Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-30 (of 116 Records) |
Query Trace: Gutman J[original query] |
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Attractive targeted sugar baits for malaria control in western Kenya (ATSB-Kenya): enrolment characteristics of cohort children and households
Kamau A , Obiet K , Ogwang C , McDermott DP , Lesosky M , Janssen J , Odongo W , Gutman JR , Schultz JS , Nicholas W , Seda B , Chepkirui M , Aduwo F , Towett O , Otieno K , Donnelly MJ , Ochomo E , Kariuki S , Samuels AM , OTer Kuile F , Staedke SG . Malar J 2024 23 (1) 403 BACKGROUND: In western Kenya, a cluster-randomized trial is assessing the impact of attractive targeted sugar baits (ATSBs) on malaria in children enrolled in three consecutive cohorts. Here, characteristics of children and households at enrolment, and factors associated with baseline malaria prevalence are described. METHODS: Children aged 1 to < 15 years were randomly selected by cluster (n = 70) from a census database. Cohorts were enrolled in March-April 2022, September-October 2022, and March-April 2023. ATSBs were deployed in March 2022. At enrolment, all participants were tested for malaria by rapid diagnostic test (RDT). After enrolment a household survey was conducted. Household structures were classified as 'improved' (finished walls and roofs, and closed eaves) or 'traditional' (all other construction). A generalized linear mixed model was used to assess factors associated with malaria prevalence. RESULTS: Of 3705 children screened, 220 declined and 523 were excluded, due to plans to leave the study area (n = 392), ineligible age (n = 64) or other reason (n = 67). Overall, 2962 children were enrolled. Bed net use the previous night was more common in children aged 1-4 years (746/777 [96%]) than those aged 5-<15 years (1806/2157 [84%], p < 0.001). Of the 2644 households surveyed (for 2,886 participants), information on house construction was available for 2595. Of these, only 199 (8%) were categorized as 'improved', as most houses had open eaves. While 99% of households owned at least one bed net, only 51% were adequately covered (one net per two household residents). Among 999 children enrolled in the first cohort (baseline), 498 (50%) tested positive by RDT. In an adjusted multivariable analysis, factors associated with RDT positivity included sub-county (Alego-Usonga vs Rarieda, adjusted odds ratio [aOR] 4.81; 95% CI: 2.74-8.45; p < 0.001), house construction (traditional vs improved, aOR 2.80; 95% CI: 1.59-4.95; p < 0.001), and age (5-< 15 vs 1-4 years, aOR 1.64; 95% CI: 1.13-2.37; p = 0.009). CONCLUSIONS: In western Kenya, the burden of malaria in children remains high. Most households owned a bed net, but coverage was inadequate. Residents of Alego-Usonga sub-county, those living in traditionally constructed households, and older children were more likely to test positive by RDT. Additional tools are needed to effectively control malaria in this area. Trial registration The ATSB trial is registered under Clinicaltrials.gov NCT05219565. |
COVID-19 vaccine uptake and associated risk factors among first antenatal care attendees in Zambia, 2021-2022: A repeated cross-sectional study
Tembo T , Somwe P , Bosomprah S , Heilmann E , Kalenga K , Moyo N , Kabamba B , Seffren V , Fwoloshi S , Rutagwera MR , Musunse M , Mwiinga L , Gutman JR , Hines JZ , Sikazwe I . PLOS Glob Public Health 2024 4 (10) e0003028 Pregnant women are considered a high-risk group for COVID-19, and a priority for vaccination. Routine antenatal care (ANC) provides an opportunity to track trends and factors associated with vaccine uptake. We sought to evaluate COVID-19 vaccine uptake among pregnant women attending ANC and assess the factors associated with vaccine in Zambia. We conducted a repeated cross-sectional study in 39 public health facilities in four districts in Zambia from September 2021 to September 2022. Pregnant women who were aged 15-49 years were enrolled during their first ANC visit. Every month, ~20 women per facility were interviewed during individual HIV counseling and testing. We estimated vaccine uptake as the proportion of eligible participants who self-reported having received the COVID-19 vaccine. A total of 9,203 pregnant women were screened, of which 9,111 (99%) were eligible and had vaccination status. Of the 9,111 included in the analysis, 1,818 (20%) had received the COVID-19 vaccine during the study period, with a trend of increasing coverage with time (0.5% in September 2020, 27% in September 2022). Conversely, 3,789 (42%) reported not being offered a COVID-19 vaccine. We found that women aged 40-49 years, had no education or attained some primary school education, were not employed, and had prior COVID-19 infection were significantly associated with vaccine uptake. COVID-19 vaccine uptake among pregnant women was lower than estimates from the general population (27% across the four districts in September 2022), pointing to missed opportunities to protect this high-risk group. ANC visits were a viable point for conducting COVID-19 surveillance. Incorporating the vaccine as part of the routine ANC package might increase coverage in this group. |
Malaria community case management usage and quality of malaria care in a moderate Plasmodium falciparum burden region of Chadiza District, Zambia
Wallender E , Kabamba B , Rutagwera MI , Kangale C , Miller JM , Porter T , Musunse M , Gallalee S , Bennett A , Psychas P , Gutman JR , Hamainza B , Thwing J . Malar J 2024 23 (1) 226 BACKGROUND: Malaria community case management (CCM) can improve timely access to healthcare, and CCM programmes in sub-Saharan Africa are expanding from serving children under 5 years (CU5) only to all ages. This report characterizes malaria case management in the setting of an age-expanded CCM programme in Chadiza District, Zambia. METHODS: Thirty-three households in each of 73 eligible communities were randomly selected to participate in a household survey preceding a trial of proactive CCM (NCT04839900). All household members were asked about fever in the prior two weeks and received a malaria rapid diagnostic test (RDT); those reporting fever were asked about healthcare received. Weighted population estimates were calculated and mixed effects regression was used to assess factors associated with malaria care seeking. RESULTS: Among 11,030 (98.6%) participants with RDT results (2,357 households), parasite prevalence was 19.1% by RDT; school-aged children (SAC, 5-14 years) had the highest prevalence (28.8%). Prior fever was reported by 12.4% of CU5, 7.5% of SAC, and 7.2% of individuals ≥ 15 years. Among those with prior fever, 34.0% of CU5, 56.0% of SAC, and 22.6% of individuals ≥ 15 years had a positive survey RDT and 73.7% of CU5, 66.5% of SAC, and 56.3% of individuals ≥ 15 years reported seeking treatment; 76.7% across all ages visited a CHW as part of care. Nearly 90% (87.8%) of people who visited a CHW reported a blood test compared with 73.5% seen only at a health facility and/or pharmacy (p < 0.001). Reported malaria treatment was similar by provider, and 85.9% of those with a reported positive malaria test reported getting malaria treatment; 66.9% of the subset with prior fever and a positive survey RDT reported malaria treatment. Age under 5 years, monthly or more frequent CHW home visits, and greater wealth were associated with increased odds of receiving healthcare. CONCLUSIONS: Chadiza District had high CHW coverage among individuals who sought care for fever. Further interventions are needed to increase the proportion of febrile individuals who receive healthcare. Strategies to decrease barriers to healthcare, such as CHW home visits, particularly targeting those of all ages in lower wealth strata, could maximize the benefits of CHW programmes. |
WHO antenatal care policy and prevention of malaria in pregnancy in sub-Saharan Africa
