Artemether-lumefantrine efficacy among adults on antiretroviral therapy in Malawi.

BACKGROUND: When people with human immunodeficiency virus (HIV) infection (PWH) develop malaria, they are at risk of poor anti-malarial treatment efficacy resulting from impairment in the immune response and/or drug-drug interactions that alter anti-malarial metabolism. The therapeutic efficacy of artemether-lumefantrine was evaluated in a cohort of PWH on antiretroviral therapy (ART) and included measurement of day 7 lumefantrine levels in a subset to evaluate for associations between lumefantrine exposure and treatment response. METHODS: Adults living with HIV (≥ 18 years), on ART for ≥ 6 months with undetectable HIV RNA viral load and CD4 count ≥ 250/mm3 were randomized to daily trimethoprim-sulfamethoxazole (TS), weekly chloroquine (CQ) or no prophylaxis. After diagnosis of uncomplicated Plasmodium falciparum malaria, a therapeutic efficacy monitoring was conducted with PCR-correction according to WHO guidelines. The plasma lumefantrine levels on day 7 in 100 episodes of uncomplicated malaria was measured. A frailty proportional hazards model with random effects models to account for clustering examined the relationship between participant characteristics and malaria treatment failure within 28 days. Pearson's Chi-squared test was used to compare lumefantrine concentrations among patients with treatment failure and adequate clinical and parasitological response (ACPR). RESULTS: 411 malaria episodes were observed among 186 participants over 5 years. The unadjusted ACPR rate was 81% (95% CI 77-86). However, after PCR correction to exclude new infections, ACPR rate was 94% (95% CI 92-97). Increasing age and living in Ndirande were associated with decreased hazard of treatment failure. In this population of adults with HIV on ART, 54% (51/94) had levels below a previously defined optimal day 7 lumefantrine level of 200 ng/ml. This occurred more commonly among participants who were receiving an efavirenz-based ART compared to other ART regimens (OR 5.09 [95% CI 1.52-7.9]). Participants who experienced treatment failure had lower day 7 median lumefantrine levels (91 ng/ml [95% CI 48-231]) than participants who experienced ACPR (190 ng/ml [95% CI 101-378], p-value < 0.008). CONCLUSION: Recurrent malaria infections are frequent in this population of PWH on ART. The PCR-adjusted efficacy of AL meets the WHO criteria for acceptable treatment efficacy. Nevertheless, lumefantrine levels tend to be low in this population, particularly in those on efavirenz-based regimens, with lower concentrations associated with more frequent malaria infections following treatment. These results highlight the importance of understanding drug-drug interactions when diseases commonly co-occur.

Plasmodium falciparum community prevalence and health-seeking behaviours in rural Sussundenga District, Mozambique.

BACKGROUND: Impacts of nationally directed malaria control interventions hinge on understanding malaria transmission and prevention at the community level. The decision to seek care or health-seeking behaviours provide valuable insight on knowledge of malaria, access to care, and efficacy of malaria case management. Thus far, few studies have focused on central Mozambique. The aim was to describe community level Plasmodium falciparum prevalence and health-seeking behaviours among residents of Sussundenga, Mozambique, a rural village in Manica Province with high malaria incidence reported at the Sussundenga-Sede health centre (RHC). METHODS: A cross-sectional community-based survey was conducted from December 2019 to February 2020. A random household sampling method was used, based on enumerated households from satellite imagery. All consenting participants completed a survey about malaria risk, prevention, and health-seeking behaviours, and received a P. falciparum malaria rapid diagnostic test (RDT). RESULTS: The study enrolled 358 individuals from 96 households. The P. falciparum prevalence was 31.6% (95% CI [26.6-36.5%]). Ninety-three percent of participants reported using the Sussundenga-Sede RHC for healthcare. Sixty-six percent of participants (N = 233) experienced at least one malaria symptom in the past month, with self-reported fever most frequently reported (19.3%). Of these, 176 (76.5%) sought care in a health facility and 174 (79%) received an RDT with 130 (63%) having a positive test. Of those with a positive RDT, 127 (97%) received artemether-lumefantrine. Following treatment, 123 (97%) participants' symptoms resolved within a median of 3 days (IQR: 3-5) ranging from 2 to 14 days. In this high transmission setting, a high proportion of participants recognized malaria related symptoms then received a proper diagnostic test and treatment in a health facility. CONCLUSIONS: Future interventions that leverage this health-seeking behaviour and strengthen health systems for community interventions will improve malaria control and inform the efficacy of potential interventions at this particular international border.

Long-lasting household damage from Cyclone Idai increases malaria risk in rural western Mozambique.

