The World Malaria Report, released in December 2021, reflects the unique challenges currently facing the global malaria community. The report showed the devastating toll of malaria, with an estimated ...627,000 people losing their lives to the disease in 2020. The improved methodological approach used for calculating cause of death for young children revealed a systematic underestimation of disease burden over the past two decades; and that Africa has an even greater malaria crisis than previously known. While countries were able to prevent the worst-case scenarios, the disruptions due to the COVID-19 pandemic revealed how weak health systems and inadequate financing can limit the capacity of the continent to address the malaria challenge. African countries also face a convergence of biological threats that could redefine malaria control, notably widespread pyrethroid resistance and emerging resistance to artemisinin. Despite these challenges, there is cause for optimism in lessons learned from the COVID-19 pandemic, recent acceleration of cutting edge research and development, and new partnerships that encourage leadership from and ownership by affected countries. This article presents key insights from the 2021 World Malaria Report and reflections on the future trajectories: it was informed by an in-depth discussion with leading malaria experts from the World Health Organization (WHO), the Bill & Melinda Gates Foundation, and the U.S. President's Malaria Initiative (PMI). The discussion took place during the 34th edition of the Ifakara Master Classes, held virtually on December 15th, 2021.
Virtually all women who have cervical cancer are infected with the human papillomavirus (HPV). Of the 275,000 women who die from cervical cancer every year, 88% live in developing countries. Two ...vaccines against the HPV have been approved. However, vaccine implementation in low-income countries tends to lag behind implementation in high-income countries by 15 to 20 years.
In 2011, Rwanda's Ministry of Health partnered with Merck to offer the Gardasil HPV vaccine to all girls of appropriate age. The Ministry formed a "public-private community partnership" to ensure effective and equitable delivery.
Thanks to a strong national focus on health systems strengthening, more than 90% of all Rwandan infants aged 12-23 months receive all basic immunizations recommended by the World Health Organization.
In 2011, Rwanda's HPV vaccination programme achieved 93.23% coverage after the first three-dose course of vaccination among girls in grade six. This was made possible through school-based vaccination and community involvement in identifying girls absent from or not enrolled in school. A nationwide sensitization campaign preceded delivery of the first dose.
Through a series of innovative partnerships, Rwanda reduced the historical two-decade gap in vaccine introduction between high- and low-income countries to just five years. High coverage rates were achieved due to a delivery strategy that built on Rwanda's strong vaccination system and human resources framework. Following the GAVI Alliance's decision to begin financing HPV vaccination, Rwanda's example should motivate other countries to explore universal HPV vaccine coverage, although implementation must be tailored to the local context.
Against a backdrop of stalled progress in malaria control, it is surprising that the various forms of malaria chemoprevention are not more widely used. The World Health Organization (WHO) has ...recommended several malaria chemoprevention strategies, some of them for over a decade, and each with documented efficacy and cost effectiveness. In 2022, the WHO updated and augmented its malaria chemoprevention guidelines to facilitate their wider use. This paper considers new insights into the empirical evidence that supports the broader application of chemoprevention and encourages its application as a default strategy for young children living in moderate to high transmission settings given their high risk of severe disease and death. Chemoprevention is an effective medium-term strategy with potential benefits far outweighing costs. There is a strong argument for urgently increasing malaria chemoprevention in endemic countries.
Rapid diagnostic tests (RDTs) for histidine rich protein 2 (HRP2) are often used to determine whether persons with fever should be treated with anti-malarials. However, Plasmodium falciparum ...parasites with a deletion of the hrp2 gene yield false-negative RDTs and there are concerns the sensitivity of HRP2-based RDTs may fall when the intensity of transmission decreases.
This observational study enrolled 9226 patients at three health centres in Rwanda from April 2014 to April 2015. It then compared the sensitivity of RDTs based on HRP2 and the Plasmodium lactate dehydrogenase (pLDH) to microscopy (thick smears) for the diagnosis of malaria. PCR was used to determine whether deletions of the histidine-rich central repeat region of the hrp2 gene (exon 2) were associated with false-negative HRP2-based RDTs.