Olapeju B , Bride M , Gutman JR , Wolf K , Wabwire S , Atobrah D , Babanawo F , Akrofi OO , Atta-Obeng C , Soro BK , Touré F , Shekarau E , Hendrickson ZM . Malar J 2024 23 (1) 218 BACKGROUND: The WHO 2016 antenatal care (ANC) policy recommends at least eight antenatal contacts during pregnancy. This study assessed ANC8 uptake following policy implementation and explored the relationship between ANC attendance and intermittent preventive treatment in pregnancy (IPTp) coverage in sub-Saharan Africa following the rollout of the World Health Organization (WHO) 2016 ANC policy, specifically, to assess differences in IPTp uptake between women attending eight versus four ANC contacts. METHODS: A secondary analysis of data from 20 sub-Saharan African countries with available Demographic Health and Malaria Indicator surveys from 2018 to 2023 was performed. The key variables were the number of ANC contacts and IPTp doses received during a participant's last completed pregnancy in the past two years. Pooled crude and multivariable logistic regression models were used to explore factors associated with attendance of at least four or eight ANC contacts as well as receipt of at least three doses of IPTp during pregnancy. RESULTS: Overall, only a small proportion of women (median = 3.9%) completed eight or more ANC contacts (ANC8 +). Factors significantly associated with increased odds of ANC8 + included early ANC attendance (AOR: 4.61: 95% CI 4.30-4.95), literacy (AOR: 1.20; 95% CI 1.11-1.29), and higher wealth quintile (AOR: 3.03; 95% CI 2.67-3.44). The pooled estimate across all countries showed a very slight increase in the odds of IPTp3 + among women with eight (AOR: 1.06; 95% CI 1.00-1.12) compared to those with four contacts. In all but two countries, having eight instead of four ANC contacts did not confer significantly greater odds of receiving three or more doses of IPTp (IPTp3 +), except in Ghana (AOR: 1.67; 95% CI 1.38-2.04) and Liberia (AOR: 1.43; 95% CI 1.18-1.72). CONCLUSION: Eight years after the WHO ANC policy recommendation, all countries still had sub-optimal ANC8 + coverage rates. This paper is a call to action to actualize the vision of the WHO and the global malaria community of a malaria free world. Policies to improve ANC and IPTp coverage should be operationalized with clear actionable guidance and local ownership. Study findings can be used to inform multi-level policy, programmatic, and research recommendations to optimize ANC attendance and malaria in pregnancy prevention, thus improving maternal and child health outcomes, including the reduction of malaria in pregnancy. |
Modeling the impact of proactive community case management on reducing confirmed malaria cases in Sub-Saharan African countries
Wang Y , Wang X , Gurbaxani B , Gutman JR , Keskinocak P , Smalley HK , Thwing J . Am J Trop Med Hyg 2024 Malaria continues to be a major source of morbidity and mortality in sub-Saharan Africa. Timely, accurate, and effective case management is critical to malaria control. Proactive community case management (ProCCM) is a new strategy in which a community health worker "sweeps" a village, visiting households at defined intervals to proactively provide diagnostic testing and treatment if indicated. Pilot experiments have shown the potential of ProCCM for controlling malaria transmission; identifying the best strategy for administering ProCCM in terms of interval timings and number of sweeps could lead to further reductions in malaria infections. We developed an agent-based simulation to model malaria transmission and the impact of various ProCCM strategies. The model was validated using symptomatic prevalence data from a ProCCM pilot study in Senegal. Various ProCCM strategies were tested to evaluate the potential for reducing parasitologically confirmed symptomatic malaria cases in the Senegal setting. We found that weekly ProCCM sweeps during a 21-week transmission season could reduce cases by 36.3% per year compared with no sweeps. Alternatively, two initial fortnightly sweeps, seven weekly sweeps, and finally four fortnightly sweeps (13 sweeps total) could reduce confirmed malaria cases by 30.5% per year while reducing the number of diagnostic tests and corresponding costs by about 33%. Under a highly seasonal transmission setting, starting the sweeps early with longer duration and higher frequency would increase the impact of ProCCM, though with diminishing returns. The model is flexible and allows decision-makers to evaluate implementation strategies incorporating sweep frequency, time of year, and available budget. |
Antenatal care services in Benin and Tanzania 2021/2022: an equity analysis study
Ochieng W , Munsey A , Kinyina A , Assenga M , Onikpo F , Binazon A , Adeyemi M , Alao M , Aron S , Nhiga S , Niemczura J , Buekens J , Kitojo C , Reaves E , Husseini AS , Drake M , Wolf K , Suhowatsky S , Hounto A , Lemwayi R , Gutman J . BMJ Public Health 2024 2 (1) INTRODUCTION: Antenatal care (ANC) interventions improve maternal and neonatal outcomes. However, access to ANC may be inequitable due to sociocultural, monetary and time factors. Examining drivers of ANC disparities may identify those amenable to policy change. METHODS: We conducted an ANC services equity analysis in selected public facilities in Geita, Tanzania, where most services are free to the end-user, and Atlantique, Benin, where every visit incurs user fees. Data on total ANC contacts, quality of care (QoC) indicators and wait times were collected from representative household surveys in the catchment of 40 clinics per country and were analysed by education and wealth. We used indices of inequality, concentration indices and Oaxaca-Blinder decompositions to determine the distribution, direction and magnitude of inequalities and their contributing factors. We assessed out-of-pocket expenses and the benefit incidence of government funding. RESULTS: ANC clients in both countries received less than the recommended minimum ANC contacts: 3.41 (95% CI 3.36 to 3.41) in Atlantique and 3.33 (95% CI 3.27 to 3.39) in Geita. Wealthier individuals had more ANC contacts than poorer ones at every education level in both countries; the wealthiest and most educated had two visits more than the poorest, least educated. In Atlantique, ANC attendees receive similar QoC regardless of socioeconomic status. In Geita, there are wide disparities in QoC received by education or wealth. In Atlantique, out-of-pocket expenses for the lowest wealth quintile are 2.7% of annual income compared with 0.8% for the highest, with user fees being the primary expense. In Geita, the values are 3.1% and 0.5%, respectively; transportation is the main expense. CONCLUSIONS: Inequalities in total ANC visits favouring wealthier, more educated individuals were apparent in both countries. In Atlantique, reduction of user-fees could improve ANC access. In Geita, training and equipping healthcare staff could improve QoC. Community health services could mitigate access barriers. |
Expanding community case management of malaria to all ages can improve universal access to malaria diagnosis and treatment: results from a cluster randomized trial in Madagascar
