In October 2012, a cluster of illnesses and deaths was reported in Uganda and was confirmed to be an outbreak of Marburg virus disease (MVD). Patients meeting the case criteria were interviewed using a standard investigation form, and blood specimens were tested for evidence of acute or recent Marburg virus infection by reverse transcription–polymerase chain reaction (RT-PCR) and antibody enzyme-linked immunosorbent assay. The total count of confirmed and probable MVD cases was 26, of which 15 (58%) were fatal. Four of 15 laboratory-confirmed cases (27%) were fatal. Case patients were located in 4 different districts in Uganda, although all chains of transmission originated in Ibanda District, and the earliest case detected had an onset in July 2012. No zoonotic exposures were identified. Symptoms significantly associated with being a MVD case included hiccups, anorexia, fatigue, vomiting, sore throat, and difficulty swallowing. Contact with a case patient and attending a funeral were also significantly associated with being a case. Average RT-PCR cycle threshold values for fatal cases during the acute phase of illness were significantly lower than those for nonfatal cases. Following the institution of contact tracing, active case surveillance, care of patients with isolation precautions, community mobilization, and rapid diagnostic testing, the outbreak was successfully contained 14 days after its initial detection.

BackgroundIn October 2014, during the Ebola outbreak in Liberia healthcare services were limited while malaria transmission continued. Médecins Sans Frontières (MSF) implemented a mass drug administration (MDA) of malaria chemoprevention (CP) in Monrovia to reduce malaria-associated morbidity. In order to inform future interventions, we described the scale of the MDA, evaluated its acceptance and estimated the effectiveness.MethodsMSF carried out two rounds of MDA with artesunate/amodiaquine (ASAQ) targeting four neighbourhoods of Monrovia (October to December 2014). We systematically selected households in the distribution area and administered standardized questionnaires. We calculated incidence ratios (IR) of side effects using poisson regression and compared self-reported fever risk differences (RD) pre- and post-MDA using a z-test.FindingsIn total, 1,259,699 courses of ASAQ-CP were distributed. All households surveyed (n = 222; 1233 household members) attended the MDA in round 1 (r1) and 96% in round 2 (r2) (212/222 households; 1,154 household members). 52% (643/1233) initiated ASAQ-CP in r1 and 22% (256/1154) in r2. Of those not initiating ASAQ-CP, 29% (172/590) saved it for later in r1, 47% (423/898) in r2. Experiencing side effects in r1 was not associated with ASAQ-CP initiation in r2 (IR 1.0, 95%CI 0.49–2.1). The incidence of self-reported fever decreased from 4.2% (52/1229) in the month prior to r1 to 1.5% (18/1229) after r1 (p<0.001) and decrease was larger among household members completing ASAQ-CP (RD = 4.9%) compared to those not initiating ASAQ-CP (RD = 0.6%) in r1 (p<0.001).ConclusionsThe reduction in self-reported fever cases following the intervention suggests that MDAs may be effective in reducing cases of fever during Ebola outbreaks. Despite high coverage, initiation of ASAQ-CP was low. Combining MDAs with longer term interventions to prevent malaria and to improve access to healthcare may reduce both the incidence of malaria and the proportion of respondents saving their treatment for future malaria episodes.

Background: The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin derivatives have a short half-life, lumefantrine and amodiaquine may give rise to differing durations of post-treatment prophylaxis, an important additional benefit to patients in higher transmission areas. Methods: We analyzed individual patient data from 8 clinical trials of AL versus AS-AQ in 12 sites in Africa (n = 4214 individuals). The time to PCR-confirmed reinfection after treatment was used to estimate the duration of posttreatment protection, accounting for variation in transmission intensity between settings using hidden semi-Markov models. Accelerated failure-time models were used to identify potential effects of covariates on the time to reinfection. The estimated duration of chemoprophylaxis was then used in a mathematical model of malaria transmission to determine the potential public health impact of each drug when used for first-line treatment. Results: We estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7-15.7) for AL and 15.2 days (95% CI 12.8-18.4) for AS-AQ overall. However, the duration varied significantly between trial sites, from 8.7-18.6 days for AL and 10.2-18.7 days for AS-AQ. Significant predictors of time to reinfection in multivariable models were transmission intensity, age, drug, and parasite genotype. Where wild type pfmdr1 and pfcrt parasite genotypes predominated (<=20% 86Y and 76T mutants, respectively), AS-AQ provided~2-fold longer protection than AL. Conversely, at a higher prevalence of 86Y and 76T mutant parasites (> 80%), AL provided up to 1.5-fold longer protection than AS-AQ. Our simulations found that these differences in the duration of protection could alter

BackgroundSeasonal malaria chemoprevention (SMC) with sulphadoxine-pyrimethamine (SP) plus amodiaquine (AQ) is being scaled up in Sahelian countries of West Africa. However, the potential development of Plasmodium falciparum resistance to the respective component drugs is a major concern.MethodsTwo cross-sectional surveys were conducted before (August 2012) and after (June 2014) a pilot implementation of SMC in Koutiala, Mali. Children aged 3–59 months received 7 rounds of curative doses of SP plus AQ over two malaria seasons. Genotypes of P. falciparum Pfdhfr codons 51, 59 and 108; Pfdhps codons 437 and 540, Pfcrt codon 76 and Pfmdr1codon 86 were analyzed by PCR on DNA from samples collected before and after SMC, and in non-SMC patient population as controls (November 2014).ResultsIn the SMC population 191/662 (28.9%) and 85/670 (12.7%) of children were P. falciparum positive by microscopy and were included in the molecular analysis before (2012) and after SMC implementation (2014), respectively. In the non-SMC patient population 220/310 (71%) were successfully PCR analyzed. In the SMC children, the prevalence of all molecular markers of SP resistance increased significantly after SMC including the Pfdhfr-dhps quintuple mutant genotype, which was 1.6% before but 7.1% after SMC (p = 0.02). The prevalence of Pfmdr1-86Y significantly decreased from 26.7% to 15.3% (p = 0.04) while no significant change was seen for Pfcrt 76T. In 2014, prevalence of all molecular markers of SP resistance were significantly higher among SMC children compared to the non-SMC population patient (p < 0.01). No Pfdhfr-164 mutation was found neither at baseline nor post SMC.ConclusionSMC increased the prevalence of molecular markers of P. falciparum resistance to SP in the treated children. However, there was no significant increase of these markers of resistance in the general parasite population after 2 years and 7 rounds of SMC.

Background: Severe acute malnutrition (SAM) affects almost all organs and has been associated with reduced intestinal absorption of medicines. However, very limited information is available on the pharmacokinetic properties of antimalarial drugs in this vulnerable population. We assessed artemether-lumefantrine (AL) clinical efficacy in children with SAM compared to those without.