Dyson Mwandama

Adherence to Treatment With Artemether-Lumefantrine for Uncomplicated Malaria in Rural Malawi

BACKGROUND In 2007, Malawi replaced the first-line medication for uncomplicated malaria, sulfadoxine-pyrimethamine-a single-dose regimen-with artemether-lumefantrine (AL)-a 6-dose, 3-day regimen. Because of concerns about the complex dosing schedule, we assessed patient adherence to AL 2 years after routine implementation. METHODS Adults and children with uncomplicated malaria were recruited at 3 health centers. We conducted both pill counts and in-home interviews on medication consumption 72 hours after patients received AL. Complete adherence was defined as correctly taking all 6 AL doses, as assessed by pill count and dose recall. We used logistic regression to identify factors associated with complete adherence. RESULTS Of 386 patients, 65% were completely adherent. Patients were significantly more likely to be completely adherent if they received their first dose of AL as directly observed therapy at the health center (odds ratio [OR], 2.4; P < .01), received instructions using the medication package as a visual aid (OR, 2.5; P = .02), and preferred AL over other antimalarials (OR, 2.7; P < .001). In contrast, children <5 years of age were significantly less likely to be adherent (OR, 0.5; P = .05). CONCLUSIONS Adherence to AL treatment for uncomplicated malaria was moderate, and children, who are the most likely to die of malaria, were less adherent than adults. Efforts to improve adherence should be focused on this vulnerable group. Interventions including the introduction of child-friendly antimalarial formulations, direct observation of the first dose, use of the AL package as a visual aid for instructions, and enhancing patient preference for AL could potentially increase AL adherence and overall effectiveness.

Effectiveness of Intermittent Preventive Treatment With Sulfadoxine-Pyrimethamine During Pregnancy on Maternal and Birth Outcomes in Machinga District, Malawi

BACKGROUND Malaria during pregnancy is associated with low birth weight and increased perinatal mortality, especially among primigravidae. Despite increasing prevalence of malarial parasite resistance to sulfadoxine-pyrimethamine (SP), SP continues to be recommended for intermittent preventive treatment in pregnancy (IPTp). METHODS Women without human immunodeficiency virus infection were enrolled upon delivery. Data on the number of SP doses received during pregnancy were recorded. The primary outcome was placental infection demonstrated by histologic analysis. Secondary outcomes included malaria parasitemia (in peripheral, placental, cord blood specimens) at delivery and composite birth outcome (small for gestational age, preterm delivery, or low birth weight). RESULTS.: Of 703 women enrolled, 22% received <2 SP doses. Receipt of ≥ 2 SP doses had no impact on histologically confirmed placental infection. IPTp-SP was associated with a dose-dependent protective effect on composite birth outcome in primigravidae, with an adjusted prevalence ratio of 0.50 (95% confidence interval [CI], .30-.82), 0.30 (95% CI, .19-.48), and 0.18 (95% CI, .05-.61) for 1, 2, and ≥ 3 doses, respectively, compared with 0 doses. CONCLUSIONS IPTp-SP did not reduce the frequency of placental infection but was associated with improved birth outcomes. Few women received no SP, so the true effect of IPTp-SP may be underestimated. Malawian pregnant women should continue to receive IPTp-SP, but alternative strategies and antimalarials for preventing malaria during pregnancy should be investigated.

The A581G Mutation in the Gene Encoding Plasmodium falciparum Dihydropteroate Synthetase Reduces the Effectiveness of Sulfadoxine-Pyrimethamine Preventive Therapy in Malawian Pregnant Women

BACKGROUND The A581 G: mutation in the gene encoding Plasmodium falciparum dihydropteroate synthase (dhps), in combination with the quintuple mutant involving mutations in both dhps and the gene encoding dihydrofolate reductase (dhfr), the so-called sextuple mutant, has been associated with increased placental inflammation and decreased infant birth weight among women receiving intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) during pregnancy. METHODS Between 2009 and 2011, delivering women without human immunodeficiency virus infection were enrolled in an observational study of IPTp-SP effectiveness in Malawi. Parasites were detected by polymerase chain reaction (PCR); positive samples were sequenced to genotype the dhfr and dhps loci. The presence of K540 E: in dhps was used as a marker for the quintuple mutant. RESULTS Samples from 1809 women were analyzed by PCR; 220 (12%) were positive for P. falciparum. A total of 202 specimens were genotyped at codon 581 of dhps; 17 (8.4%) harbored the sextuple mutant. The sextuple mutant was associated with higher risks of patent infection in peripheral blood (adjusted prevalence ratio [aPR], 2.76; 95% confidence interval [CI], 1.82-4.18) and placental blood (aPR 3.28; 95% CI, 1.88-5.78) and higher parasite densities. Recent SP use was not associated with increased parasite densities or placental pathology overall and among women with parasites carrying dhps A581 G: . CONCLUSIONS IPTp-SP failed to inhibit parasite growth but did not exacerbate pathology among women infected with sextuple-mutant parasites. New interventions to prevent malaria during pregnancy are needed urgently.