Garchitorena A , Harimanana A , Irinantenaina J , Razanadranaivo HL , Rasoanaivo TF , Sayre D , Gutman JR , Mangahasimbola RT , Ravaoarimanga M , Raobela O , Razafimaharo LY , Ralemary N , Andrianasolomanana M , Pontarollo J , Mukerabirori A , Ochieng W , Dentinger CM , Kapesa L , Steinhardt LC . BMC Med 2024 22 (1) 231 BACKGROUND: Global progress on malaria control has stalled recently, partly due to challenges in universal access to malaria diagnosis and treatment. Community health workers (CHWs) can play a key role in improving access to malaria care for children under 5 years (CU5), but national policies rarely permit them to treat older individuals. We conducted a two-arm cluster randomized trial in rural Madagascar to assess the impact of expanding malaria community case management (mCCM) to all ages on health care access and use. METHODS: Thirty health centers and their associated CHWs in Farafangana District were randomized 1:1 to mCCM for all ages (intervention) or mCCM for CU5 only (control). Both arms were supported with CHW trainings on malaria case management, community sensitization on free malaria care, monthly supervision of CHWs, and reinforcement of the malaria supply chain. Cross-sectional household surveys in approximately 1600 households were conducted at baseline (Nov-Dec 2019) and endline (Nov-Dec 2021). Monthly data were collected from health center and CHW registers for 36 months (2019-2021). Intervention impact was assessed via difference-in-differences analyses for survey data and interrupted time-series analyses for health system data. RESULTS: Rates of care-seeking for fever and malaria diagnosis nearly tripled in both arms (from less than 25% to over 60%), driven mostly by increases in CHW care. Age-expanded mCCM yielded additional improvements for individuals over 5 years in the intervention arm (rate ratio for RDTs done in 6-13-year-olds, RR(RDT6-13 years) = 1.65; 95% CIs 1.45-1.87), but increases were significant only in health system data analyses. Age-expanded mCCM was associated with larger increases for populations living further from health centers (RR(RDT6-13 years) = 1.21 per km; 95% CIs 1.19-1.23). CONCLUSIONS: Expanding mCCM to all ages can improve universal access to malaria diagnosis and treatment. In addition, strengthening supply chain systems can achieve significant improvements even in the absence of age-expanded mCCM. TRIAL REGISTRATION: The trial was registered at the Pan-African Clinical Trials Registry (#PACTR202001907367187). |
Impact of sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine as intermittent preventive treatment in pregnancy on stool antimicrobial resistance gene abundance
Opoku KB , Tompkins K , Waltmann A , Ciccone EJ , Bartlelt L , Andermann T , Chinkhumba J , Mathanga DP , Gutman JR , Juliano JJ . Am J Trop Med Hyg 2024 ![]() Increasing antimicrobial resistance (AMR) is a global public health emergency. Although chemoprevention has improved malaria-related pregnancy outcomes, the downstream effects on AMR have not been characterized. We compared the abundance of 10 AMR genes in stool samples from pregnant women receiving sulfadoxine-pyrimethamine (SP) as intermittent preventive treatment against malaria in pregnancy (IPTp) to that in samples from women receiving dihydroartemisinin-piperaquine (DP) for IPTp. All participants had at least one AMR gene at baseline. Mean quantities of the antifolate gene dfrA17 were increased after two or more doses of SP (mean difference = 1.6, 95% CI: 0.4-2.7, P = 0.008). Antimicrobial resistance gene abundance tended to increase from baseline in SP recipients compared with a downward trend in the DP group. Overall, IPTp-SP had minimal effects on the abundance of antifolate resistance genes (except for dfrA17), potentially owing to a high starting prevalence. However, the trend toward increasing AMR in SP recipients warrants further studies. |
Trends in SARS-CoV-2 seroprevalence among pregnant women attending first antenatal care visits in Zambia: A repeated cross-sectional survey, 2021-2022
Heilmann E , Tembo T , Fwoloshi S , Kabamba B , Chilambe F , Kalenga K , Siwingwa M , Mulube C , Seffren V , Bolton-Moore C , Simwanza J , Yingst S , Yadav R , Rogier E , Auld AF , Agolory S , Kapina M , Gutman JR , Savory T , Kangale C , Mulenga LB , Sikazwe I , Hines JZ . PLOS Glob Public Health 2024 4 (4) e0003073 SARS-CoV-2 serosurveys help estimate the extent of transmission and guide the allocation of COVID-19 vaccines. We measured SARS-CoV-2 seroprevalence among women attending ANC clinics to assess exposure trends over time in Zambia. We conducted repeated cross-sectional SARS-CoV-2 seroprevalence surveys among pregnant women aged 15-49 years attending their first ANC visits in four districts of Zambia (two urban and two rural) during September 2021-September 2022. Serologic testing was done using a multiplex bead assay which detects IgG antibodies to the nucleocapsid protein and the spike protein receptor-binding domain (RBD). We calculated monthly SARS-CoV-2 seroprevalence by district. We also categorized seropositive results as infection alone, infection and vaccination, or vaccination alone based on anti-RBD and anti-nucleocapsid test results and self-reported COVID-19 vaccination status (vaccinated was having received ≥1 dose). Among 8,304 participants, 5,296 (63.8%) were cumulatively seropositive for SARS-CoV-2 antibodies from September 2021 through September 2022. SARS-CoV-2 seroprevalence primarily increased from September 2021 to September 2022 in three districts (Lusaka: 61.8-100.0%, Chongwe: 39.6-94.7%, Chipata: 56.5-95.0%), but in Chadiza, seroprevalence increased from 27.8% in September 2021 to 77.2% in April 2022 before gradually dropping to 56.6% in July 2022. Among 5,906 participants with a valid COVID-19 vaccination status, infection alone accounted for antibody responses in 77.7% (4,590) of participants. Most women attending ANC had evidence of prior SARS-CoV-2 infection and most SARS-CoV-2 seropositivity was infection-induced. Capturing COVID-19 vaccination status and using a multiplex bead assay with anti-nucleocapsid and anti-RBD targets facilitated distinguishing infection-induced versus vaccine-induced antibody responses during a period of increasing COVID-19 vaccine coverage in Zambia. Declining seroprevalence in Chadiza may indicate waning antibodies and a need for booster vaccines. ANC clinics have a potential role in ongoing SARS-CoV-2 serosurveillance and can continue to provide insights into SARS-CoV-2 antibody dynamics to inform near real-time public health responses. |
SARS-CoV-2 seroprevalence and vaccine uptake among pregnant women at first antenatal care visits in Malawi
Tenthani L , Seffren V , Kabaghe AN , Ogollah F , Soko M , Yadav R , Kayigamba F , Payne D , Wadonda-Kabondo N , Kampira E , Volkmann T , Sugandhi NS , Seydel K , Rogier E , Thwing JI , Gutman JR . Am J Trop Med Hyg 2024 Many SARS-CoV-2 infections are asymptomatic, thus reported cases underestimate actual cases. To improve estimates, we conducted surveillance for SARS-CoV-2 seroprevalence among pregnant women attending their first antenatal care visit (ANC1) from June 2021 through May 2022. We administered a questionnaire to collect demographic, risk factors, and COVID-19 vaccine status information and tested dried blood spots for SARS-CoV-2 antibodies. Although <1% of ANC1 participants reported having had COVID-19, monthly SARS-CoV-2 seroprevalence increased from 15.4% (95% CI: 10.5-21.5) in June 2021 to 65.5% (95% CI: 55.5-73.7) in May 2022. Although COVID-19 vaccination was available in March 2021, uptake remained low, reaching a maximum of 9.5% (95% CI: 5.7-14.8) in May 2022. Results of ANC1 serosurveillance provided prevalence estimates helpful in understanding this population case burden that was available through self-report and national case reports. To improve vaccine uptake, efforts to address fears and misconceptions regarding COVID-19 vaccines are needed. |
Prevalence of non-falciparum malaria infections among asymptomatic individuals in four regions of Mainland Tanzania
Popkin-Hall ZR , Seth MD , Madebe RA , Budodo R , Bakari C , Francis F , Pereus D , Giesbrecht DJ , Mandara CI , Mbwambo D , Aaron S , Lusasi A , Lazaro S , Bailey JA , Juliano JJ , Gutman JR , Ishengoma DS . Parasit Vectors 2024 17 (1) 153 BACKGROUND: Recent studies point to the need to incorporate the detection of non-falciparum species into malaria surveillance activities in sub-Saharan Africa, where 95% of the world's malaria cases occur. Although malaria caused by infection with Plasmodium falciparum is typically more severe than malaria caused by the non-falciparum Plasmodium species P. malariae, P. ovale spp. and P. vivax, the latter may be more challenging to diagnose, treat, control and ultimately eliminate. The prevalence of non-falciparum species throughout sub-Saharan Africa is poorly defined. Tanzania has geographical heterogeneity in transmission levels but an overall high malaria burden. METHODS: To estimate the prevalence of malaria species in Mainland Tanzania, we randomly selected 1428 samples from 6005 asymptomatic isolates collected in previous cross-sectional community surveys across four regions and analyzed these by quantitative PCR to detect and identify the Plasmodium species. RESULTS: Plasmodium falciparum was the most prevalent species in all samples, with P. malariae and P. ovale spp. detected at a lower prevalence (< 5%) in all four regions; P. vivax was not detected in any sample. CONCLUSIONS: The results of this study indicate that malaria elimination efforts in Tanzania will need to account for and enhance surveillance of these non-falciparum species. |
