Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria at sentinel sites in Mozambique, 2015

he resistance of Plasmodium falciparum to anti-malarial drugs continues to challenge malaria control. We assessed the therapeutic efficacy and safety of artemether-lumefantrine (AL), the first-line treatment of uncomplicated P. falciparum malaria, in children under five years of age in Mozambique. We conducted a prospective one-arm study to evaluate the clinical and parasitological efficacy of AL over 28days at four sentinel sites, using the WHO protocol for assessing the efficacy of antimalarial treatment. msp1, msp2 and glurp genes were analysed by DNA polymerase chain reaction (PCR) to differentiate recrudescence from re-infection with malaria parasites. Haemoglobin concentration was recorded at baseline and on days 7, 14 and 28. A total of 349 children with uncomplicated falciparum malaria were recruited at the four sentinel sites. Adequate clinical and parasitological response to AL on day 28 follow-up varied from 96.3% to 100% after correction by PCR. The drug was well tolerated, and no adverse event related to the drug was reported. AL, the current first-line treatment for uncomplicated falciparum malaria in Mozambique, remains highly efficacious at the study sites. Monitoring of the efficacy of the recommended antimalarial drugs should be continued in order to detect any emerging threat to their efficacy.

Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria at sentinel sites in Mozambique, 2015.

The resistance of Plasmodium falciparum to anti-malarial drugs continues to challenge malaria control. We assessed the therapeutic efficacy and safety of artemether-lumefantrine (AL), the first-line treatment of uncomplicated P. falciparum malaria, in children under five years of age in Mozambique. We conducted a prospective one-arm study to evaluate the clinical and parasitological efficacy of AL over 28days at four sentinel sites, using the WHO protocol for assessing the efficacy of antimalarial treatment. msp1, msp2 and glurp genes were analysed by DNA polymerase chain reaction (PCR) to differentiate recrudescence from re-infection with malaria parasites. Haemoglobin concentration was recorded at baseline and on days 7, 14 and 28. A total of 349 children with uncomplicated falciparum malaria were recruited at the four sentinel sites. Adequate clinical and parasitological response to AL on day 28 follow-up varied from 96.3% to 100% after correction by PCR. The drug was well tolerated, and no adverse event related to the drug was reported. AL, the current first-line treatment for uncomplicated falciparum malaria in Mozambique, remains highly efficacious at the study sites. Monitoring of the efficacy of the recommended antimalarial drugs should be continued in order to detect any emerging threat to their efficacy. TRIAL REGISTRATION NUMBER: ACTRN12616001680459.

Preliminary report of HIV and Toxoplasma gondii occurrence in pregnant women from Mozambique / Descrição preliminar da ocorrência de infecção pelo HIV e toxoplasmose em mulheres grávidas em Moçambique

Toxoplasmosis, a protozoan disease, causes severe disease in fetuses during pregnancy and deadly encephalitis in HIV patients. There are several studies on its seroprevalence around the world, but studies focusing on African countries are limited in number and mostly anecdotal. We studied two groups of samples from Mozambique by ELISA, using serum samples from 150 pregnant women and six Cerebrospinal fluid (CSF) samples from AIDS patients with encephalitis. HIV status was confirmed, and CD4 blood counts were obtained from HIV-positive pregnant women. IgG seroprevalence of the group as a whole was 18.7 percent (28/150), with a higher prevalence in HIV-positive individuals compared to those who were HIV-negative (31.3 percent, [18/58] vs. 10.9 percent, [10/92]) patients. These data may be biased due to cumulative effects of exposition affecting disease prevalence. If corrected, this data may indicate an interaction of HIV and T. gondii. Prevalence of both diseases increases with age, but this is more clearly seen for toxoplasmosis (p < 0.005) than HIV infection, possibly explained by higher transmission of HIV after childhood. In HIV patients suffering from encephalitis, CSF serology showed that 33 percent of specific IgG CSF had a high avidity, which was in accordance with the data from the group of pregnant women. Lower prevalence rates of both infections in older groups could be explained by more deaths in the infected groups, resulting in an artificially lower prevalence. Using CD4 counts as a marker of time of HIV infection, and correcting for age, patients with contact with T. gondii had fewer CD4 cells, suggesting prolonged HIV disease or other causes. Toxoplasma IgG prevalence is higher in HIV+ groups, which could be ascribed to HIV- and T. gondii-associated risk factors, such as exposure to higher and more diverse social contacts. The low incidence of Toxoplasma IgG in younger age groups shows that transmission could be related to better access to cyst-containing meat in adulthood, as environmental transmission due to oocysts is usually blamed for higher incidence in children. Taken together, these data support the urgent need of research in toxoplasmosis in Africa, especially in the presence of HIV epidemics.

