Feasibility, safety, and impact of the RTS,S/AS01E malaria vaccine when implemented through national immunisation programmes: evaluation of cluster-randomised introduction of the vaccine in Ghana, Kenya, and Malawi.

BACKGROUND: The RTS,S/AS01E malaria vaccine (RTS,S) was introduced by national immunisation programmes in Ghana, Kenya, and Malawi in 2019 in large-scale pilot schemes. We aimed to address questions about feasibility and impact, and to assess safety signals that had been observed in the phase 3 trial that included an excess of meningitis and cerebral malaria cases in RTS,S recipients, and the possibility of an excess of deaths among girls who received RTS,S than in controls, to inform decisions about wider use. METHODS: In this prospective evaluation, 158 geographical clusters (66 districts in Ghana; 46 sub-counties in Kenya; and 46 groups of immunisation clinic catchment areas in Malawi) were randomly assigned to early or delayed introduction of RTS,S, with three doses to be administered between the ages of 5 months and 9 months and a fourth dose at the age of approximately 2 years. Primary outcomes of the evaluation, planned over 4 years, were mortality from all causes except injury (impact), hospital admission with severe malaria (impact), hospital admission with meningitis or cerebral malaria (safety), deaths in girls compared with boys (safety), and vaccination coverage (feasibility). Mortality was monitored in children aged 1-59 months throughout the pilot areas. Surveillance for meningitis and severe malaria was established in eight sentinel hospitals in Ghana, six in Kenya, and four in Malawi. Vaccine uptake was measured in surveys of children aged 12-23 months about 18 months after vaccine introduction. We estimated that sufficient data would have accrued after 24 months to evaluate each of the safety signals and the impact on severe malaria in a pooled analysis of the data from the three countries. We estimated incidence rate ratios (IRRs) by comparing the ratio of the number of events in children age-eligible to have received at least one dose of the vaccine (for safety outcomes), or age-eligible to have received three doses (for impact outcomes), to that in non-eligible age groups in implementation areas with the equivalent ratio in comparison areas. To establish whether there was evidence of a difference between girls and boys in the vaccine's impact on mortality, the female-to-male mortality ratio in age groups eligible to receive the vaccine (relative to the ratio in non-eligible children) was compared between implementation and comparison areas. Preliminary findings contributed to WHO's recommendation in 2021 for widespread use of RTS,S in areas of moderate-to-high malaria transmission. FINDINGS: By April 30, 2021, 652 673 children had received at least one dose of RTS,S and 494 745 children had received three doses. Coverage of the first dose was 76% in Ghana, 79% in Kenya, and 73% in Malawi, and coverage of the third dose was 66% in Ghana, 62% in Kenya, and 62% in Malawi. 26 285 children aged 1-59 months were admitted to sentinel hospitals and 13 198 deaths were reported through mortality surveillance. Among children eligible to have received at least one dose of RTS,S, there was no evidence of an excess of meningitis or cerebral malaria cases in implementation areas compared with comparison areas (hospital admission with meningitis: IRR 0·63 [95% CI 0·22-1·79]; hospital admission with cerebral malaria: IRR 1·03 [95% CI 0·61-1·74]). The impact of RTS,S introduction on mortality was similar for girls and boys (relative mortality ratio 1·03 [95% CI 0·88-1·21]). Among children eligible for three vaccine doses, RTS,S introduction was associated with a 32% reduction (95% CI 5-51%) in hospital admission with severe malaria, and a 9% reduction (95% CI 0-18%) in all-cause mortality (excluding injury). INTERPRETATION: In the first 2 years of implementation of RTS,S, the three primary doses were effectively deployed through national immunisation programmes. There was no evidence of the safety signals that had been observed in the phase 3 trial, and introduction of the vaccine was associated with substantial reductions in hospital admission with severe malaria. Evaluation continues to assess the impact of four doses of RTS,S. FUNDING: Gavi, the Vaccine Alliance; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and Unitaid.

Malaria Burden Stratification in Malawi- A report of a consultative workshop to inform the 2023-2030 Malawi Malaria Strategic Plan.