Mass drug administration: Contextual factor considerations
Schneider ZD , Busbee AL , Boily MC , Shah MP , Hwang J , Lindblade KA , Gutman JR . Am J Trop Med Hyg 2024 In designing mass drug administration (MDA) campaigns, it is imperative to consider contextual factors that affect uptake of the intervention, including acceptability, cost, feasibility, and health system considerations, to ensure optimal coverage. We reviewed the literature on contextual factors influencing MDA delivery to provide programs with information to design a successful campaign. From 1,044 articles screened, 37 included contextual factors relevant to participants' values and preferences, drivers of MDA acceptability, health equity concerns, financial and economic aspects, and feasibility barriers; 13 included relevant modeling data. Key findings were abstracted by two reviewers and summarized. No studies directly assessed values or direct health equity concerns with respect to MDA, which represents an evidence gap as unequal distributions of effects and factors that impact participant acceptability and program feasibility must be considered to ensure equitable access. Participant acceptability was the most widely surveyed factor, appearing in 28 of 37 studies; perceived adverse events were a frequently noted cause of nonparticipation, mentioned in 15 studies. Feasibility considerations included when, where, and how drugs will be delivered and how to address pregnant women, as these can all have substantial implications for participation. Mass drug administration costs (∼$1.04 to $19.40 per person per round) are driven primarily by drug prices, but the delivery mechanism can have varying costs as well, and integration with other interventions may provide cost savings. Both programmatic goals and sociopolitical and economic contexts must be carefully considered before embarking on an MDA program to ensure programmatic success. |
Malaria species prevalence among asymptomatic individuals in four regions of Mainland Tanzania
Popkin Hall ZR , Seth MD , Madebe RA , Budodo R , Bakari C , Francis F , Pereus D , Giesbrecht DJ , Mandara CI , Mbwambo D , Aaron S , Lusasi A , Lazaro S , Bailey JA , Juliano JJ , Gutman JR , Ishengoma DS . medRxiv 2023 Recent studies point to the need to incorporate non-falciparum species detection into malaria surveillance activities in sub-Saharan Africa, where 95% of malaria cases occur. Although Plasmodium falciparum infection is typically more severe, diagnosis, treatment, and control for P. malariae, P. ovale spp., and P. vivax may be more challenging. The prevalence of these species throughout sub-Saharan Africa is poorly defined. Tanzania has geographically heterogeneous transmission levels but an overall high malaria burden. In order to estimate the prevalence of malaria species in Mainland Tanzania, 1,428 samples were randomly selected from 6,005 asymptomatic isolates collected in cross-sectional community surveys across four regions and analyzed via qPCR to detect each Plasmodium species. P. falciparum was most prevalent, with P. malariae and P. ovale spp. detected at lower prevalence (<5%) in all four regions. P. vivax was not detected. Malaria elimination efforts in Tanzania will need to account for these non-falciparum species. |
Iatrogenic and demographic determinants of the national plural birth increase
Adashi EY , Penzias AS , Gruppuso PA , Kulkarni AD , Zhang Y , Kissin DM , Gutman R . Fertil Steril 2024 ![]() OBJECTIVE: To study the contribution of ovulation induction and ovarian stimulation, in vitro fertilization (IVF) and unassisted conception to the increase in national plural births in the U.S., a significant contributor to adverse maternal and infant health outcomes. DESIGN: National and IVF-assisted plural birth data were derived from the Centers for Disease Control and Prevention's National Vital Statistics System (1967-2021, after introduction of Clomiphene Citrate in the U.S.) and the National Assisted Reproductive Technology Surveillance System (1997-2021), respectively. MAIN OUTCOME MEASURES: In addition to IVF-assisted plural births, the contributions of unassisted conception to plural births among women aged <35 and ≥35 years were estimated using plural birth rates from 1949-1966, and a Bayesian logistic model with race and age as independent variables. The contribution of ovulation induction and ovarian stimulation was estimated as the difference between national plural births and IVF-assisted and unassisted counterparts. RESULTS: From 1967-2021, the national twin birth rate increased 1.7-fold to a 2014 high (33.9/1000 live births), then declined to 31.2/1000 live births; the triplet and higher-order birth rate increased 6.7-fold to a 1998 high (1.9/1000 live births), then declined to 0.8/1000 live births. In 2021, the contribution of unassisted conception among women <35 to the national plural births was 56.1%, followed by ovulation induction and ovarian stimulation (19.5%), unassisted conception among women ≥35 (16.8%) and IVF (7.6%). During 2009-2021, the contribution of ovulation induction and ovarian stimulation has remained stable, the contribution of unassisted conception among women <35 and women ≥35 has increased, and the contribution of IVF has decreased. CONCLUSION: Ovulation induction and ovarian stimulation are leading iatrogenic contributors to plural births. They are, therefore, targets for intervention to reduce the adverse maternal and infant health outcomes associated with plural births. Maternal age ≥35 is a significant contributor to the national plural birth increase. |
Chemoprevention for malaria with monthly intermittent preventive treatment with dihydroartemisinin-piperaquine in pregnant women living with HIV on daily co-trimoxazole in Kenya and Malawi: a randomised, double-blind, placebo-controlled trial
Barsosio HC , Madanitsa M , Ondieki ED , Dodd J , Onyango ED , Otieno K , Wang D , Hill J , Mwapasa V , Phiri KS , Maleta K , Taegtmeyer M , Kariuki S , Schmiegelow C , Gutman JR , Ter Kuile FO . Lancet 2024 403 (10424) 365-378 BACKGROUND: The efficacy of daily co-trimoxazole, an antifolate used for malaria chemoprevention in pregnant women living with HIV, is threatened by cross-resistance of Plasmodium falciparum to the antifolate sulfadoxine-pyrimethamine. We assessed whether addition of monthly dihydroartemisinin-piperaquine to daily co-trimoxazole is more effective at preventing malaria infection than monthly placebo plus daily co-trimoxazole in pregnant women living with HIV. METHODS: We did an individually randomised, two-arm, placebo-controlled trial in areas with high-grade sulfadoxine-pyrimethamine resistance in Kenya and Malawi. Pregnant women living with HIV on dolutegravir-based combination antiretroviral therapy (cART) who had singleton pregnancies between 16 weeks' and 28 weeks' gestation were randomly assigned (1:1) by computer-generated block randomisation, stratified by site and HIV status (known positive vs newly diagnosed), to daily co-trimoxazole plus monthly dihydroartemisinin-piperaquine (three tablets of 40 mg dihydroartemisinin and 320 mg piperaquine given daily for 3 days) or daily co-trimoxazole plus monthly placebo. Daily co-trimoxazole consisted of one tablet of 160 mg sulfamethoxazole and 800 mg