Programme and is too expensive for routine use in Africa. However, this study has shown that in an area with a modest level of resistance to SP, use of a more effective antimalaria reduces the need for blood transfusion in children with malarial anaemia.
The American journal of tropical medicine and hygiene, 1999
Malaria poses a major health risk to people who are exposed to infection in malaria-endemic areas... more Malaria poses a major health risk to people who are exposed to infection in malaria-endemic areas. A randomized, double-blind, placebo-controlled study was conducted to determine the efficacy and safety of Malarone (250 mg of atovaquone/100 mg of proguanil hydrochloride per tablet) for the chemoprophylaxis of Plasmodium falciparum malaria in Zambia. Adult volunteers received a three-day treatment course of Malarone to eliminate pre-existing parasitemia and were then immediately randomized to treatment with either one Malarone tablet daily (n = 136), or one placebo tablet daily (n = 138) for at least 10 weeks. Malaria blood smears were prepared on a weekly basis and a failure of chemoprophylaxis was defined as any subject who had a positive blood smear, or who withdrew from the study due to a treatment-related adverse event. The prophylaxis success rates in the Malarone and placebo groups were 98% and 63%, respectively (P < 0.001). The most commonly reported adverse events with at...
The impact of HIV-1 infection on malaria is probably driven by the incapacity of the suppressed i... more The impact of HIV-1 infection on malaria is probably driven by the incapacity of the suppressed immune system to control the parasite load, resulting in a higher parasite load, incidence of clinical malaria and treatment failure in immune- suppressed HIV patients. Reports on the risk of hyperparasitaemia or severe malaria in HIV- infected individuals are limited. In Luanshya, where malaria is meso-endemic, adults with suspected severe malaria were screened and possibly recruited between December 2005 and March 2007. For each confirmed severe malaria case 2 matched controls, an adult with uncomplicated malaria and a ‘community’ control with no evident sign/symptom of diseases, were selected within a pre-defined time period. Matching criteria were gender, age and area of residence. HIV-1 infection and the related immune suppression were explored as risk factors. HIV-1 prevalence was 93.1% (27/29) among severe malaria cases, 51.7% (15/29) among uncomplicated malaria cases and 44.8% (13...
The burden of malaria has decreased dramatically within the past several years in parts of sub-Sa... more The burden of malaria has decreased dramatically within the past several years in parts of sub-Saharan Africa, including regions of Southern Africa. Important to effective regional malaria control in Southern Africa is the appreciation that the reductions in malaria have not been achieved uniformly, with some countries experiencing resurgence. Understanding the reasons for sustained low-level malaria transmission in the face
MMWR. Morbidity and mortality weekly report, Jan 28, 2014
Although scale-up of antiretroviral therapy (ART) since 2005 has contributed to declines of about... more Although scale-up of antiretroviral therapy (ART) since 2005 has contributed to declines of about 30% in the global annual number of human immunodeficiency (HIV)-related deaths and declines in global HIV incidence, estimated annual HIV-related deaths among adolescents have increased by about 50% and estimated adolescent HIV incidence has been relatively stable. In 2012, an estimated 2,500 (40%) of all 6,300 daily new HIV infections occurred among persons aged 15-24 years. Difficulty enrolling adolescents and young adults in ART and high rates of loss to follow-up (LTFU) after ART initiation might be contributing to mortality and HIV incidence in this age group, but data are limited. To evaluate age-related ART retention challenges, data from retrospective cohort studies conducted in seven African countries among 16,421 patients, aged ≥15 years at enrollment, who initiated ART during 2004-2012 were analyzed. ART enrollment and outcome data were compared among three groups defined by ...
The American journal of tropical medicine and hygiene, 2006
Whether administration of folic acid to children with malaria anemia is helpful is controversial.... more Whether administration of folic acid to children with malaria anemia is helpful is controversial. Therefore, we conducted a randomised, placebo-controlled trial of 14 days of treatment with folic acid (1 mg/d) in Zambian children with malaria anemia treated with either sulfadoxine/pyrimethamine (SP) or atovaquone/proguanil (AP). Among children who received SP, the prevalence of parasitemia was higher in children treated with folic acid than among those given placebo at days 3, 7, and 14 after the start of treatment, and the difference at day 3 was statistically significant (P = 0.013). Folic acid treatment had no effect on parasitemia in children treated with AP. Administration of folic acid led to a small increase in packed cell volume over that seen in the placebo group at days 14 and 28 after the start of treatment.