In comparison to microscopy, the sensitivity and specificity of HRP2- and pLDH-based RDTs were 89.5 and 86.2% and 80.2 and 94.3%, respectively. When the results for both RDTs were combined, sensitivity rose to 91.8% and specificity was 85.7%. Additionally, when smear positivity fell from 46 to 3%, the sensitivity of the HRP2-based RDT fell from 88 to 67%. Of 370 samples with false-negative HRP2 RDT results for which PCR was performed, 140 (38%) were identified as P. falciparum by PCR. Of the isolates identified as P. falciparum by PCR, 32 (23%) were negative for the hrp2 gene based on PCR. Of the 32 P. falciparum isolates negative for hrp2 by PCR, 17 (53%) were positive based on the pLDH RDT.
This prospective study of RDT performance coincided with a decline in the intensity of malaria transmission in Kibirizi (fall in slide positivity from 46 to 3%). This decline was associated with a decrease in HRP2 RDT sensitivity (from 88 to 67%). While P. falciparum isolates without the hrp2 gene were an important cause of false-negative HRP2-based RDTs, most were identified by the pLDH-based RDT. Although WHO does not recommend the use of combined HRP2/pLDH testing in sub-Saharan Africa, these results suggest that combination HRP2/pLDH-based RDTs could reduce the impact of false-negative HRP2-based RDTs for detection of symptomatic P. falciparum malaria.
An increasing number of malaria-endemic African countries are rapidly scaling up malaria prevention and treatment. To have an initial estimate of the impact of these efforts, time trends in health ...facility records were evaluated in selected districts in Ethiopia and Rwanda, where long-lasting insecticidal nets (LLIN) and artemisinin-based combination therapy (ACT) had been distributed nationwide by 2007.
In Ethiopia, a stratified convenience sample covered four major regions where (moderately) endemic malaria occurs. In Rwanda, two districts were sampled in all five provinces, with one rural health centre and one rural hospital selected in each district. The main impact indicator was percentage change in number of in-patient malaria cases and deaths in children < 5 years old prior to (2001-2005/6) and after (2007) nationwide implementation of LLIN and ACT.
In-patient malaria cases and deaths in children < 5 years old in Rwanda fell by 55% and 67%, respectively, and in Ethiopia by 73% and 62%. Over this same time period, non-malaria cases and deaths generally remained stable or increased.
Initial evidence indicated that the combination of mass distribution of LLIN to all children < 5 years or all households and nationwide distribution of ACT in the public sector was associated with substantial declines of in-patient malaria cases and deaths in Rwanda and Ethiopia. Clinic-based data was a useful tool for local monitoring of the impact of malaria programmes.
Malaria was first reported in Rwanda in the early 1900s with significant heterogeneity and volatility in transmission over subsequent decades. Here, a comprehensive literature review of malaria ...transmission patterns and control strategies in Rwanda between 1900 and 2018 is presented to provide insight into successes and challenges in the country and to inform the future of malaria control in Rwanda.
A systematic literature search of peer-reviewed publications (Web of Knowledge, PubMed, Google Scholar, and the World Health Organization Library (WHOLIS) and grey literature on malaria control in Rwanda between 1900 and 2019 was conducted with the following search terms: "malaria"", "Rwanda", "epidemiology", "control", "treatment", and/or "prevention." Reports and other relevant documents were also obtained from the Rwanda National Malaria Control Programme (NMCP). To inform this literature review and evidence synthesis, epidemiologic and intervention data were collated from NMCP and partner reports, the national routine surveillance system, and population surveys.