trimethoprim. The primary endpoint was the incidence of Plasmodium infection detected in the peripheral (maternal) or placental (maternal) blood or tissue by PCR, microscopy, rapid diagnostic test, or placental histology (active infection) from 2 weeks after the first dose of dihydroartemisinin-piperaquine or placebo to delivery. Log-binomial regression was used for binary outcomes, and Poisson regression for count outcomes. The primary analysis was by modified intention to treat, consisting of all randomised eligible participants with primary endpoint data. The safety analysis included all women who received at least one dose of study drug. All investigators, laboratory staff, data analysts, and participants were masked to treatment assignment. This trial is registered with ClinicalTrials.gov, NCT04158713. FINDINGS: From Nov 11, 2019, to Aug 3, 2021, 904 women were enrolled and randomly assigned to co-trimoxazole plus dihydroartemisinin-piperaquine (n=448) or co-trimoxazole plus placebo (n=456), of whom 895 (99%) contributed to the primary analysis (co-trimoxazole plus dihydroartemisinin-piperaquine, n=443; co-trimoxazole plus placebo, n=452). The cumulative risk of any malaria infection during pregnancy or delivery was lower in the co-trimoxazole plus dihydroartemisinin-piperaquine group than in the co-trimoxazole plus placebo group (31 [7%] of 443 women vs 70 [15%] of 452 women, risk ratio 0·45, 95% CI 0·30-0·67; p=0·0001). The incidence of any malaria infection during pregnancy or delivery was 25·4 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 77·3 per 100 person-years in the co-trimoxazole plus placebo group (incidence rate ratio 0·32, 95% CI 0·22-0·47, p<0·0001). The number needed to treat to avert one malaria infection per pregnancy was 7 (95% CI 5-10). The incidence of serious adverse events was similar between groups in mothers (17·7 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group [23 events] vs 17·8 per 100 person-years in the co-trimoxazole group [25 events]) and infants (45·4 per 100 person-years [23 events] vs 40·2 per 100 person-years [21 events]). Nausea within the first 4 days after the start of treatment was reported by 29 (7%) of 446 women in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 12 (3%) of 445 women in the co-trimoxazole plus placebo group. The risk of adverse pregnancy outcomes did not differ between groups. INTERPRETATION: Addition of monthly intermittent preventive treatment with dihydroartemisinin-piperaquine to the standard of care with daily unsupervised co-trimoxazole in areas of high antifolate resistance substantially improves malaria chemoprevention in pregnant women living with HIV on dolutegravir-based cART and should be considered for policy. FUNDING: European and Developing Countries Clinical Trials Partnership 2; UK Joint Global Health Trials Scheme (UK Foreign, Commonwealth and Development Office; Medical Research Council; National Institute for Health Research; Wellcome); and Swedish International Development Cooperation Agency. |
Multiple imputation of missing race/ethnicity information in the National Assisted Reproductive Technology Surveillance System
Zhang Y , Kissin DM , Liao KJ , DeSantis CE , Yartel AK , Gutman R . J Womens Health (Larchmt) 2023 Background: Missing race/ethnicity data are common in many surveillance systems and registries, which may limit complete and accurate assessments of racial and ethnic disparities. Centers for Disease Control and Prevention's National Assisted Reproductive Technology (ART) Surveillance System (NASS) has a congressional mandate to collect data on all ART cycles performed by fertility clinics in the United States and provides valuable information on ART utilization and treatment outcomes. However, race/ethnicity data are missing for many ART cycles in NASS. Materials and Methods: We multiply imputed missing race/ethnicity data using variables from NASS and additional zip code-level race/ethnicity information in U.S. Census data. To evaluate imputed data quality, we generated training data by imposing missing values on known race/ethnicity under missing at random assumption, imputed, and examined the relationship between race/ethnicity and the rate of stillbirth per pregnancy. Results: The distribution of imputed race/ethnicity was comparable to the reported one with the largest difference of 0.53% for non-Hispanic Asian. Our imputation procedure was well calibrated and correctly identified that 89.91% (standard error = 0.18) of known race/ethnicity values on average in training data. Compared to complete-case analysis, using multiply imputed data reduced bias of parameter estimates (the range of bias for stillbirth per pregnancy across race/ethnicity groups is 0.02%-0.18% for imputed data analysis, versus 0.04%-0.66% for complete-case analysis) and yielded narrower confidence intervals. Conclusions: Our results underscore the importance of collecting complete race/ethnicity information for ART surveillance. However, when the missingness exists, multiply imputed race/ethnicity can improve the accuracy and precision of health outcomes estimated across racial/ethnic groups. |
Development of systematic reviews to inform WHO's recommendations for elimination and prevention of re-establishment of malaria: Methodology
Tusell M , Steinhardt LC , Gutman J , Schneider ZD , Bhamani B , Shah MP , Martí Coma-Cros E , Gimnig JE , Allen KC , Akl EA , Lindblade KA . Am J Trop Med Hyg 2023 The basis for an evidence-based recommendation is a well-conducted systematic review that synthesizes the primary literature relevant to the policy or program question of interest. In 2020, the WHO commissioned 10 systematic reviews of potential interventions in elimination or post-elimination settings to summarize their impact on malaria transmission. This paper describes the general methods used to conduct this series of systematic reviews and notes where individual reviews diverged from the common methodology. The paper also presents lessons learned from conducting the systematic reviews to make similar future efforts more efficient, standardized, and streamlined. |
Mass drug administration to reduce malaria transmission: A systematic review and meta-analysis
Schneider ZD , Shah MP , Boily MC , Busbee AL , Hwang J , Lindblade KA , Gutman JR . Am J Trop Med Hyg 2023 Malaria remains a significant cause of morbidity and mortality, even in low-transmission settings. With the advent of longer acting, more effective, and well-tolerated antimalarials, there is renewed interest in the efficacy of mass drug administration (MDA) to accelerate to elimination. We conducted a systematic review and meta-analysis to assess the efficacy of MDA to reduce the incidence and prevalence of Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) infection. From 1,044 articles screened, 14 articles, including 10 randomized controlled trials (RCTs), were identified. Five included data on Pf only; five included Pf and Pv. Two of the Pf studies were conducted in areas of high-moderate transmission, the remainder were in areas of low-very low transmission. In higher transmission areas, MDA reduced incidence of Pf parasitemia (rate ratio = 0.61, 95% CI: 0.40-0.92; moderate certainty) 1 to 3 months after drug administration; no significant effect of MDA on Pf parasitemia prevalence was detected 1 to 3 months post-MDA (risk ratio [RR] = 1.76, 95% CI: 0.58-5.36; low certainty). In lower transmission settings, both incidence and prevalence of Pf parasitemia were reduced 1 to 3 months post-MDA (rate ratio = 0.37, 95% CI: 0.21-0.66; RR = 0.25, 95% CI: 0.15-0.41, respectively). Pv prevalence was reduced 1 to 3 months post-MDA (RR = 0.15, 95% CI: 0.10-0.24); there were no RCTs providing data on incidence of Pv. There was no significant effect of MDA at later time points. MDA may have short-term benefits; however, there was no evidence for longer term impact, although none of the trials assessed prolonged interventions. |