Background: Malawi's National Malaria Control Programme (NMCP) is developing a new strategic plan for 2023-2030 to combat malaria and recognizes that a blanket approach to malaria interventions is no longer feasible. To inform this new strategy, the NMCP set up a task force comprising 18 members from various sectors, which convened a meeting to stratify the malaria burden in Malawi and recommend interventions for each stratum. Methods: The burden stratification workshop took place from November 29 to December 2, 2022, in Blantyre, Malawi, and collated essential data on malaria burden indicators, such as incidence, prevalence, and mortality. Workshop participants reviewed the malaria burden and intervention coverage data to describe the current status and identified the districts as a appropriate administrative level for stratification and action. Two scenarios were developed for the stratification, based on composites of three variables. Scenario 1 included incidence, prevalence, and under-five all-cause mortality, while Scenario 2 included total malaria cases, prevalence, and under-five all-cause mortality counts. The task force developed four burden strata (highest, high, moderate, and low) for each scenario, resulting in a final list of districts assigned to each stratum. Results: The task force concluded with 10 districts in the highest-burden stratum (Nkhotakota, Salima, Mchinji, Dowa, Ntchisi, Mwanza, Likoma, Lilongwe, Kasungu and Mangochi) 11 districts in the high burden stratum (Chitipa, Rumphi, Nkhata Bay, Dedza, Ntcheu, Neno, Thyolo, Nsanje, Zomba, Mzimba and Mulanje) and seven districts in the moderate burden stratum (Karonga, Chikwawa, Balaka, Machinga, Phalombe, Blantyre, and Chiradzulu). There were no districts in the low-burden stratum. Conclusion: The next steps for the NMCP are to review context-specific issues driving malaria transmission and recommend interventions for each stratum. Overall, this burden stratification workshop provides a critical foundation for developing a successful malaria strategic plan for Malawi.

Prompt treatment-seeking behaviour varies within communities among guardians of children with malaria-related fever in Malawi.

BACKGROUND: In Malawi, malaria is responsible for 40% of hospital deaths. Prompt diagnosis and effective treatment within 24 h of fever onset is critical to prevent progression from uncomplicated to severe disease and to reduce transmission. METHODS: As part of the large evaluation of the malaria vaccine implementation programme (MVIP), this study analysed survey data to investigate whether prompt treatment-seeking behaviour is clustered at community-level according to socio-economic demographics. RESULTS: From 4563 households included in the survey, 4856 children aged 5-48 months were enrolled. Out of 4732 children with documented gender, 52.2% were female and 47.8% male. Among the 4856 children, 33.8% reported fever in the two weeks prior to the survey. Fever prevalence was high in communities with low socio-economic status (SES) (38.3% [95% CI: 33.7-43.5%]) and low in areas with high SES (29.8% [95% CI: 25.6-34.2%]). Among children with fever, 648 (39.5%) sought treatment promptly i.e., within 24 h from onset of fever symptoms. Children were more likely to be taken for prompt treatment among guardians with secondary education compared to those without formal education (aOR:1.37, 95% CI: 1.11-3.03); in communities with high compared to low SES [aOR: 2.78, 95% CI: 1.27-6.07]. Children were less likely to be taken for prompt treatment if were in communities far beyond 5 km to health facility than within 5 km [aOR: 0.44, 95% CI: 0.21-0.92]. CONCLUSION: The high heterogeneity in prevalence of fever and levels of prompt treatment-seeking behaviour underscore the need to promote community-level malaria control interventions (such as use of long-lasting insecticide-treated nets (LLINs), indoor residual spraying (IRS), intermittent preventive therapy (IPT), presumptive treatment and education). Programmes aimed at improving treatment-seeking behaviour should consider targeting communities with low SES and those far from health facility.

Two decades of malaria control in Malawi: Geostatistical Analysis of the changing malaria prevalence from 2000-2022.