Cyclone Idai in 2019 was one of the worst tropical cyclones recorded in the Southern Hemisphere. The storm caused catastrophic damage and led to a humanitarian crisis in Mozambique. The affected population suffered a cholera epidemic on top of housing and infrastructure damage and loss of life. The housing and infrastructure damage sustained during Cyclone Idai still has not been addressed in all affected communities. This is of grave concern because storm damage results in poor housing conditions which are known to increase the risk of malaria. Mozambique has the 4th highest malaria prevalence in sub-Saharan Africa and is struggling to control malaria in most of the country. We conducted a community-based cross-sectional survey in Sussundenga Village, Manica Province, Mozambique in December 2019-February 2020. We found that most participants (64%) lived in households that sustained damage during Cyclone Idai. The overall malaria prevalence was 31% measured by rapid diagnostic test (RDT). When controlling for confounding variables, the odds of malaria infection was nearly threefold higher in participants who lived in households damaged by Cyclone Idai nearly a year after the storm. This highlights the need for long-term disaster response to improve the efficiency and success of malaria control efforts.

Association of anthelmintic treatment with malaria prevalence in Rural Sussundenga, Mozambique.

Background: Mozambique has the 4 th highest malaria incidence and mortality globally. Despite the existing malaria control strategies, malaria prevalence remains stagnant. These challenges have increased calls for innovative strategies in areas with the highest disease burden. Community mass treatment with anthelmintic agents have been used as an effective tool for the control of major helminth infections and has emerged as a potential tool for vector control in the fight against malaria. Methods: This was an analysis of data from a cross-sectional community-based survey designed to study malaria risk, prevention, and health seeking behaviors in Sussundenga, Mozambique. Using logistic regression models, we quantified the association between ever receiving anthelmintic treatment and P. falciparum infection. We also fit models to determine the association between recent anthelmintic treatment and malaria infection. Results: Two-hundred, seventy-seven (277) participants from 83 households were included in this analysis. The prevalence of P. falciparum infection measured by rapid diagnostic test (RDT) was 30%. 77% of participants reported having ever received anthelmintics. The prevalence of malaria was slightly higher among participants who reported ever taking anthelmintics. There was no statistically significant association between prior receipt of anthelmintic and P. falciparum malaria infection after adjusting for age, ITN use and head of household full-time employment (OR = 1.37, 95% CI, 0.70-2.70, p = 0.36). However, recent intake of anthelmintics was associated with lower odds of testing positive for in the adjusted models (OR = 0.35, 95% CI, 0.07-1.80, p = 0.21), but this was not statistically significant. Conclusions: Our findings show that the benefit of anthelmintics treatment as a control tool for P. falciparum malaria infection is likely tied to when it is administered rather than if it was ever administered. These findings offer evidence for making decisions in planning mass community deworming in sub-Saharan Africa.

High burden of malaria among Malawian adults on antiretroviral therapy after discontinuing prophylaxis.

OBJECTIVE: Many individuals living with the human immunodeficiency virus (HIV) infection and receiving antiretroviral therapy (ART) reside in areas at high risk for malaria but how malaria affects clinical outcomes is not well described in this population. We evaluated the burden of malaria infection and clinical malaria, and impact on HIV viral load and CD4 + cell count among adults on ART. DESIGN: We recruited Malawian adults on ART who had an undetectable viral load and ≥250 CD4 +  cells/µl to participate in this randomized trial to continue daily trimethoprim-sulfamethoxazole (TS), discontinue daily co-trimoxazole, or switch to weekly chloroquine (CQ). METHODS: We defined clinical malaria as symptoms consistent with malaria and positive blood smear, and malaria infection as Plasmodium falciparum DNA detected from dried blood spots (collected every 4-12 weeks). CD4 + cell count and viral load were measured every 24 weeks. We used Poisson regression and survival analysis to compare the incidence of malaria infection and clinical malaria. Clinicaltrials.gov NCT01650558. RESULTS: Among 1499 participants enrolled, clinical malaria incidence was 21.4/100 person-years of observation (PYO), 2.4/100 PYO and 1.9/100 PYO in the no prophylaxis, TS, and CQ arms, respectively. We identified twelve cases of malaria that led to hospitalization and all individuals recovered. The preventive effect of staying on prophylaxis was approximately 90% compared to no prophylaxis (TS: incidence rate ratio [IRR] 0.11, 95% confidence interval [CI] 0.08, 0.15 and CQ: IRR 0.09, 95% CI 0.06, 0.13). P. falciparum infection prevalence among all visits was 187/1475 (12.7%), 48/1563 (3.1%), and 29/1561 (1.9%) in the no prophylaxis, TS, and CQ arms, respectively. Malaria infection and clinical malaria were not associated with changes in CD4 + cell count or viral load. CONCLUSION: In clinically stable adults living with HIV on ART, clinical malaria was common after chemoprophylaxis stopped. However, neither malaria infection nor clinical illness appeared to affect HIV disease progression.