Breakthrough Clinical Results
Novartis announced that Coartem® (artemether-lumefantrine) Baby, also known as Riamet® Baby, has received approval from Swissmedic as the first malaria medicine for newborns and young infants. This new treatment, developed in collaboration with Medicines for Malaria Venture (MMV), addresses a significant treatment gap for infants under 4.5 kg. The approval is based on the Phase II/III CALINA study, demonstrating efficacy and safety in this vulnerable population. Novartis plans to make the treatment widely available on a largely not-for-profit basis in malaria-endemic regions. Eight African countries are expected to rapidly approve the drug under a special global health scheme.
Key Highlights
- First malaria medicine approved for newborns and young infants (under 4.5 kg)
- Developed in collaboration with Medicines for Malaria Venture (MMV)
- Approval based on Phase II/III CALINA study
- Novartis plans for largely not-for-profit distribution in malaria-endemic areas
Incidence and Prevalence
Global Malaria Epidemiology: Current Evidence
Based on the available information, I cannot provide global estimates of malaria incidence and prevalence as this data is not present in the context. However, I can share regional data from specific studies that have been conducted in various countries.
Regional Prevalence Data
Asia
- In Quetta, Pakistan, a study of 1831 subjects found 18.45% (338) were positive for malarial parasites with species prevalence of 81.66% (276) for Plasmodium vivax and 18.34% (62) for Plasmodium falciparum
- In Mindanao, Philippines (2010-2013), malaria prevalence by PCR was 3.8% in Sarangani, 10% in South Cotabato, and 4.2% in Tawi-Tawi, with both P. falciparum and P. vivax identified in all three provinces, and one case of P. malariae in South Cotabato
- In Myanmar (2017), the overall malaria infection prevalence was 13.9% across four townships, with Paletwa having the highest rate (22.9%) and Thabeikkyin the lowest (3.9%)
- P. vivax was the most prevalent species in all locations in Myanmar, while P. falciparum accounted for 32% of infections in Paletwa township
- In Thailand's Tak province, 90.2% of Plasmodium infections were submicroscopic and asymptomatic, including many mixed-species infections
- Among febrile patients in Thailand, mixed-species infections comprised 68% of positive cases, all of which were misdiagnosed and undertreated
Africa
- In Gabon (2022), the overall prevalence of Plasmodium infection was 21.62% (211/976), with 19.35% in urban areas and 23.92% in rural areas
- In Dar es Salaam, Tanzania, school surveys showed low prevalence of malaria parasites: 0.8%, 1.4%, 2.7%, and 3.7% in the center, intermediate, periphery, and surrounding rural areas respectively
- In Dangassa, no Plasmodium infection was observed in HbAS children in the SMC arm, while in non-HbAS children, peaks of infection prevalence were observed in October (24.66%)
South America
- In La Italia (Chocó), Colombia, infection by Plasmodium was detected in 17% of cases with 62% due to P. falciparum and 27% due to P. vivax
Asymptomatic Infections
Asymptomatic infections were common in several studies: - 96.84% of infections in urban Gabon and 93.97% in rural Gabon were asymptomatic - In Thailand, a high proportion of infections were submicroscopic and asymptomatic
The data shows considerable regional variation in both prevalence rates and dominant Plasmodium species, with P. vivax being more common in many Asian settings while P. falciparum dominates in certain African and South American locations.
Risk Factors and Comorbidities
Risk Factors and Comorbidities for Malaria
Top Risk Factors for Malaria Occurrence
Lack of Proper Chemoprophylaxis
75% of U.S. civilians who acquired malaria during travel had not used a chemoprophylactic regimen recommended by CDC for the area in which they had traveled, making this a significant risk factor.
Blood Group Type
Blood group 'B' was significantly higher in patients with severe malaria compared to uncomplicated cases (P < 0.0001; OR = 4.09) and healthy controls (P < 0.0001; OR = 2.79). Carriers of blood group 'A' (P = 0.04) and 'AB' (P = 0.04) were also susceptible to malaria severity.