Background: Malaria remains a public health problem in Malawi and has a serious socio-economic impact on the population. In the past two decades, available malaria control measures have been substantially scaled up, such as insecticide-treated bed nets, artemisinin-based combination therapies, and, more recently, the introduction of the malaria vaccine, the RTS,S/AS01. In this paper, we describe the epidemiology of malaria for the last two decades to understand the past transmission and set the scene for the elimination agenda. Methods: A collation of parasite prevalence surveys conducted between the years 2000 and 2022 was done. A spatio-temporal geostatistical model was fitted to predict the yearly malaria risk for children aged 2-10 years (PfPR 2-10) at 1×1 km spatial resolutions. Parameter estimation was done using the Monte Carlo maximum likelihood method. District-level prevalence estimates adjusted for population are calculated for the years 2000 to 2022. Results: A total of 2,595 sampled unique locations from 2000 to 2022 were identified through the data collation exercise. This represents 70,565 individuals that were sampled in the period. In general, the PfPR2_10 declined over the 22 years. The mean modelled national PfPR2_10 in 2000 was 43.93 % (95% CI:17.9 to 73.8%) and declined to 19.2% (95%CI 7.49 to 37.0%) in 2022. The smoothened estimates of PfPR2_10 indicate that malaria prevalence is very heterogeneous with hotspot areas concentrated on the southern shores of Lake Malawi and the country's central region. Conclusions: The last two decades are associated with a decline in malaria prevalence, highly likely associated with the scale-up of control interventions. The country should move towards targeted malaria control approaches informed by surveillance data.

In Malawi, malaria continues to be a significant health issue, affecting people's well-being and the economy. Over the past twenty years, efforts to control malaria, such as using bed nets, specific medications, and introducing a malaria vaccine, have increased substantially. This paper explores malaria transmission patterns during this time to better understand the past situation and prepare for future efforts to eliminate the disease. We collected and analyzed data from various surveys conducted between 2000 and 2022, focusing on malaria risk for children aged 2­10 years. We used a detailed statistical model to predict yearly malaria risk. The results show a decline in malaria prevalence over the 22 years. The analysis also reveals variations in malaria prevalence, with hotspot areas particularly concentrated in the southern shores of Lake Malawi and the country's central region. This decline in malaria prevalence is likely linked to the increased implementation of control measures. The findings emphasize the importance of targeted approaches informed by ongoing surveillance data for continued progress in malaria control.

Overdiagnosis of Malaria Illness in an Endemic Setting: A Facility-Based Surveillance Study in Malawi.

In endemic settings where asymptomatic malaria infections are common, malaria infection can complicate fever diagnosis. Factors influencing fever misdiagnosis, including accuracy of malaria rapid diagnostic tests (mRDTs) and the malaria-attributable fraction of fevers (MAF), require further investigation. We conducted facility-based surveillance in Malawi, from January 2012 through December 2013 in settings of high perennial (Chikhwawa), high seasonal (Thoylo), and moderate seasonal (Ndirande) malaria transmission. Consecutive patients presenting to outpatient departments were screened; those with suspected malaria illness were tested by mRDT or routine thick-smear microscopy. Test positivity rates (TPRs), positive predictive value (PPVs) of mRDTs, and MAFs were calculated by site, age, and season. Of 41,471 patients, 10,052 (24.2%) tested positive for malaria. The TPR was significantly greater in Chikhwawa (29.9%; 95% CI, 28.6-30.0) compared with Thyolo (13.2%; 95% CI, 12.5-13.7) and Ndirande (13.1%; 95% CI, 12.2-14.4). The overall PPV was 77.8% (95% CI, 76.8-78.7); it was lowest among infants (69.9%; 95% CI, 65.5-74.2) and highest among school-age children (81.9%; 95% CI, 80.3-83.4). Malaria infection accounted for about 50% of fevers in children younger than 5 years old with microscopy-confirmed Plasmodium falciparum infection, and less than 20% of such fevers in school-age children. Outpatient settings in Malawi had a high burden of malaria illness, but also possible overdiagnosis of malaria illness. Interventions to reduce malaria transmission and rapid testing for other common febrile illness may improve diagnostic clarity among outpatients in malaria endemic settings.

Population Attributable Fraction of Anemia Associated with Plasmodium falciparum Infection in Children in Southern Malawi.

Anemia is a leading cause of morbidity in sub-Saharan Africa. The etiologies of anemia are multifactorial, and it is unclear what proportion of anemia is attributable to malaria in children of different ages in Malawi. We evaluated the population attributable fraction (PAF) of anemia due to malaria using multiple cross-sectional surveys in southern Malawi. We found a high prevalence of anemia, with the greatest proportion attributable to malaria among school-age children (5-15 years) in the rainy season (PAF = 18.8% [95% CI: 16.3, 21.0], compared with PAF = 5.2% [95% CI: 4.0, 6.2] among young children pooled across season [< 5 years] and PAF = 9.7% [95% CI: 6.5, 12.4] among school-age children in the dry season). Malaria control interventions will likely lead to decreases in anemia, especially among school-age children.