Use of supervision data to improve quality of care for malaria in pregnancy: Experience in six African countries
Wolf K , Mostel J , Oseni L , Gomez P , Kibuka T , Emerson C , Gutman JR , Malpass A , Youll S , Mukamba JY , Tchinda E , Achu D , Tjek P , Assa JL , Silue M , Tanoh MA , Kokrasset-Yah C , Babanawo F , Asiedu A , Komey M , Boateng P , Mabiria M , Ngindu A , Njiru P , Omar AH , Sidibe FA , Diallo C , Kamate B , Kone A , Elisha S , Maiga AD , Mayaki AI , Tidjani Issa Gana F , Tetteh G . Am J Trop Med Hyg 2023 Malaria in pregnancy (MiP) intervention coverage, especially intermittent preventive treatment in pregnancy (IPTp), lags behind other global malaria indicators. In 2020, across Africa, only 32% of eligible pregnant women received at least three IPTp doses, despite high antenatal care attendance. We conducted a secondary analysis of data collected during outreach, training, and supportive supervision visits from 2019 to 2020 to assess quality of care and explore factors contributing to providers' competence in providing IPTp, insecticide-treated nets, malaria case management, and respectful maternity care. Data were collected during observations of provider-patient interactions in six countries (Cameroon, Cote d'Ivoire, Ghana, Kenya, Mali, and Niger). Competency scores (i.e., composite scores of supervisory checklist observations) were calculated across three domains: MiP prevention, MiP treatment, and respectful maternity care. Scores are used to understand drivers of competency, rather than to assess individual health worker performance. Country-specific multilinear regressions were used to assess how competency score was influenced by commodity availability, training, provider gender and cadre, job aid availability, and facility type. Average competency scores varied across countries: prevention (44-90%), treatment (78-90%), and respectful maternity care (53-93%). The relative association of each factor with competency score varied. Commodity availability, training, and access to job aids correlated positively with competency in multiple countries. To improve MiP service quality, equitable access to training opportunities for different cadres, targeted training, and access to job aids and guidelines should be available for providers. Collection and analysis of routine supervision data can support tailored actions to improve quality MiP services. |
Contextual factors to improve implementation of malaria chemoprevention in children: A systematic review
Gatiba P , Laury J , Steinhardt L , Hwang J , Thwing JI , Zulliger R , Emerson C , Gutman JR . Am J Trop Med Hyg 2023 110 (1) 69-78 Malaria remains a leading cause of childhood morbidity and mortality in sub-Saharan Africa, particularly among children under 5 years of age. To help address this challenge, the WHO recommends chemoprevention for certain populations. For children and infants, the WHO recommends seasonal malaria chemoprevention (SMC), perennial malaria chemoprevention (PMC; formerly intermittent preventive treatment in infants [IPTi]), and, more recently, intermittent preventive treatment in school children (IPTsc). This review describes the contextual factors, including feasibility, acceptability, health equity, financial considerations, and values and preferences, that impact implementation of these strategies. A systematic search was conducted on July 5, 2022, and repeated April 13, 2023, to identify relevant literature. Two reviewers independently screened titles for eligibility, extracted data from eligible articles, and identified and summarized themes. Of 6,295 unique titles identified, 65 were included. The most frequently evaluated strategy was SMC (n = 40), followed by IPTi (n = 18) and then IPTsc (n = 6). Overall, these strategies were highly acceptable, although with IPTsc, there were community concerns with providing drugs to girls of reproductive age and the use of nonmedical staff for drug distribution. For SMC, door-to-door delivery resulted in higher coverage, improved caregiver acceptance, and reduced cost. Lower adherence was noted when caregivers were charged with giving doses 2 and 3 unsupervised. For SMC and IPTi, travel distances and inclement weather limited accessibility. Sensitization and caregiver education efforts, retention of high-quality drug distributors, and improved transportation were key to improving coverage. Additional research is needed to understand the role of community values and preferences in chemoprevention implementation. |
Systematic review and meta-analysis of seasonal malaria chemoprevention
Thwing J , Williamson J , Cavros I , Gutman JR . Am J Trop Med Hyg 2023 110 (1) 20-31 Seasonal malaria chemoprevention (SMC) for children under 5 years of age for up to four monthly cycles during malaria transmission season was recommended by the WHO in 2012 and has been implemented in 13 countries in the Sahel, reaching more than 30 million children annually. Malaria control programs implementing SMC have asked the WHO to consider expanding the age range or number of monthly cycles. We conducted a systematic review and meta-analysis of SMC among children up to 15 years of age and up to six monthly cycles. Twelve randomized studies were included, with outcomes stratified by age (< 5/≥ 5 years), by three or four versus five or six cycles, and by drug where possible. Drug regimens included sulfadoxine-pyrimethamine + amodiaquine, amodiaquine-artesunate, and sulfadoxine-pyrimethamine + artesunate. Included studies were all conducted in Sahelian countries in which high-grade resistance to sulfadoxine-pyrimethamine was rare and in zones with parasite prevalence ranging from 1% to 79%. Seasonal malaria chemoprevention resulted in substantial reductions in uncomplicated malaria incidence measured during that transmission season (rate ratio: 0.27, 95% CI: 0.25-0.29 among children < 5 years; rate ratio: 0.27, 95% CI: 0.25-0.30 among children ≥ 5 years) and in the prevalence of malaria parasitemia measured within 4-6 weeks from the final SMC cycle (risk ratio: 0.38, 95% CI: 0.34-0.43 among children < 5 years; risk ratio: 0.23, 95% CI: 0.11-0.48 among children ≥ 5 years). In high-transmission zones, SMC resulted in a moderately reduced risk of any anemia (risk ratio: 0.77, 95% CI: 0.72-0.83 among children < 5 years; risk ratio: 0.70, 95% CI: 0.52-0.95 among children ≥ 5 years [one study]). Children < 10 years of age had a moderate reduction in severe malaria (risk ratio: 0.53, 95% CI: 0.37-0.76) but no evidence of a mortality reduction. The evidence suggests that in areas in which sulfadoxine-pyrimethamine and amodiaquine remained efficacious, SMC effectively reduced malaria disease burden among children both < 5 and ≥ 5 years old and that the number of cycles should be commensurate with the length of the transmission season, up to six cycles. |
Late morning biting behaviour of Anopheles funestus is a risk factor for transmission in schools in Siaya, western Kenya
Omondi S , Kosgei J , Musula G , Muchoki M , Abong'o B , Agumba S , Ogwang C , McDermott DP , Donnelly MJ , Staedke SG , Schultz J , Gutman JR , Gimnig JE , Ochomo E . Malar J 2023 22 (1) 366 BACKGROUND: Children in Kenya spend a substantial amount of time at school, including at dawn and dusk when mosquitoes are active. With changing vector behaviour towards early morning biting, it is important to determine whether there is an additional risk of transmission in schools. This study sought to understand whether late morning biting by Anopheles funestus, previously documented in households in western Kenya, was replicated in schools. METHODS: From the 4th to the 6th of August 2023, human landing collections were conducted hourly in four schools in Alego Usonga sub-County, Siaya County. The collections were conducted in and outside five classrooms in each school and ran for 17 h, starting at 18:00 until 11:00 h the next morning. RESULTS: Anopheles funestus was the predominant species collected, forming 93.2% (N = 727) of the entire collection, with peak landing between 06:00 and 07:00 h and continuing until 11:00 h. More than half of the collected An. funestus were either fed or gravid, potentially indicative of multiple bloodmeals within each gonotrophic cycle, and had a sporozoite rate of 2.05%. CONCLUSION: School children spend up to 10 h of their daytime in schools, reporting between 06:00 and 07:00 h and staying in school until as late as 17:00 h, meaning that they receive potentially infectious mosquito bites during the morning hours in these settings. There is a need to consider vector control approaches targeting schools and other peridomestic spaces in the morning hours when An. funestus is active. |