Impact of Health Facility-Based Insecticide Treated Bednet Distribution in Malawi: Progress and Challenges towards Achieving Universal Coverage

Background High levels of insecticide treated bednet (ITN) use reduce malaria burden in countries with intense transmission such as Malawi. Since 2007 Malawi has implemented free health facility-based ITN distribution for pregnant women and children <5 years old (under-5s). We evaluated the progress of this targeted approach toward achieving universal ITN coverage. Methods We conducted a cross-sectional household survey in eight districts in April 2009. We assessed household ITN possession, ITN use by all household members, and P. falciparum asexual parasitemia and anemia (hemoglobin <11 grams/deciliter) in under-5s. Results We surveyed 7,407 households containing 29,806 persons. Fifty-nine percent of all households (95% confidence interval [95% CI]: 56–62), 67% (95% CI: 64–70) of eligible households (i.e., households with pregnant women or under-5s), and 40% (95% CI: 36–45) of ineligible households owned an ITN. In households with at least one ITN, 76% (95% CI: 74–78) of all household members, 88% (95% CI: 87–90) of under-5s and 90% (95% CI: 85–94) of pregnant women used an ITN the previous night. Of 6,677 ITNs, 92% (95% CI: 90–94) were used the previous night with a mean of 2.4 persons sleeping under each ITN. In multivariable models adjusting for district, socioeconomic status and indoor residual spraying use, ITN use by under-5s was associated with a significant reduction in asexual parasitemia (adjusted odds ratio (aOR) 0.79; 95% CI: 0.64–0.98; p-value 0.03) and anemia (aOR 0.79; 95% CI 0.62–0.99; p-value 0.04). Of potential targeted and non-targeted mass distribution strategies, a campaign distributing 1 ITN per household might increase coverage to 2.1 household members per ITN, and thus achieve near universal coverage often defined as 2 household members per ITN. Conclusions Malawi has substantially increased ITN coverage using health facility-based distribution targeting pregnant women and under-5s, but needs to supplement these activities with non-targeted mass distribution campaigns to achieve universal coverage and maximum public health impact.

Impact of Indoor Residual Spraying with Lambda-Cyhalothrin on Malaria Parasitemia and Anemia Prevalence among Children Less than Five Years of Age in an Area of Intense, Year-Round Transmission in Malawi

Little is known about the impact of indoor residual spraying (IRS) in areas with intense malaria transmission such as sub-Saharan Africa. In Malawi, IRS with lambda-cyhalothrin has been applied annually in an area of intense year-long transmission since 2007. We evaluated the impact of IRS on parasitemia and anemia prevalence in children less than five years of age by using a cross-sectional household survey conducted in 2009, six months after the second IRS spray round. We measured malaria parasitemia and anemia (hemoglobin level < 11 g/dL) in 899 children less than five years of age and used binomial regression to assess the impact of IRS by comparing children living in a household sprayed with IRS (direct IRS) with those in a household not sprayed with IRS, but in an IRS area (indirect IRS) and those living in a household not sprayed with IRS and not in an IRS area (no IRS). In the IRS area, 77% of households reported receiving IRS. Adjusting for bed net use, house construction, and socioeconomic status, we found that receiving direct IRS and indirect IRS were significantly associated with a 33% (95% confidence interval [CI] = 1–54%) and 46% (95% CI = 20–64%) reduction in parasitemia and a 21% (95% CI = 4–34%) and 30% (95% CI = 12–45%) reduction in anemia prevalence, respectively.

Elevated dry-season malaria prevalence associated with fine-scale spatial patterns of environmental risk: a case-control study of children in rural Malawi