Growth and Neurodevelopment Outcomes in HIV-, Tenofovir-, and Efavirenz-Exposed Breastfed Infants in the PMTCT Option B+ Program in Malawi.

BACKGROUND: Pregnant and breastfeeding women in Option B+ in Malawi received antiretroviral drugs (ARVs) containing efavirenz (EFV) and tenofovir disoproxil fumarate (TDF). However, effects on growth, renal, bone metabolism, and neurodevelopment of long-term exposure to low doses of these drugs through breast milk in HIV-exposed infants are unclear. METHODS: Prospective cohorts of TDF-and-EFV-exposed and TDF-and-EFV-unexposed breastfed infants of HIV-infected and HIV-uninfected mothers in Option B+ were recruited in 2:1 ratio, respectively, followed from birth to 18 months. Infants with low birth weight, premature birth, and congenital abnormalities were excluded. Anthropometrics were assessed at birth, 6 weeks, 3, 6, 12, and 18 months. Neurodevelopment assessments used the Bayley Scales of Infant and Toddler Development III from 6 weeks. Creatinine, alkaline phosphatase, and phosphorus were assessed at 3, 6, and 12 months. RESULTS: Of 260 HIV-and-ARV-exposed and 125 HIV-and-ARV-unexposed infants enrolled at birth, 87% and 57%, 78% and 59%, 77% and 54%, 73% and 51%, and 65% and 43% completed 6-weeks, 3, 6, 12, and 18 months visits, respectively. There were no significant differences in the mean Z-scores for length-for-age, weight-for-age, weight-for-length, mid-upper arm circumference-for-age, and head circumference-for-age between groups except at 6-weeks for length-for-age. No bone fractures occurred. Neurodevelopment outcomes were similar between groups. Of creatinine, alkaline phosphatase, and serum phosphate measurements, 1.7%, 2.6%, and 3.3% reached any toxicity levels grades 1-4, respectively, with no differences between groups. CONCLUSION: Long-term exposure to EFV and TDF through breastfeeding in infants of HIV-infected mothers does not seem to result in significant growth, neurodevelopment, renal, or bone adverse outcomes. Data support safety of breastfeeding through 18 months within the Option B+ program.

Prevalence and Clinical Management of Non-malarial Febrile Illnesses among Outpatients in the Era of Universal Malaria Testing in Malawi.

Increasing access to rapid diagnostic tests for malaria (mRDTs) has raised awareness of the challenges healthcare workers face in managing non-malarial febrile illnesses (NMFIs). We examined NMFI prevalence, clinical diagnoses, and prescribing practices in outpatient clinics across different malaria transmission settings in Malawi. Standardized facility-based malaria surveillance was conducted at three facilities one of every 4 weeks over 2 years. Information on demographics, presenting symptoms, temperature, clinical diagnosis, and treatment were collected from outpatients presenting with malaria-like symptoms. Of the 25,486 patients with fever, 69% had NMFI. Non-malarial febrile illness prevalence was lower in 5- to 15-year-old patients (55%) than in children < 5 years (72%) and adults > 15 years of age (77%). The most common clinical diagnoses among febrile patients with negative mRDTs in all age-groups and settings were respiratory infections (46%), sepsis (29%), gastroenteritis (13%), musculoskeletal pain (9%), and malaria (5%). Antibiotic prescribing was high in all age-groups and settings. Trimethoprim-sulfamethoxazole (40%) and amoxicillin (29%) were the most commonly prescribed antibiotics and were used for nearly all clinical diagnoses. In these settings with minimal access to diagnostic tools, patients with fever and a negative mRDT received a limited number of clinical diagnoses. Many were likely to be inaccurate and were associated with the inappropriate use of the limited range of available antibiotics. Prescription and diagnostic practices for NMFIs in the facilities require research and policy input. Resource-limited malaria-endemic countries urgently need more point-of-care diagnostic tools and evidence-based diagnosis and treatment algorithms to provide effective and cost-efficient care.

Impact of Facility- and Community-Based Peer Support Models on Maternal Uptake and Retention in Malawi's Option B+ HIV Prevention of Mother-to-Child Transmission Program: A 3-Arm Cluster Randomized Controlled Trial (PURE Malawi).