Tropical medicine & international health : TM & IH, 2006
To compare the efficacy of atovaquone-proguanil (AP) and sulphadoxine-pyrimethamine (SP) in the t... more To compare the efficacy of atovaquone-proguanil (AP) and sulphadoxine-pyrimethamine (SP) in the treatment of malarial anaemia in Zambian children. An individually randomised, double-blind, controlled trial was undertaken in Zambian children with moderately severe anaemia and Plasmodium falciparum parasitaemia. The main trial endpoint was treatment failure defined as a need for blood transfusion or treatment with quinine, persistent anaemia or death within 14 days from the start of treatment. Secondary endpoints were parasitological and haematological findings 14 or 28 days after the start of treatment. A total of 128 children with a packed cell volume of <21% and >9% and P. falciparum parasitaemia received treatment with AP and 127 treatment with SP. Treatment failure occurred in 28 children (22%) who received SP and in 10 (8%) who received AP (OR: 3.34, 95% CI: 1.54, 7.21). Ten children required blood transfusion, all of whom were in the SP treatment group. Six children died,...
Antibiotic therapy during pregnancy may be beneficial and impacts positively on the reduction of ... more Antibiotic therapy during pregnancy may be beneficial and impacts positively on the reduction of adverse pregnancy outcomes. No studies have been done so far on the effects of daily Co-trimoxazole (CTX) prophylaxis on birth outcomes. A phase 3b randomized trial was conducted to establish that daily CTX in pregnancy is not inferior to SP intermittent preventive treatment (IPT) in reducing placental malaria; preventing peripheral parasitaemia; preventing perinatal mortality and also improving birth weight. To establish its safety on the offspring by measuring the gestational age and birth weight at delivery, and compare the safety and efficacy profile of CTX to that of SP. Pregnant women (HIV infected and uninfected) attending antenatal clinic were randomized to receive either daily CTX or sulfadoxine-pyrimethamine as per routine IPT. Safety was assessed using standard and pregnancy specific measurements. Women were followed up monthly until delivery and then with their offspring up to six weeks after delivery. Data from 346 pregnant women (CTX = 190; SP = 156) and 311 newborns (CTX = 166 and SP = 145) showed that preterm deliveries (CTX 3.6%; SP 3.0%); still births (CTX 3.0%; SP 2.1%), neonatal deaths (CTX 0%; SP 1.4%), and spontaneous abortions (CTX 0.6%; SP 0%) were similar between study arms. The low birth weight rates were 9% for CTX and 13% for SP. There were no birth defects reported. Both drug exposure groups had full term deliveries with similar birth weights (mean of 3.1 Kg). The incidence and severity of AEs in the two groups were comparable. Exposure to daily CTX in pregnancy may not be associated with particular safety risks in terms of birth outcomes such as preterm deliveries, still births, neonatal deaths and spontaneous abortions compared to SP. However, more data are required on CTX use in pregnant women both among HIV infected and un-infected individuals. Clinicaltrials.gov NCT00711906.
Asymptomatic and symptomatic malaria during pregnancy has consequences for both mother and her of... more Asymptomatic and symptomatic malaria during pregnancy has consequences for both mother and her offspring. Unfortunately, there is insufficient information on the safety and efficacy of most antimalarials in pregnancy. Indeed, clinical trials assessing antimalarial treatments systematically exclude pregnancy for fear of teratogenicity and embryotoxicity. The little available information originates from South East Asia while in sub-Saharan Africa such information is still limited and needs to be provided. A Phase 3, non-inferiority, multicentre, randomized, open-label clinical trial on safety and efficacy of 4 ACT when administered during pregnancy was carried out in 4 African countries: Burkina Faso, Ghana, Malawi and Zambia. This is a four arm trial using a balanced incomplete block design. Pregnant women diagnosed with malaria are randomised to receive either amodiaquine-artesunate (AQ-AS), dihydroartemisinin-piperaquine (DHA-PQ), artemether-lumefantrine (AL), or mefloquine-artesun...