BackgroundUnderstanding the role of local environmental risk factors for malaria in holo-endemic, poverty-stricken settings will be critical to more effectively implement- interventions aimed at eventual elimination. Household-level environmental drivers of malaria risk during the dry season were investigated in rural southern Malawi among children < five years old in two neighbouring rural Traditional Authority (TA) regions dominated by small-scale agriculture.MethodsTen villages were randomly selected from TA Sitola (n = 6) and Nsamala (n = 4). Within each village, during June to August 2011, a census was conducted of all households with children under-five and recorded their locations with a geographic position system (GPS) device. At each participating house, a nurse administered a malaria rapid diagnostic test (RDT) to children under five years of age, and a questionnaire to parents. Environmental data were collected for each house, including land cover within 50-m radius. Variables found to be significantly associated with P. falciparum infection status in bivariate analysis were included in generalized linear models, including multivariate logistic regression (MLR) and multi-level multivariate logistic regression (MLLR). Spatial clustering of RDT status, environmental factors, and Pearson residuals from MLR and MLLR were analysed using the Getis-Ord Gi* statistic.ResultsOf 390 children enrolled from six villages in Sitola (n = 162) and four villages in Nsamala (n = 228), 45.6% tested positive (n = 178) for Plasmodium infection by RDT. The MLLR modelled the statistical relationship of Plasmodium positives and household proximity to agriculture (<25-m radius), controlling for the child sex and age (in months), bed net ownership, elevation, and random effects intercepts for village and TA-level unmeasured factors. After controlling for area affects in MLLR, proximity to active agriculture remained a significant predictor of positive RDT result (OR 2.80, 95% CI 1.41-5.55). Mapping of Pearson residuals from MLR showed significant clustering (Gi* z > 2.58, p < 0.01) predominantly within TA Sitola, while residuals from MLLR showed no such clustering.ConclusionThis study provides evidence for significant, dry-season heterogeneity of malaria prevalence strongly linked to peridomestic land use, and particularly of elevated risk associated with nearby crop production.

Pooled PCR testing strategy and prevalence estimation of submicroscopic infections using Bayesian latent class models in pregnant women receiving intermittent preventive treatment at Machinga District Hospital, Malawi, 2010.

BackgroundLow malaria parasite densities in pregnancy are a diagnostic challenge. PCR provides high sensitivity and specificity in detecting low density of parasites, but cost and technical requirements limit its application in resources-limited settings. Pooling samples for PCR detection was explored to estimate prevalence of submicroscopic malaria infection in pregnant women at delivery. Previous work uses gold-standard based methods to calculate sensitivity and specificity of tests, creating a challenge when newer methodologies are substantially more sensitive than the gold standard. Thus prevalence was estimated using Bayesian latent class models (LCMs) in this study.MethodsNested PCR (nPCR) for the 18S rRNA gene subunit of Plasmodium falciparum was conducted to detect malaria infection in microscopy-negative Malawian women on IPTp. Two-step sample pooling used dried blood spot samples (DBSs) collected from placenta or periphery at delivery. Results from nPCR and histology as well as previously published data were used to construct LCMs to estimate assay sensitivity and specificity. Theoretical confidence intervals for prevalence of infection were calculated for two-step and one-step pooling strategies.ResultsOf 617 microscopy-negative Malawian women, 39 (6.3%) were identified as actively infected by histology while 52 (8.4%) were positive by nPCR. One hundred forty (22.7%) individuals had past infection assessed by histology. With histology as a reference, 72% of women in the active infection group, 7.1% in the past infection group and 3.2% in histology-negative group were nPCR positive. Using latent class models without a gold standard, histology had a median sensitivity of 49.7% and specificity of 97.6% for active infection while PCR had a median sensitivity of 96.0% and specificity of 99.1%. The true prevalence of active infection was estimated at 8.0% (CI: 5.8-10.5%) from PCR. PCR also had similar sensitivity for detecting either peripheral or placental malaria for submicroscopic infections. One-step pooling would give similar confidence intervals for pool sizes less than 20 while reducing the number of tests performed.ConclusionsPooled nPCR testing was a sensitive and resource-efficient strategy and LCMs provided precise prevalence estimates of submicroscopic infections. Compared to two-step pooling, one-step pooling could provide similar prevalence estimates at population levels with many fewer tests required.

Home Visits to Assess the Reliability of Caregiver-Reported Use of Insecticide-Treated Bednets by Children in Machinga District, Malawi

A malaria cohort study was conducted among young children in Machinga District, Malawi, following distribution of insecticide-treated bednets (ITNs) in May 2012. To assess ITN use, two independently sampled subsets of children (211 during survey 1 [December 2012-January 2013] and 325 during survey 2 [September-October 2013]) were randomly selected to compare the proportions of positive and negative agreement between caregiver verbal reports at monthly interviews with visual observation of the ITN at home visits. Caregiver-reported ITN use was consistently high during both surveys (98.1% and 96.0%, respectively; P = 0.17). Home visit-based ITN use fell significantly (P < 0.001) from survey 1 (98.6%) to survey 2 (88.6%). The proportions of positive agreement between caregiver report and home visit in the first and second surveys were 98.8% (95% confidence interval [CI] 97.6-99.8%) and 93.3% (95% CI 91.2-95.3%), respectively. The proportions of negative agreement in the first and second surveys were 28.6% (95% CI 0-75.0%) and 20.0% (95% CI 0.1-35.0%), respectively. ITN use by children was high in Machinga District, and caregiver reports and home visits with visual confirmation of the net demonstrated a high level of agreement for use of ITNs, but a low level of agreement when ITNs were not used.