BACKGROUND: Many sub-Saharan African countries have adopted Option B+, a prevention of mother-to-child transmission approach providing HIV-infected pregnant and lactating women with immediate lifelong antiretroviral therapy. High maternal attrition has been observed in Option B+. Peer-based support may improve retention. METHODS: A 3-arm stratified cluster randomized controlled trial was conducted in Malawi to assess whether facility- and community-based peer support would improve Option B+ uptake and retention compared with standard of care (SOC). In SOC, no enhancements were made (control). In facility-based and community-based models, peers provided patient education, support groups, and patient tracing. Uptake was defined as attending a second scheduled follow-up visit. Retention was defined as being alive and in-care at 2 years without defaulting. Attrition was defined as death, default, or stopping antiretroviral therapy. Generalized estimating equations were used to estimate risk differences (RDs) in uptake. Cox proportional hazards regression with shared frailties was used to estimate hazard of attrition. RESULTS: Twenty-one facilities were randomized and enrolled 1269 women: 447, 428, and 394 in facilities that implemented SOC, facility-based, and community-based peer support models, respectively. Mean age was 27 years. Uptake was higher in facility-based (86%; RD: 6%, confidence interval [CI]: -3% to 15%) and community-based (90%; RD: 9%, CI: 1% to 18%) models compared with SOC (81%). At 24 months, retention was higher in facility-based (80%; RD: 13%, CI: 1% to 26%) and community-based (83%; RD: 16%, CI: 3% to 30%) models compared with SOC (66%). CONCLUSIONS: Facility- and community-based peer support interventions can benefit maternal uptake and retention in Option B+.

Viral Suppression and HIV Drug Resistance at 6 Months Among Women in Malawi's Option B+ Program: Results From the PURE Malawi Study.

BACKGROUND: In 2011, Malawi launched Option B+, a program of universal antiretroviral therapy (ART) treatment for pregnant and lactating women to optimize maternal health and prevent pediatric HIV infection. For optimal outcomes, women need to achieve HIVRNA suppression. We report 6-month HIVRNA suppression and HIV drug resistance in the PURE study. METHODS: PURE study was a cluster-randomized controlled trial evaluating 3 strategies for promoting uptake and retention; arm 1: Standard of Care, arm 2: Facility Peer Support, and arm 3: Community Peer support. Pregnant and breastfeeding mothers were enrolled and followed according to Malawi ART guidelines. Dried blood spots for HIVRNA testing were collected at 6 months. Samples with ART failure (HIVRNA ≥1000 copies/ml) had resistance testing. We calculated odds ratios for ART failure using generalized estimating equations with a logit link and binomial distribution. RESULTS: We enrolled 1269 women across 21 sites in Southern and Central Malawi. Most enrolled while pregnant (86%) and were WHO stage 1 (95%). At 6 months, 950/1269 (75%) were retained; 833/950 (88%) had HIVRNA testing conducted, and 699/833 (84%) were suppressed. Among those with HIVRNA ≥1000 copies/ml with successful amplification (N = 55, 41% of all viral loads > 1000 copies/ml), confirmed HIV resistance was found in 35% (19/55), primarily to the nonnucleoside reverse transcriptase inhibitor class of drugs. ART failure was associated with treatment default but not study arm, age, WHO stage, or breastfeeding status. CONCLUSIONS: Virologic suppression at 6 months was <90% target, but the observed confirmed resistance rates suggest that adherence support should be the primary approach for early failure in option B+.

Exploring the Experiences of Women and Health Care Workers in the Context of PMTCT Option B Plus in Malawi.