Age Factors
School-age children (5-15 years) had higher odds than adults of having gametocytes when infected (OR 2.77, 95% CI 1.47-5.19), representing an under-recognized reservoir of infection. Age is a significant risk factor for Plasmodium infections: - In Rourkela, India, asymptomatic infections were associated with young age (microscopy or RDT) - In Meghalaya, India, children (<16 years old) had significantly higher odds of being PCR positive than adults (≥16 years old) - In North Mara, Tanzania, prevalence rates for parasitemia were highest among the youngest age groups and lowest in those 35 years of age and older
Epidemiological Risk Factors
Housing Conditions
Living in unfinished houses was significantly associated with gametocyte presence. Infected people in unfinished houses had higher odds of carrying gametocytes (OR 2.24, 95% CI 1.16-4.31) and 31% (95% CI 3-65%) higher gametocyte density than those in finished houses.
Household Characteristics
In Meghalaya, India, risk of infection increased with presence of mosquitoes and electricity in households (OR = 1.19 and 1.11 respectively). Households with reported animals had reduced infection risk (OR = 0.91).
Gender
Gender plays a role in infection risk: - In Rourkela, India, asymptomatic infections were associated with male gender (microscopy or RDT) - Gender differences in complaints were noted in Rourkela only
Seasonal Variation
Seasonal variation affects infection rates: - In Rourkela, India, asymptomatic infections were associated with rainy season (PCR) - In Pakistan (Loralai area), highest P. falciparum infection (83.9%) was in September and lowest (65.3%) in January - In Pakistan (Musa Khel area), highest P. falciparum infection (76.9%) was in October and lowest in February
Geographic Location
Geographic location influences prevalence: - In India, P. vivax prevalence ranged from 2.4% in Punjab Province to 10.8% in Sindh Province - P. falciparum prevalence ranged from 0.1% in Islamabad to 3.8% in Balochistan - In PNG military bases, infection prevalence was significantly higher in Wewak (35.5%) and Vanimo (33.3%) than on Manus Island (11.8%)
Parasite Species-Specific Factors
In Rourkela, India, participants with P. vivax were more likely to be asymptomatic (61.1%) than persons with P. falciparum mono-infections (34.6%).
Comorbidities and Medical Conditions
Sickle Cell Disease (SCD)
Sickle cell disease (SCD) increases the risk of morbidity and mortality from malaria. In a case report, a 29-year-old woman with SCD presented with severe anemia beyond her typical baseline in the setting of P. falciparum malaria. The patient's underlying SCD contributed to the severity of the anemia and persistence of the malarial infection.
Malnutrition
Malnutrition can have a negative impact on malaria mortality and severity (41.2% of studies showed this association).
Autoimmune Hemolytic Anemia (AIHA)
Autoimmune hemolytic anemia (AIHA) in the setting of malarial infection can lead to severe hemolytic anemia with extensive packed red blood cell transfusion requirements.
Pregnancy
Pregnancy may be a risk factor, as evidenced by the case report of a pregnant woman with SCD who developed severe complications.
Congenital Adrenal Hyperplasia
Congenital adrenal hyperplasia was reported in a case of a 25-day-old premature female baby with mixed malarial infection who did not respond well to standard treatment.
Genetic Factors
Blood Group 'O' (Protective)
Studies consistently demonstrate that blood group 'O' confers resistance against severe falciparum infection. Prevalence of 'O' group in uncomplicated malaria (P < 0.0001; OR = 2.81) and healthy controls (P = 0.0003; OR = 2.16) was significantly high compared to severe malaria.
Sickle Cell Trait and Disease
Sickle cell trait (HbAS) and sickle cell disease (HbSS): The relative risk of malarial infection was 0.33 in HbSS compared to both HbAA and HbAS. The protection conferred by HbS against malaria is more marked in HbSS disease than in HbAS and is HbS-content related.
Genetic Mutations in Cytoskeletal Proteins
Many red blood cell disorders result from mutations in genes encoding cytoskeletal proteins and these are associated with increased protection against malarial infections, as demonstrated in studies with Ank-1 gene mutations.
Drug used in other indications
Coartem (Artemether-Lumefantrine) Clinical Indications Beyond Malaria
Based on a thorough review of the available information, there is no evidence of Coartem (artemether-lumefantrine) being trialed for any indications other than malaria. The existing data exclusively discusses artemether-lumefantrine in the context of malaria treatment, specifically for Plasmodium falciparum malaria and Plasmodium vivax malaria.
No information is available regarding: - Alternative clinical indications beyond malaria - Intervention models for non-malarial applications - Different dosing regimens for other conditions - Administration protocols for uses outside of malaria treatment
The current clinical focus of artemether-lumefantrine appears to remain solely on its established role as an antimalarial medication.