Toxoplasmose, uma protozoonose, causa doença grave em fetos de mulheres grávidas com infecção aguda e encefalite letal em portadores de HIV. Apesar de muitos estudos sobre sua prevalência no Mundo, existem apenas alguns relatos da toxoplasmose na África Austral, geralmente anedóticos. Estudamos por ELISA dois grupos de amostras de Moçambique, usando 150 amostras de soros de mulheres grávidas e seis amostras de Liquido Cefalorraquidiano (LCR) de pacientes com AIDS e encefalite. O estado da infecção pelo HIV foi confirmado e a contagem de células CD4+ no sangue foi obtida das pacientes grávidas infectadas pelo HIV. No grupo das gestantes, IgG anti T.gondii foi encontrada em 18.7 por cento (28/150), mais freqüente em pacientes HIV positivas (31.3 por cento, 18/58) do que em HIV negativas (10.9 por cento, 10/92). A ocorrência de ambas as doenças aumenta com a idade, mais claramente vista na toxoplasmose (p < 0.005) do que na infecção pelo HIV, devido maior transmissão do HIV após a infância. Na encefalite em pacientes HIV+, a sorologia do LCR mostrou uma ocorrência de 33 por cento de IgG especifica de alta avidez, que está de acordo com a ocorrência neste grupo etário, baseado nos dados de nossas gestantes. A menor ocorrência de ambas as infecções em grupos etários mais idosos pode ser explicada pela mortalidade cumulativa por qualquer causa nos grupos mais idosos, resultando em menor ocorrência relativa. Usando as contagens de células CD4+ como marcadores da progressão da infecção pelo HIV e corrigindo para grupos etários, as gestantes HIV+ com contato com T. gondii tem menores níveis de células CD4+ do que as gestantes HIV+ sem contato com T.gondii. A ocorrência maior da toxoplasmose em gestantes HIV+ pode ser atribuída a fatores de risco semelhantes, como exposição a maior contato social. A baixa ocorrência da toxoplasmose em grupos mais jovens pode se relacionar com menor acesso a carne contendo cistos, já que a transmissão ambiental por oocistos está associada à maior incidência em crianças. Todos estes dados reforçam a necessidade de pesquisa da toxoplasmose na África Austral, especialmente na presença da epidemia pelo HIV.

Preliminary report of HIV and Toxoplasma gondii occurrence in pregnant women from Mozambique.

Toxoplasmosis, a protozoan disease, causes severe disease in fetuses during pregnancy and deadly encephalitis in HIV patients. There are several studies on its seroprevalence around the world, but studies focusing on African countries are limited in number and mostly anecdotal. We studied two groups of samples from Mozambique by ELISA, using serum samples from 150 pregnant women and six Cerebrospinal fluid (CSF) samples from AIDS patients with encephalitis. HIV status was confirmed, and CD4 blood counts were obtained from HIV-positive pregnant women. IgG seroprevalence of the group as a whole was 18.7% (28/150), with a higher prevalence in HIV-positive individuals compared to those who were HIV-negative (31.3%, [18/58] vs. 10.9%, [10/92]) patients. These data may be biased due to cumulative effects of exposition affecting disease prevalence. If corrected, this data may indicate an interaction of HIV and T. gondii. Prevalence of both diseases increases with age, but this is more clearly seen for toxoplasmosis (p < 0.005) than HIV infection, possibly explained by higher transmission of HIV after childhood. In HIV patients suffering from encephalitis, CSF serology showed that 33% of specific IgG CSF had a high avidity, which was in accordance with the data from the group of pregnant women. Lower prevalence rates of both infections in older groups could be explained by more deaths in the infected groups, resulting in an artificially lower prevalence. Using CD4 counts as a marker of time of HIV infection, and correcting for age, patients with contact with T. gondii had fewer CD4 cells, suggesting prolonged HIV disease or other causes. Toxoplasma IgG prevalence is higher in HIV+ groups, which could be ascribed to HIV- and T. gondii-associated risk factors, such as exposure to higher and more diverse social contacts. The low incidence of Toxoplasma IgG in younger age groups shows that transmission could be related to better access to cyst-containing meat in adulthood, as environmental transmission due to oocysts is usually blamed for higher incidence in children. Taken together, these data support the urgent need of research in toxoplasmosis in Africa, especially in the presence of HIV epidemics.