To compare the efficacy of atovaquone-proguanil (AP) and sulphadoxine-pyrimethamine (SP) in the t... more To compare the efficacy of atovaquone-proguanil (AP) and sulphadoxine-pyrimethamine (SP) in the treatment of malarial anaemia in Zambian children. An individually randomised, double-blind, controlled trial was undertaken in Zambian children with moderately severe anaemia and Plasmodium falciparum parasitaemia. The main trial endpoint was treatment failure defined as a need for blood transfusion or treatment with quinine, persistent anaemia or death within 14 days from the start of treatment. Secondary endpoints were parasitological and haematological findings 14 or 28 days after the start of treatment. A total of 128 children with a packed cell volume of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;21% and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;9% and P. falciparum parasitaemia received treatment with AP and 127 treatment with SP. Treatment failure occurred in 28 children (22%) who received SP and in 10 (8%) who received AP (OR: 3.34, 95% CI: 1.54, 7.21). Ten children required blood transfusion, all of whom were in the SP treatment group. Six children died, five of whom were in the AP group; none of the deaths were considered to be related directly to treatment. Atovaquone-proguanil proved more effective than SP in the treatment of malarial anaemia in an area with a modest level of SP resistance. AP is no longer available through the Malarone Donation Programme and is too expensive for routine use in Africa. However, this study has shown that in an area with a modest level of resistance to SP, use of a more effective antimalaria reduces the need for blood transfusion in children with malarial anaemia.
The American journal of tropical medicine and hygiene, 1999
Malaria poses a major health risk to people who are exposed to infection in malaria-endemic areas... more Malaria poses a major health risk to people who are exposed to infection in malaria-endemic areas. A randomized, double-blind, placebo-controlled study was conducted to determine the efficacy and safety of Malarone (250 mg of atovaquone/100 mg of proguanil hydrochloride per tablet) for the chemoprophylaxis of Plasmodium falciparum malaria in Zambia. Adult volunteers received a three-day treatment course of Malarone to eliminate pre-existing parasitemia and were then immediately randomized to treatment with either one Malarone tablet daily (n = 136), or one placebo tablet daily (n = 138) for at least 10 weeks. Malaria blood smears were prepared on a weekly basis and a failure of chemoprophylaxis was defined as any subject who had a positive blood smear, or who withdrew from the study due to a treatment-related adverse event. The prophylaxis success rates in the Malarone and placebo groups were 98% and 63%, respectively (P < 0.001). The most commonly reported adverse events with at...
The impact of HIV-1 infection on malaria is probably driven by the incapacity of the suppressed i... more The impact of HIV-1 infection on malaria is probably driven by the incapacity of the suppressed immune system to control the parasite load, resulting in a higher parasite load, incidence of clinical malaria and treatment failure in immune- suppressed HIV patients. Reports on the risk of hyperparasitaemia or severe malaria in HIV- infected individuals are limited. In Luanshya, where malaria is meso-endemic, adults with suspected severe malaria were screened and possibly recruited between December 2005 and March 2007. For each confirmed severe malaria case 2 matched controls, an adult with uncomplicated malaria and a ‘community’ control with no evident sign/symptom of diseases, were selected within a pre-defined time period. Matching criteria were gender, age and area of residence. HIV-1 infection and the related immune suppression were explored as risk factors. HIV-1 prevalence was 93.1% (27/29) among severe malaria cases, 51.7% (15/29) among uncomplicated malaria cases and 44.8% (13...
The burden of malaria has decreased dramatically within the past several years in parts of sub-Sa... more The burden of malaria has decreased dramatically within the past several years in parts of sub-Saharan Africa, including regions of Southern Africa. Important to effective regional malaria control in Southern Africa is the appreciation that the reductions in malaria have not been achieved uniformly, with some countries experiencing resurgence. Understanding the reasons for sustained low-level malaria transmission in the face
MMWR. Morbidity and mortality weekly report, Jan 28, 2014
Although scale-up of antiretroviral therapy (ART) since 2005 has contributed to declines of about... more Although scale-up of antiretroviral therapy (ART) since 2005 has contributed to declines of about 30% in the global annual number of human immunodeficiency (HIV)-related deaths and declines in global HIV incidence, estimated annual HIV-related deaths among adolescents have increased by about 50% and estimated adolescent HIV incidence has been relatively stable. In 2012, an estimated 2,500 (40%) of all 6,300 daily new HIV infections occurred among persons aged 15-24 years. Difficulty enrolling adolescents and young adults in ART and high rates of loss to follow-up (LTFU) after ART initiation might be contributing to mortality and HIV incidence in this age group, but data are limited. To evaluate age-related ART retention challenges, data from retrospective cohort studies conducted in seven African countries among 16,421 patients, aged ≥15 years at enrollment, who initiated ART during 2004-2012 were analyzed. ART enrollment and outcome data were compared among three groups defined by ...
