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.

Household structure is independently associated with malaria risk in rural Sussundenga, Mozambique.

Introduction: Mozambique has the fourth highest malaria cases and malaria mortality globally. Locally, malaria incidence increases from low in the southern region to high in the central and northern regions. Manica Province in central Mozambique has the fourth highest prevalence of malaria out of the 11 provinces, and the highest in the central region of the country. In this area where coverage of interventions has been limited, household level risk factors can be important for understanding the natural history of infection, as well as the implementation of current and future interventions. There has been indication that the relationship between household structure and malaria risk is actually a mediating one between the true relationship between household income and education and Plasmodium falciparum infection. The objective of this study was to determine and quantify these complex relationships. Methods: We conducted a community-based cross-sectional study in Sussundenga village. Sussundenga is a rural village, located in Sussundenga District, Manica Province, Mozambique. We enrolled 303 participants from 83 randomly selected households. We collected information on demographics, household construction, and administered a P. falciparum rapid diagnostic test (RDT). We constructed several generalized estimating equations logistic regression models to determine the independent effects of housing construction on malaria risk. We also constructed models separate from generalized estimating equations logistic mediation models to determine the proportion of effects mediated by household construction material in the relationship between head of household occupation and education and malaria risk. Results: The overall malaria prevalence among the study population by RDT was 30.8%. In the multivariable model adjusting for all individual and household factors as potential confounders, rudimentary roof structure was the only household structural variable that was statistically significantly associated with increased malaria risk [OR 2.41 (1.03-5.63)]. We found no evidence that household structure mediated the relationship between head of household education or employment and malaria risk in our study population. Discussion: Household structure was a significant risk factor for malaria infection in our study population. These findings are consistent with malaria being a disease of poverty and an area that could be targeted for future interventions that could have long-term impacts.

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.

Modelling sociodemographic factors that affect malaria prevalence in Sussundenga, Mozambique: a cross-sectional study.

Background: Malaria is still one of the leading causes of mortality and morbidity in Mozambique with little progress in malaria control over the past 20 years. Sussundenga is one of most affected areas. Malaria transmission has a strong association with environmental and sociodemographic factors. The knowledge of sociodemographic factors that affects malaria, may be used to improve the strategic planning for its control. Currently such studies have not been performed in Sussundenga. Thus, the objective of this study is to model the relationship between malaria and sociodemographic factors in Sussundenga, Mozambique. Methods: Houses in the study area were digitalized and enumerated using Google Earth Pro version 7.3. In this study 100 houses were randomly selected to conduct a community survey of Plasmodiumfalciparum parasite prevalence using rapid diagnostic test (RDT). During the survey, a questionnaire was conducted to assess the sociodemographic factors of the participants. Descriptive statistics were analyzed and backward stepwise logistic regression was performed establishing a relationship between positive cases and the factors. The analysis was carried out using SPSS version 20 package. Results: The overall P. falciparum prevalence was 31.6%. Half of the malaria positive cases occurred in age group 5 to 14 years. Previous malaria treatment, population density and age group were significant predictors for the model. The model explained 13.5% of the variance in malaria positive cases and sensitivity of the final model was 73.3%. Conclusion: In this area the highest burden of P. falciparum infection was among those aged 5-14 years old. Malaria infection was related to sociodemographic factors. Targeting malaria control at community level can combat the disease more effectively than waiting for cases at health centers. These finding can be used to guide more effective interventions in this region.

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.

Malaria Temporal Variation and Modelling Using Time-Series in Sussundenga District, Mozambique.

Malaria is one of the leading causes of morbidity and mortality in Mozambique, which has the fifth highest prevalence in the world. Sussundenga District in Manica Province has documented high P. falciparum incidence at the local rural health center (RHC). This study's objective was to analyze the P. falciparum temporal variation and model its pattern in Sussundenga District, Mozambique. Data from weekly epidemiological bulletins (BES) was collected from 2015 to 2019 and a time-series analysis was applied. For temporal modeling, a Box-Jenkins method was used with an autoregressive integrated moving average (ARIMA). Over the study period, 372,498 cases of P. falciparum were recorded in Sussundenga. There were weekly and yearly variations in incidence overall (p < 0.001). Children under five years had decreased malaria tendency, while patients over five years had an increased tendency. The ARIMA (2,2,1) (1,1,1) 52 model presented the least Root Mean Square being the most appropriate for forecasting. The goodness of fit was 68.15% for malaria patients less than five years old and 73.2% for malaria patients over five years old. The findings indicate that cases are decreasing among individuals less than five years and are increasing slightly in those older than five years. The P. falciparum case occurrence has a weekly temporal pattern peaking during the wet season. Based on the spatial and temporal distribution using ARIMA modelling, more efficient strategies that target this seasonality can be implemented to reduce the overall malaria burden in both Sussundenga District and regionally.