Have you heard the news? Artemether-lumefantrine is now recommended for ALL uncomplicated malaria in the United States, including in pregnancy
Castro L , Ridpath A , Mace K , Gutman JR . Clin Infect Dis 2023 Malaria is a serious and potentially fatal disease transmitted through the bite of an infective | female anopheline mosquito; pregnant people are more susceptible to malaria infection than nonpregnant people, and are at risk of significant adverse consequences for both mother and infant.1 | | These include maternal anemia, fetal growth retardation, stillbirth, premature birth, and low | birthweight.2 | Rarely, malaria can be transmitted congenitally from mother to fetus or to the | neonate at birth. Globally, it is estimated that over 13 million pregnancies were affected by | malaria in 2021, leading to an estimated 505,000 infants born with low birth weight.3 While | malaria in pregnancy is rarely seen in the United States, it nonetheless occurs, with 19 cases | among pregnant women (both travelers and refugees/immigrants) reported in the US in 2018, | 4 27 | in 2019 (Mace, unpublished data), and 8 in 2020 (Mace, unpublished data), and needs to be | recognized and treated quickly to prevent adverse effects to the mother and infant. |
Peripheral and placental prevalence of sulfadoxine-pyrimethamine resistance markers in plasmodium falciparum among pregnant women in Southern Province, Rwanda
Alruwaili M , Uwimana A , Sethi R , Murindahabi M , Piercefield E , Umulisa N , Abram A , Eckert E , Munguti K , Mbituyumuremyi A , Gutman JR , Sullivan DJ . Am J Trop Med Hyg 2023 109 (5) 1057-1062 ![]() Intermittent preventive therapy during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended in areas of moderate to high malaria transmission intensity. As a result of the increasing prevalence of SP resistance markers, IPTp-SP was withdrawn from Rwanda in 2008. Nonetheless, more recent findings suggest that SP may improve birthweight even in the face of parasite resistance, through alternative mechanisms that are independent of antimalarial effects. The prevalence of single nucleotide polymorphisms in Plasmodium falciparum dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr) genes associated with SP resistance among 148 pregnant women from 2016 to 2018 within Rwanda's Southern Province (Huye and Kamonyi districts) was measured using a ligase detection reaction-fluorescent microsphere assay. The frequency of pfdhps K540E, A581G, and the quintuple (pfdhfr N51I + C59R + S108N/pfdhps A437G + K540E) and sextuple (pfdhfr N51I + C59R + S108N/pfdhps A437G + K540E + A581G) mutant genotypes was 90%, 38%, 75%, and 28%, respectively. No significant genotype difference was seen between the two districts, which are approximately 50 km apart. Observed agreements for matched peripheral to placental blood were reported and found to be 207 of 208 (99%) for pfdhfr and 239 of 260 (92%) for pfdhps. The peripheral blood sample did not miss any pfdhfr drug-resistant mutants or pfdhps except at the S436 loci. At this level of the sextuple mutant, the antimalarial efficacy of SP for preventing low birthweight is reduced, although overall SP still exerts a nonmalarial benefit during pregnancy. This study further reveals the need to intensify preventive measures to sustain malaria control in Rwanda to keep the overall incidence of malaria during pregnancy low. |
Perceptions and drivers of healthcare provider and drug dispenser practices for the treatment of malaria in pregnancy in the context of multiple first-line therapies in western Kenya: a qualitative study
Osoro CB , Dellicour S , Ochodo E , Young T , Ter Kuile FO , Gutman JR , Hill J . Malar J 2023 22 (1) 274 BACKGROUND: Emergence of Plasmodium falciparum resistance to artemether-lumefantrine in Africa prompted the pilot introduction of multiple first-line therapies (MFT) against malaria in Kenya, potentially exposing women-of-childbearing-age (WOCBAs) to anti-malarials with unknown safety profiles in the first trimester. This qualitative study explored knowledge and perceptions among healthcare providers providing malaria treatment to WOCBAs and pregnant women. METHODS: In-depth interviews were conducted with purposively selected public and private health facility (HF) and drug outlet (DO) providers within and outside the pilot-MFT area. County health managers were interviewed about their knowledge of the national treatment guidelines. Transcripts were coded by content analysis using the World Health Organization health system building blocks (leadership/governance, financing, health workforce, health information systems, access to medicines, and service delivery). RESULTS: Thirty providers (HF:21, DO:9) and three health managers were interviewed. Eighteen providers were from HFs in the pilot-MFT area; the remaining three and all nine DOs were outside the pilot-MFT area. The analysis revealed that providers had not been trained in malaria case management in the previous twelve months. DO providers were unfamiliar with national treatment guidelines in pregnancy and reported having no pregnancy tests. Health managers were unable to supervise DOs due to resource limitations. Providers from HFs and DOs noted poor sensitivity of malaria rapid diagnostic tests (RDTs) and hesitancy among patients who associated malaria-RDTs with HIV testing. Almost all providers reported anti-malarial stock-outs, with quinine most affected. Patient preference was a major factor in prescribing anti-malarials. Providers in HFs and DOs reported preferentially using artemether-lumefantrine in the first trimester due to the side effects and unavailability of quinine. CONCLUSION: Knowledge of malaria case management in drug outlets and health facilities remains poor. Improved regulation of DO providers is warranted. Optimizing treatment of malaria in pregnancy requires training, availability of malaria commodities, and pregnancy tests. |
Healthcare provider and drug dispenser knowledge and adherence to guidelines for the case management of malaria in pregnancy in the context of multiple first-line artemisinin-based combination therapy in western Kenya
Osoro CB , Dellicour S , Ochodo E , Young T , Ter Kuile F , Gutman JR , Hill J . Malar J 2023 22 (1) 262 BACKGROUND: Concerns about emerging resistance to artemether-lumefantrine (AL) in Africa prompted the pilot introduction of multiple first-line therapies (MFT) in Western Kenya, potentially exposing women-of-childbearing-age (WOCBA) to anti-malarials with unknown safety profiles in the first trimester. The study assessed healthcare provider knowledge and adherence to national guidelines for managing malaria in pregnancy in the context of the MFT pilot. METHODS: From March to April 2022, a cross-sectional study was conducted in 50 health facilities (HF) and 40 drug outlets (DO) using structured questionnaires to assess pregnancy detection, malaria diagnosis, and treatment choices by trimester. Differences between HF and DO providers and between MFT and non-MFT HFs were assessed using Chi-square tests. RESULTS: Of 174 providers (77% HF, 23% DO), 56% were from MFT pilot facilities. Most providers had tertiary education; 5% HF and 20% DO had only primary or secondary education. More HF than DO providers had knowledge of malaria treatment guidelines (62% vs. 40%, p = 0.023), received training in malaria in pregnancy (49% vs. 20%, p = 