Two hundred sixty-eight peer-reviewed publications and 56 grey literature items were reviewed, and information was extracted. The history of malaria control in Rwanda is thematically described here according to five phases: 1900 to 1954 before the launch of the Global Malaria Eradication Programme (GMEP); (2) Implementation of the GMEP from 1955 to 1969; (3) Post- GMEP to 1994 Genocide; (4) the re-establishment of malaria control from 1995 to 2005, and (5) current malaria control efforts from 2006 to 2018. The review shows that Rwanda was an early adopter of tools and approaches in the early 2000s, putting the country ahead of the curve and health systems reforms created an enabling environment for an effective malaria control programme. The last two decades have seen unprecedented investments in malaria in Rwanda, resulting in significant declines in disease burden from 2000 to 2011. However, in recent years, these gains appear to have reversed with increasing cases since 2012 although the country is starting to make progress again.
The review shows the impact and fragility of gains against malaria, even in the context of sustained health system development. Also, as shown in Rwanda, country malaria control programmes should be dynamic and adaptive to respond and address changing settings.
Emerging artemisinin partial resistance and diagnostic resistance are a threat to malaria control in Africa. Plasmodium falciparum kelch13 (k13) propeller-domain mutations that confer artemisinin ...partial resistance have emerged in Africa. k13-561H was initially described at a frequency of 7.4% from Masaka in 2014-2015, but not present in nearby Rukara. By 2018, 19.6% of isolates in Masaka and 22% of isolates in Rukara contained the mutation. Longitudinal monitoring is essential to inform control efforts. In Rukara, an assessment was conducted to evaluate recent k13-561H prevalence changes, as well as other key mutations. Prevalence of hrp2/3 deletions was also assessed.
Samples collected in Rukara in 2021 were genotyped for key artemisinin and partner drug resistance mutations using molecular inversion probe assays and for hrp2/3 deletions using qPCR.
Clinically validated k13 artemisinin partial resistance mutations continue to increase in prevalence with the overall level of mutant infections reaching 32% in Rwanda. The increase appears to be due to the rapid emergence of k13-675V (6.4%, 6/94 infections), previously not observed, rather than continued expansion of 561H (23.5% 20/85). Mutations to partner drugs and other anti-malarials were variable, with high levels of multidrug resistance 1 (mdr1) N86 (95.5%) associated with lumefantrine decreased susceptibility and dihydrofolate reductase (dhfr) 164L (24.7%) associated with a high level of antifolate resistance, but low levels of amodiaquine resistance polymorphisms with chloroquine resistance transporter (crt) 76T: at 6.1% prevalence. No hrp2 or hrp3 gene deletions associated with diagnostic resistance were found.
Increasing prevalence of artemisinin partial resistance due to k13-561H and the rapid expansion of k13-675V is concerning for the longevity of artemisinin effectiveness in the region. False negative RDT results do not appear to be an issue with no hrp2 or hpr3 deletions detected. Continued molecular surveillance in this region and surrounding areas is needed to follow artemisinin partial resistance and provide early detection of partner drug resistance, which would likely compromise control and increase malaria morbidity and mortality in East Africa.
Artemisinin resistance (AR) emerged in South East Asia 13 years ago and the identification of the resistance conferring molecular marker, Plasmodium falciparum Kelch 13 (Pfk13), 7 years ago has ...provided an invaluable tool for monitoring AR in malaria endemic countries. Molecular Pfk13 surveillance revealed the resistance foci in the Greater Mekong Subregion, an independent emergence in Guyana, South America, and a low frequency of mutations in Africa. The recent identification of the R561H Pfk13 AR associated mutation in Tanzania, Uganda and in Rwanda, where it has been associated with delayed parasite clearance, should be a concern for the continent. In this review, we provide a summary of Pfk13 resistance associated propeller domain mutation frequencies across Africa from 2012 to 2020, to examine how many other countries have identified these mutations. Only four African countries reported a recent identification of the M476I, P553L, R561H, P574L, C580Y and A675V Pfk13 mutations at low frequencies and with no reports of clinical treatment failure, except for Rwanda. These mutations present a threat to malaria control across the continent, since the greatest burden of malaria remains in Africa. A rise in the frequency of these mutations and their spread would reverse the gains made in the reduction of malaria over the last 20 years, given the lack of new antimalarial treatments in the event artemisinin-based combination therapies fail. The review highlights the frequency of Pfk13 propeller domain mutations across Africa, providing an up-to-date perspective of Pfk13 mutations, and appeals for an urgent and concerted effort to monitoring antimalarial resistance markers in Africa and the efficacy of antimalarials by re-establishing sentinel surveillance systems.