The American journal of tropical medicine and hygiene, 2006
Whether administration of folic acid to children with malaria anemia is helpful is controversial.... more Whether administration of folic acid to children with malaria anemia is helpful is controversial. Therefore, we conducted a randomised, placebo-controlled trial of 14 days of treatment with folic acid (1 mg/d) in Zambian children with malaria anemia treated with either sulfadoxine/pyrimethamine (SP) or atovaquone/proguanil (AP). Among children who received SP, the prevalence of parasitemia was higher in children treated with folic acid than among those given placebo at days 3, 7, and 14 after the start of treatment, and the difference at day 3 was statistically significant (P = 0.013). Folic acid treatment had no effect on parasitemia in children treated with AP. Administration of folic acid led to a small increase in packed cell volume over that seen in the placebo group at days 14 and 28 after the start of treatment.
Tropical medicine & international health : TM & IH, 2006
To compare the efficacy of atovaquone-proguanil (AP) and sulphadoxine-pyrimethamine (SP) in the t... more To compare the efficacy of atovaquone-proguanil (AP) and sulphadoxine-pyrimethamine (SP) in the treatment of malarial anaemia in Zambian children. An individually randomised, double-blind, controlled trial was undertaken in Zambian children with moderately severe anaemia and Plasmodium falciparum parasitaemia. The main trial endpoint was treatment failure defined as a need for blood transfusion or treatment with quinine, persistent anaemia or death within 14 days from the start of treatment. Secondary endpoints were parasitological and haematological findings 14 or 28 days after the start of treatment. A total of 128 children with a packed cell volume of <21% and >9% and P. falciparum parasitaemia received treatment with AP and 127 treatment with SP. Treatment failure occurred in 28 children (22%) who received SP and in 10 (8%) who received AP (OR: 3.34, 95% CI: 1.54, 7.21). Ten children required blood transfusion, all of whom were in the SP treatment group. Six children died,...
Antibiotic therapy during pregnancy may be beneficial and impacts positively on the reduction of ... more Antibiotic therapy during pregnancy may be beneficial and impacts positively on the reduction of adverse pregnancy outcomes. No studies have been done so far on the effects of daily Co-trimoxazole (CTX) prophylaxis on birth outcomes. A phase 3b randomized trial was conducted to establish that daily CTX in pregnancy is not inferior to SP intermittent preventive treatment (IPT) in reducing placental malaria; preventing peripheral parasitaemia; preventing perinatal mortality and also improving birth weight. To establish its safety on the offspring by measuring the gestational age and birth weight at delivery, and compare the safety and efficacy profile of CTX to that of SP. Pregnant women (HIV infected and uninfected) attending antenatal clinic were randomized to receive either daily CTX or sulfadoxine-pyrimethamine as per routine IPT. Safety was assessed using standard and pregnancy specific measurements. Women were followed up monthly until delivery and then with their offspring up to six weeks after delivery. Data from 346 pregnant women (CTX = 190; SP = 156) and 311 newborns (CTX = 166 and SP = 145) showed that preterm deliveries (CTX 3.6%; SP 3.0%); still births (CTX 3.0%; SP 2.1%), neonatal deaths (CTX 0%; SP 1.4%), and spontaneous abortions (CTX 0.6%; SP 0%) were similar between study arms. The low birth weight rates were 9% for CTX and 13% for SP. There were no birth defects reported. Both drug exposure groups had full term deliveries with similar birth weights (mean of 3.1 Kg). The incidence and severity of AEs in the two groups were comparable. Exposure to daily CTX in pregnancy may not be associated with particular safety risks in terms of birth outcomes such as preterm deliveries, still births, neonatal deaths and spontaneous abortions compared to SP. However, more data are required on CTX use in pregnant women both among HIV infected and un-infected individuals. Clinicaltrials.gov NCT00711906.
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