0.002), and reported assessing for pregnancy in WOCBA (98% vs. 78%, p < 0.001). Most providers insisted on parasitological diagnosis, with 59% HF using microscopy and 85% DO using rapid diagnostic tests. More HF than DO providers could correctly name the drugs for treating uncomplicated malaria in the first trimester (oral quinine, or AL if quinine is unavailable) (90% vs. 58%, p < 0.001), second and third trimesters (artemisinin-based combination therapy) (84% vs. 70%, p = 0.07), and for severe malaria (parenteral artesunate/artemether) (94% vs. 60%, p < 0.001). Among HF providers, those in the MFT pilot had more knowledge of malaria treatment guidelines (67% vs. 49%, p = 0.08) and had received training on treatment of malaria in pregnancy (56% vs. 32%, p = 0.03). Few providers (10% HF and 12% DO) had adequate knowledge of malaria treatment in pregnancy, defined as the correct drug and dose for uncomplicated and severe malaria in all trimesters. CONCLUSIONS: Knowledge of national malaria in pregnancy treatment guidelines among providers in Western Kenya is suboptimal. Robust training on appropriate anti-malarial and dosage is needed, particularly given the recent change in recommendation for artemether-lumefantrine use in the first trimester. Supervision of DO and HF practices is essential for correct treatment of malaria in pregnancy in the context of MFT programmes. |
Assessing the utility of pregnant women as a sentinel surveillance population for malaria in Geita, Tanzania, 2019 - 2021
Munsey A , Kinyina A , Assenga M , Almeida A , Kitojo C , Reaves E , Simeo J , Aron S , Chacky F , Nhiga SL , Drake M , Lemwayi R , Walker P , Gutman JR . Int J Infect Dis 2023 136 57-63 OBJECTIVES: Estimates of malaria burden and intervention uptake in Africa are primarily based on household surveys. However, their expense and infrequency limit their utility. We investigated whether data collected during antenatal care (ANC) can provide relevant information for decision-makers. METHODS: Malaria test positivity rates and questionnaire data from ANC attendees at 39 health facilities were compared to questionnaire data and positivity rates among children from two cross-sectional surveys in the facilities' corresponding catchment areas. RESULTS: Trends in parasitemia among ANC attendees were predictive of trends in parasitemia among children at the council level (mean absolute error 6.0%). Primigravid ANC attendees had the lowest rates of net ownership (modeled odds ratio, OR, 0.28, 95% confidence interval, CI, 0.19 - 0.40) and use (OR 0.58, 95% CI 0.42 - 0.79). ANC attendees reported higher levels of care seeking (OR 1.78, 95% CI 1.48 - 2.14), malaria testing (OR 4.16, 95% CI 3.44 - 5.04), and treatment for children with fever (OR 7.66, 95% CI 4.89 - 11.98) compared to women surveyed in households, raising concerns about social desirability bias disproportionately impacting ANC surveys. CONCLUSION: ANC surveillance is an effective strategy for tracking trends in malaria burden. More work is required to elucidate the value in administering questionnaires to ANC attendees. |
Fetal growth and birth weight are independently reduced by malaria infection and curable sexually transmitted and reproductive tract infections in Kenya, Tanzania, and Malawi: A pregnancy cohort study
Mtove G , Chico RM , Madanitsa M , Barsosio HC , Msemo OA , Saidi Q , Gore-Langton GR , Minja DTR , Mukerebe C , Gesase S , Mwapasa V , Phiri KS , Hansson H , Dodd J , Magnussen P , Kavishe RA , Mosha F , Kariuki S , Lusingu JPA , Gutman JR , Alifrangis M , Ter Kuile FO , Schmiegelow C . Int J Infect Dis 2023 135 28-40 OBJECTIVE: Malaria and sexually transmitted and reproductive tract infections (STIs/RTIs) are highly prevalent in sub-Saharan Africa and associated with poor pregnancy outcomes. We investigated the individual and combined effects of malaria and curable STIs/RTIs on fetal growth in Kenya, Tanzania, and Malawi. METHODS: This study was nested within a randomized trial comparing monthly intermittent preventive treatment for malaria in pregnancy with sulfadoxine-pyrimethamine versus dihydroartemisinin-piperaquine, alone or combined with azithromycin. Fetal weight gain was assessed by serial prenatal ultrasound. Malaria was assessed monthly, and Treponema pallidum, Neisseria gonorrhoeae, Trichomonas vaginalis, Chlamydia trachomatis and bacterial vaginosis at enrolment and in the third trimester. The effect of malaria and STIs/RTIs on fetal weight/birthweight Z-scores was evaluated using mixed-effects linear regression. RESULTS: 1,435 pregnant women had fetal/birth weight assessed 3,950 times. Compared to women without malaria or STIs/RTIs (n=399), malaria-only (n=267), STIs/RTIs-only (n=410) or both (n=353) were associated with reduced fetal growth (adjusted mean difference in fetal/birth weight Z-score [95% CI]: malaria=-0.18 [-0.31,-0.04], p=0.01]; STIs/RTIs=-0.14 [-0.26,-0.03], p=0.01]; both=-0.20 [-0.33,-0.07], p=0.003). Paucigravidae experienced the greatest impact. CONCLUSION: Malaria and STIs/RTIs are associated with poor fetal growth especially among paucigravidae women with dual infections. Integrated antenatal interventions are needed to reduce the burden of both malaria and STIs/RTIs. |
The Impact of Antimalarial Resistance on the Genetic Structure of Plasmodium falciparum in the DRC (preprint)
Verity R , Aydemir O , Brazeau NF , Watson OJ , Hathaway NJ , Mwandagalirwa MK , Marsh PW , Thwai K , Fulton T , Denton M , Morgan AP , Parr JB , Tumwebaze PK , Conrad M , Rosenthal PJ , Ishengoma DS , Ngondi J , Gutman J , Mulenga M , Norris DE , Moss WJ , Mensah BA , Myers-Hansen JL , Ghansah A , Tshefu AK , Ghani AC , Meshnick SR , Bailey JA , Juliano JJ . bioRxiv 2019 656561 The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequenced 2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a novel high-throughput genotyping tool. We identified an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identified highly related parasites over large geographic distances, indicative of gene flow and migration. Our results were consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations. |
Fetal sex and risk of pregnancy-associated malaria in Plasmodium falciparum-endemic regions: a meta-analysis
Unger HW , Hadiprodjo AJ , Gutman JR , Briand V , Fievet N , Valea I , Tinto H , D'Alessandro U , Landis SH , Ter Kuile F , Ouma P , Oneko M , Mwapasa V , Slutsker L , Terlouw DJ , Kariuki S , Ayisi J , Nahlen B , Desai M , Madanitsa M , Kalilani-Phiri L , Ashorn P , Maleta K , Tshefu-Kitoto A , Mueller I , Stanisic D , Cates J , Van Eijk AM , Ome-Kaius M , Aitken EH , Rogerson SJ . Sci Rep 2023 13 (1) 10310 In areas of moderate to intense Plasmodium falciparum transmission, malaria in pregnancy remains a significant cause of low birth weight, stillbirth, and severe anaemia. Previously, fetal sex has been identified to modify the risks of maternal asthma, pre-eclampsia, and gestational diabetes. One study demonstrated increased risk of placental malaria in women carrying a female fetus. We investigated the association between fetal sex and malaria in pregnancy in 11 pregnancy studies conducted in sub-Saharan African countries and Papua New Guinea through meta-analysis using log binomial regression fitted to a random-effects model. Malaria infection during pregnancy and delivery was assessed using light microscopy, polymerase chain reaction, and histology. Five studies were observational studies and six were randomised controlled trials. Studies varied in terms of gravidity, gestational age at antenatal enrolment and bed net use. Presence of a female fetus was associated with malaria infection at enrolment by light microscopy (risk ratio 1.14 [95% confidence interval 1.04, 1.24]; P = 0.003; n = 11,729). Fetal sex did not associate with malaria infection when other time points or diagnostic methods were used. There is limited evidence that fetal sex influences the risk of malaria infection in pregnancy. |
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