INTRODUCTION: Malawi has embarked on a "test-and-treat" approach to prevent mother-to-child transmission (PMTCT) of HIV, known as "Option B+," offering all HIV-infected pregnant and breastfeeding women lifelong antiretroviral therapy (ART) regardless of CD4 count or clinical stage. A cross-sectional qualitative study was conducted to explore early experiences surrounding "Option B+" for patients and health care workers (HCWs) in Malawi. METHODS: Study participants were purposively selected across 6 health facilities in 3 regional health zones in Malawi. Semi-structured interviews were conducted with women enrolled in "Option B+" (n = 24), and focus group discussions were conducted with HCWs providing Option B+ services (n = 6 groups of 8 HCWs). Data were analyzed using a qualitative thematic coding framework. RESULTS: Patients and HCWs identified the lack of male involvement as a barrier to retention in care and expressed concerns at the rapidity of the test-and-treat process, which makes it difficult for patients to "digest" a positive diagnosis before starting ART. Fear regarding the breach of privacy and confidentiality were also identified as contributing to loss to follow-up of women initiated under the Option B+. Disclosure remains a difficult process within families and couples. Lifelong ART was also perceived as an opportunity to plan future pregnancies. CONCLUSIONS: As "Option B+" continues to be rolled out, novel interventions to support and retain women into care must be implemented. These include providing space, time, and support to accept a diagnosis before starting ART, engaging partners and families, and addressing the need for peer support and confidentiality.

Incidence and Seasonality of Influenza-Like Illnesses Among Pregnant Women in Blantyre, Malawi.

Pregnant women with influenza infection are at increased risk of developing complications compared with other adults. Information about burden of influenza in pregnant women in Africa is limited. To determine incidence and seasonality of influenza-like illness (ILI) in pregnant women in Blantyre, Malawi, we recruited a cohort of 450 pregnant women and conducted surveillance for ILI and malaria infection. We recorded gestational age and birthweight. We accrued 157 person-years of observation (PYO) and detected 37 episodes of ILI (24/100 PYO) and 83 episodes of malaria infection (including all new episodes of parasitemia) (53/100 PYO). ILI was the most common cause of fever, but was not associated with adverse pregnancy outcomes. ILI incidence peaked during the hot dry season. These results indicate that ILI is a significant burden among Malawian pregnant women and it is somewhat seasonal. Studies with molecular diagnostics are needed to establish influenza-specific burden and the potential role of vaccination.

The value of informal care in the context of option B+ in Malawi: a contingent valuation approach.

BACKGROUND: Informal care, the health care provided by the patient's social network is important in low income settings although its monetary value is rarely estimated. The lack of estimates of the value of informal care has led to its omission in economic evaluations but this can result in incorrect decisions about cost effectiveness of an intervention. We explore the use of contingent valuation methods of willingness to pay (WTP) and willingness to accept (WTA) to estimate the value of informal care provided to HIV infected women that are accessing antiretroviral therapy (ART) under the Option B+ approach to prevention of mother-to-child transmission (PMTCT) of HIV in Malawi. METHODS: We collected cross sectional data from 93 caregivers of women that received ART care from six health facilities in Malawi. Caregivers of women that reported for ART care on the survey day and consented to participate in the survey were included until the targeted sample size for the facility was reached. We estimated the value of informal care by using the willingness to accept (WTA) and willingness to pay (WTP) approaches. Medians were used to summarize the values and these were compared by the Wilcoxon signed-rank test. RESULTS: The median WTA to provide informal care in a month was US$30 and the median WTP for informal care was US$13 and the two were statistically different (p < 0.000). Median WTP was higher in the urban areas than in the rural areas (US$21 vs. US$13, p < 0.001) and for caregivers from households from higher wealth quintile than in the lower quintile (US$15 vs. US$13, p < 0.0462). CONCLUSION: Informal caregivers place substantial value on informal care giving. In low income settings where most caregivers are not formally employed, WTP and WTA approaches can be used to value informal care. CLINICAL TRIAL NUMBER: NCT02005835.

Bed net use among school-aged children after a universal bed net campaign in Malawi.

BACKGROUND: Recent data from Malawi suggest that school-aged children (SAC), aged 5-15 years, have the highest prevalence of Plasmodium falciparum infection among all age groups. They are the least likely group to utilize insecticide-treated nets (ITNs), the most commonly available intervention to prevent malaria in Africa. This study examined the effects of a universal ITN distribution campaign, and their durability over time in SAC in Malawi. This study identified factors that influence net usage among SAC and how these factors changed over time. METHODS: Cross-sectional surveys using cluster random sampling were conducted at the end of each rainy and dry season in southern Malawi from 2012 to 2014; six surveys were done in total. Mass net distribution occurred between the first and second surveys. Data were collected on household and individual net usage as well as demographic information. Statistical analyses used generalized linear mixed models to account for clustering at the household and neighbourhood level. RESULTS: There were 7347 observations from SAC and 14,785 from young children and adults. SAC used nets significantly less frequently than the rest of the population (odds ratio (OR) from 0.14 to 0.38). The most important predictors of net usage among SAC were a lower ratio of people to nets in a household and higher proportion of nets that were hanging at the time of survey. Older SAC (11-15 years) were significantly less likely to use nets than younger SAC (5-10 years) [OR = 0.24 (95 % CI: 0.21, 0.28)]. The universal bed net campaign led to a statistically significant population-wide increase in net use, however net use returned to near baseline within 3 years. CONCLUSIONS: This study suggests that a single universal net distribution campaign, in combination with routine distribution through health clinics is not sufficient to cause a sustained increase in net usage among SAC. Novel approaches to ITN distribution, such as school-based distribution, may be needed to address the high prevalence of infection in SAC.