Mapping Risk of Malaria as a Function of Anthropic and Environmental Conditions in Sussundenga Village, Mozambique.

Mozambique is a country in Southern Africa with around 30 million inhabitants. Malaria is the leading cause of mortality in the country. According to the WHO, Mozambique has the third highest number of malaria cases in the world, representing approximately 5% of the world total cases. Sussundenga District has the highest incidence in the Manica province and environmental conditions are the major contributor to malaria transmission. There is a lack of malaria risk maps to inform transmission dynamics in Sussundenga village. This study develops a malaria risk map for Sussundenga Village in Mozambique and identifies high risk areas to inform on appropriate malaria control and eradication efforts. One hundred houses were randomly sampled and tested for malaria in Sussundenga Rural Municipality. To construct the map, a spatial conceptual model was used to estimate risk areas using ten environmental and anthropic factors. Data from Worldclim, 30 × 30 Landsat images were used, and layers were produced in a raster data set. Layers between class values were compared by assigning numerical values to the classes within each layer of the map with equal rank. Data set input was classified, using diverse weights depending on their appropriateness. The reclassified data outputs were combined after reclassification. The map indicated a high risk for malaria in the northeast and southeast, that is, the neighborhoods of Nhamazara, Nhamarenza, and Unidade. The central eastern areas, that is, 25 de Junho, 1 and 2, 7 de Abril, and Chicueu presented a moderate risk. In Sussundenga village there was 92% moderate and 8% high risk. High malaria risk areas are most often located in densely populated areas and areas close to water bodies. The relevant findings of this study can inform on effective malaria interventions.

Impact of Multiplicity of Plasmodium falciparum Infection on Clinical Disease in Malawi.

Multiplicity of infection (MOI), the number of unique Plasmodium falciparum parasite genotypes found in one infected individual, may contribute to the development of clinical malaria disease. However, the independent contribution of MOI and parasite density to clinical disease has not been well characterized. We conducted a two-year longitudinal cohort study of adults and children in a high-transmission setting in Malawi to test the hypothesis that increased MOI was independently associated with clinical disease, after accounting for parasite density. Of 1,062 episodes of infection, 477 (44.9%) were associated with symptoms. After controlling for repeated measures within an individual, key demographic factors, and parasite density, there was no association between MOI and clinical disease (OR = 1.02, 95% CI: 0.70-1.51). Although the limited ability to discern MOI in low-density asymptomatic infections may have impacted our results, we conclude that MOI is not an independent risk factor for clinical disease.

Anemia in pregnancy in Western Jamaica.

BACKGROUND: Anemia is one of the most prevalent problems in pregnancy. In 2011, 29.9% of all pregnant women in Jamaica were diagnosed with anemia. OBJECTIVE: The objective of this study was to determine the prevalence and predictors of anemia in pregnancy in Western Jamaica. METHODS: A cross-sectional study was conducted among 293 mothers attending post-natal clinics in Western Jamaica. A questionnaire was administered to the mothers, and an abstraction form was used to collect clinical data from the mothers' records. RESULTS: The prevalence of anemia among the women was 37.6%. Younger mothers (aged 18-24 years) were more likely to be anemic compared to those ≥35 years (odds ratio [OR]: 3.44, 95% CI: 1.07-11.06). Mothers who reported not always washing their hands after using the toilet were almost 10 times more likely to be anemic (OR: 9.7, 95% CI: 1.72-54.78) compared to those who reported always washing their hands. Mothers who attended a public facility for antenatal care were 2.3 times more likely to be anemic (OR: 2.31, 95% CI: 1.03-5.18) compared to those who obtained care at a private facility, and mothers who reported being told that they were anemic by a health care provider (HCP) were almost six times more likely to be anemic compared with those who were not told (OR: 5.58, 95% CI: 1.73-17.93). CONCLUSION: The results of the study indicate that early identification and treatment of anemia, especially among younger pregnant women, should be a priority. HCP should ensure that women understand the need to be cured of their anemia and to adhere to preventive hygienic practices.