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•Indigenous Pfk13 resistance associated mutations have been identified in Africa•Currently, only 4 African countries have reported 6 (M476I, P553L, R561H, P574L, C580Y and A675V) of the 10 validated artemisinin resistance associated mutations•The 6 mutations though identified at low frequencies are an early warning signal for Africa, since a rise in frequency and their spread to other countries could be catastrophic for malaria control•Africa needs a concerted and systematic approach to monitoring Pfk13 mutations (beyond the few research studies published across Africa) and antimalarial efficacy through a re-establishment of sentinel surveillance platforms
Rwanda has made substantial economic progress over the past two decades. However, evidence suggests that malnutrition among children remains high in spite of this progress. This study aims to examine ...trends and potential risk factors associated with childhood stunting from 2000 to 2015 in Rwanda.
Data for this study come from the 2000 to 2015 Rwanda's Demographic and Health Surveys (DHS), a cross-sectional, population-based survey that is conducted every 5 years. Following prior work, we define stunting based on age and weight as reported in the DHS. We assess the overall prevalence of stunting among children under the age of 5 in Rwanda and then conduct bivariate analyses across a range of policy-relevant demographic, socioeconomic, and health variables. We then incorporate key variables in a multivariable analysis to identify those factors that are independently associated with stunting.
The prevalence of stunting among children under the age of 5 in Rwanda declined from 2000 (47.4%) to 2015 (38.3%), though rates were relatively stagnant between 2000 and 2010. Factors associated with higher rates of stunting included living in the lowest wealth quintile, having a mother with limited education, having a mother that smoked, being of the male sex, and being of low-birth weight.
Though overall stunting rates have improved nationally, these gains have been uneven. Furthering ongoing national policies to address these disparities while also working to reduce the overall risk of malnutrition will be necessary for Rwanda to reach its overall economic and health equity goals.
The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine ...being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin derivatives have a short half-life, lumefantrine and amodiaquine may give rise to differing durations of post-treatment prophylaxis, an important additional benefit to patients in higher transmission areas.
We analyzed individual patient data from 8 clinical trials of AL versus AS-AQ in 12 sites in Africa (n = 4214 individuals). The time to PCR-confirmed reinfection after treatment was used to estimate the duration of post-treatment protection, accounting for variation in transmission intensity between settings using hidden semi-Markov models. Accelerated failure-time models were used to identify potential effects of covariates on the time to reinfection. The estimated duration of chemoprophylaxis was then used in a mathematical model of malaria transmission to determine the potential public health impact of each drug when used for first-line treatment.
We estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7-15.7) for AL and 15.2 days (95% CI 12.8-18.4) for AS-AQ overall. However, the duration varied significantly between trial sites, from 8.7-18.6 days for AL and 10.2-18.7 days for AS-AQ. Significant predictors of time to reinfection in multivariable models were transmission intensity, age, drug, and parasite genotype. Where wild type pfmdr1 and pfcrt parasite genotypes predominated (<=20% 86Y and 76T mutants, respectively), AS-AQ provided ~ 2-fold longer protection than AL. Conversely, at a higher prevalence of 86Y and 76T mutant parasites (> 80%), AL provided up to 1.5-fold longer protection than AS-AQ. Our simulations found that these differences in the duration of protection could alter population-level clinical incidence of malaria by up to 14% in under-5-year-old children when the drugs were used as first-line treatments in areas with high, seasonal transmission.
Choosing a first-line treatment which provides optimal post-treatment prophylaxis given the local prevalence of resistance-associated markers could make a significant contribution to reducing malaria morbidity.
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