The effect of local variation in malaria transmission on the prevalence of sulfadoxine-pyrimethamine resistant haplotypes and selective sweep characteristics in Malawi.

BACKGROUND: Persistence of sulfadoxine-pyrimethamine (SP) resistance has been described in an urban setting in Malawi where malaria transmission is relatively low. Higher malaria transmission is associated with greater genetic diversity and more frequent genetic recombination, which could lead to a more rapid re-emergence of SP-sensitive parasites, as well as more rapid degradation of selective sweeps. In this study, the impact of local variation in malaria transmission on the prevalence of SP-resistant haplotypes and selective sweep characteristics was investigated at an urban site with low parasite prevalence and two rural sites with moderate and high parasite prevalence. METHODS: Samples from three sites with different parasite prevalence were genotyped for resistance markers within pfdhfr-ts and pfdhps and at microsatellites flanking these genes. Expected heterozygosity (He) was estimated to evaluate genetic diversity. RESULTS: No difference in the prevalence of highly resistant DHFR 51I/59R/108N and DHPS 437G/540E was found between sites. Small differences in He flanking pfdhfr-ts and pfdhps were seen between rural-moderate and the other sites, as well as some shared haplotypes between the rural-high and urban-low sites. CONCLUSIONS: The results do not show an effect of local variation in malaria transmission, as inferred from parasite prevalence, on SP-resistant haplotype prevalence.

School-Age Children Are a Reservoir of Malaria Infection in Malawi.

UNLABELLED: Malaria surveillance and interventions in endemic countries often target young children at highest risk of malaria morbidity and mortality. We aimed to determine whether school-age children and adults not captured in surveillance serve as a reservoir for malaria infection and may contribute to malaria transmission. Cross-sectional surveys were conducted in one rainy and one dry season in southern Malawi. Demographic and health information was collected for all household members. Blood samples were obtained for microscopic and PCR identification of Plasmodium falciparum. Among 5796 individuals aged greater than six months, PCR prevalence of malaria infection was 5%, 10%, and 20% in dry, and 9%, 15%, and 32% in rainy seasons in Blantyre, Thyolo, and Chikhwawa, respectively. Over 88% of those infected were asymptomatic. Participants aged 6-15 years were at higher risk of infection (OR=4.8; 95%CI, 4.0-5.8) and asymptomatic infection (OR=4.2; 95%CI, 2.7-6.6) than younger children in all settings. School-age children used bednets less frequently than other age groups. Compared to young children, school-age children were brought less often for treatment and more often to unreliable treatment sources. CONCLUSION: School-age children represent an underappreciated reservoir of malaria infection and have less exposure to antimalarial interventions. Malaria control and elimination strategies may need to expand to include this age group.

Improving PMTCT uptake and retention services through novel approaches in peer-based family-supported care in the clinic and community: a 3-arm cluster randomized trial (PURE Malawi).

In July 2011, Malawi introduced an ambitious public health program known as "Option B+," which provides all HIV-infected pregnant and breastfeeding women with lifelong combination antiretroviral therapy, regardless of clinical stage or CD4 count. Option B+ is expected to have benefits for HIV-infected women, their HIV-exposed infants, and their HIV-uninfected male sex partners. However, these benefits hinge on early uptake of prevention of mother-to-child transmission, good adherence, and long-term retention in care. The Prevention of mother-to-child transmission Uptake and REtention (PURE) study is a 3-arm cluster randomized controlled trial to evaluate whether clinic- or community-based peer support will improve care-seeking and retention in care by HIV-infected pregnant and breastfeeding women, their HIV-exposed infants, and their male sex partners, and ultimately improve health outcomes in all 3 populations. We describe the PURE Malawi Consortium, the initial work conducted to inform the trial and interventions, the trial design, and the analysis plan. We then discuss concerns and expected contributions to Malawi and the region.

Marked reduction in prevalence of malaria parasitemia and anemia in HIV-infected pregnant women taking cotrimoxazole with or without sulfadoxine-pyrimethamine intermittent preventive therapy during pregnancy in Malawi.

BACKGROUND: Effectiveness of cotrimoxazole (CTX) compared with sulfadoxine-pyrimethamine (SP) intermittent-preventive-therapy (IPTp) for malaria in HIV-infected pregnant women is unknown. We examined effectiveness of CTX with or without SP-IPTp versus SP-IPTp at reducing malaria parasitemia and anemia. METHODS: From 2005 to 2009, we conducted a cross-sectional study of HIV-infected pregnant women at Thyolo Hospital, Malawi. Blood was tested for malaria parasitemia and anemia (hemoglobin<11 g/dl). Data were collected on use of anti-malaria interventions and other risk factors. CTX prophylaxis policy for HIV-infected pregnant women was introduced in 2007, but implementation problems resulted in some women receiving both CTX and SP-IPTp. FINDINGS: We enrolled 1,142 women, of whom 1,121 had data on CTX and/or SP-IPTp intake. Of these, 49.7%, 29.8%, and 15.4% reported taking SP-IPTp only, CTX only and SP-IPTp plus CTX, respectively. Compared with women taking SP-IPTp, those taking SP-IPTp plus CTX and CTX were less likely to have malaria parasitemia (OR, [95%CI]: 0.09, [0.01-0.66] and 0.43, [0.19-0.97], respectively) or anemia (PR, [95% CI]: 0.67, [0.54-0.83] and 0.72, [0.61-0.83], respectively). CONCLUSION: In HIV-infected pregnant women, daily CTX was associated with reduced malaria parasitemia and anemia compared with SP-IPTp. CTX plus SP-IPTp was associated with further reduction in malaria parasitemia but toxicity was not fully assessed.

Prevalence distribution and risk factors for Schistosoma hematobium infection among school children in Blantyre, Malawi.

BACKGROUND: Schistosomiasis is a public health problem in Malawi but estimates of its prevalence vary widely. There is need for updated information on the extent of disease burden, communities at risk and factors associated with infection at the district and sub-district level to facilitate effective prioritization and monitoring while ensuring ownership and sustainability of prevention and control programs at the local level. METHODS AND FINDINGS: We conducted a cross-sectional study between May and July 2006 among pupils in Blantyre district from a stratified random sample of 23 primary schools. Information on socio-demographic factors, schistosomiasis symptoms and other risk factors was obtained using questionnaires. Urine samples were examined for Schistosoma hematobium ova using filtration method. Bivariate and multiple logistic regressions with robust estimates were used to assess risk factors for S. hematobium. One thousand one hundred and fifty (1,150) pupils were enrolled with a mean age of 10.5 years and 51.5% of them were boys. One thousand one hundred and thirty-nine (1,139) pupils submitted urine and S. hematobium ova were detected in 10.4% (95%CI 5.43-15.41%). Male gender (OR 1.81; 95% CI 1.06-3.07), child's knowledge of an existing open water source (includes river, dam, springs, lake, etc.) in the area (OR 1.90; 95% CI 1.14-3.46), history of urinary schistosomiasis in the past month (OR 3.65; 95% CI 2.22-6.00), distance of less than 1 km from school to the nearest open water source (OR 5.39; 95% CI 1.67-17.42) and age 8-10 years (OR 4.55; 95% CI 1.53-13.50) compared to those 14 years or older were associated with infection. Using urine microscopy as a gold standard, the sensitivity and specificity of self-reported hematuria was 68.3% and 73.6%, respectively. However, the positive predictive value was low at 23.9% and was associated with age. CONCLUSION: The study provides an important update on the status of infection in this part of sub-Saharan Africa and exemplifies the success of deliberate national efforts to advance active participation in schistosomiasis prevention and control activities at the sub-national or sub-district levels. In this population, children who attend schools close to open water sources are at an increased risk of infection and self-reported hematuria may still be useful in older children in this region.