To enhance malaria elimination, Vietnam adopted a Reactive Surveillance and Response (RASR) Strategy in which malaria case notification and investigation must be completed within 2 days followed by a ...focus investigation within 7 days. The nationwide performance of Vietnam's RASR strategy has yet to be evaluated. This study aims to evaluate the performance and feasibility of RASR in Vietnam, thereby providing recommendations for improved RASR.
To assess malaria RASR in Vietnam, a mixed-methods study of (1) secondary data analysis of nationwide malaria case-based dataset from 2017 to 2021; (2) a quantitative survey, and (3) qualitative in-depth interviews and focus group discussions administered to central, provincial and district level stakeholders/staff and to the commune and community level front line health services providers was conducted.
In Vietnam, there are guidelines and procedures for implementation of each step of RASR. The completeness of case notification on the reported monthly aggregated data was very high in both the paper-based (12,463/12,498, 99.7% in 2017-2020) and electronic reporting systems (467/467, 100% in 2021 when electronic reporting was introduced); however, there were delays in notification while using the paper-based system (timely notification-7,978/12,498, 63.8%). In 2021, the completeness (453/467, 97.0%) and timeliness (371/467, 79.4%) of case investigation were found to be high. Reactive case detection was the major focus investigation response, with fever screening achievement of 88.6% (11,481 / 12,965) and 88.5% (11,471 / 12,965) among index case and neighbouring household members, respectively.
Overall, there was policy commitment for implementation of RASR in Vietnam. The completeness and timeliness of case notification and case investigation were high and improved after the introduction of the electronic reporting system. More evidence is required for reactive case detection in defining the screening area or population.
Differences in acquisition and boosting of anti‐malarial antibodies among African children exposed to malaria.
Antibodies play a key role in acquired human immunity to Plasmodium falciparum (Pf) ...malaria and target merozoites to reduce or prevent blood‐stage replication and the development of disease. Merozoites present a complex array of antigens to the immune system, and currently, there is only a partial understanding of the targets of protective antibodies and how responses to different antigens are acquired and boosted. We hypothesized that there would be differences in the rate of acquisition of antibodies to different antigens and how well they are boosted by infection, which impacts the acquisition of immunity. We examined responses to a range of merozoite antigens in 2 different cohorts of children and adults with different age structures and levels of malaria exposure. Overall, antibodies were associated with age, exposure, and active infection, and the repertoire of responses increased with age and active infection. However, rates of antibody acquisition varied between antigens and different regions within an antigen following exposure to malaria, supporting our hypothesis. Antigen‐specific responses could be broadly classified into early response types in which antibodies were acquired early in childhood exposure and late response types that appear to require substantially more exposure for the development of substantial levels. We identified antigen‐specific responses that were effectively boosted after recent infection, whereas other responses were not. These findings advance our understanding of the acquisition of human immunity to malaria and are relevant to the development of malaria vaccines targeting merozoite antigens and the selection of antigens for use in malaria surveillance.
Antibodies that inhibit the growth of blood-stage Plasmodium falciparum may play an important role in acquired and vaccine-induced immunity in humans. However, the acquisition and activity of these ...antibodies is not well understood.
We tested dialysed serum and purified immunoglobulins from Kenyan children and adults for inhibition of P. falciparum blood-stage growth in vitro using different parasite lines. Serum antibodies were measured by ELISA to blood-stage parasite antigens, extracted from P. falciparum schizonts, and to recombinant merozoite surface protein 1 (42 kDa C-terminal fragment, MSP1-42).
Antibodies to blood-stage antigens present in schizont protein extract and to recombinant MSP1-42 significantly increased with age and were highly correlated. In contrast, growth-inhibitory activity was not strongly associated with age and tended to decline marginally with increasing age and exposure, with young children demonstrating the highest inhibitory activity. Comparison of growth-inhibitory activity among samples collected from the same population at different time points suggested that malaria transmission intensity influenced the level of growth-inhibitory antibodies. Antibodies to recombinant MSP1-42 were not associated with growth inhibition and high immunoglobulin G levels were poorly predictive of inhibitory activity. The level of inhibitory activity against different isolates varied.
Children can acquire growth-inhibitory antibodies at a young age, but once they are acquired they do not appear to be boosted by on-going exposure. Inhibitory antibodies may play a role in protection from early childhood malaria.
In recent years several new fastidious bacteria have been identified that display a high specificity for BV; however no previous studies have comprehensively assessed the behavioural risk ...associations of these bacterial vaginosis-candidate organisms (BV-COs).
We examined the associations between 8 key previously described BV-COs and BV status established by Nugent's score (NS). We also examined the sexual practices associated with each BV-CO. We incorporated 2 study populations: 193 from a sexually-inexperienced university population and 146 from a highly sexually-active clinic population. Detailed behavioural data was collected by questionnaire and vaginal smears were scored by the Nugent method. Stored samples were tested by quantitative PCR assays for the 8 BV-COs: Atopobium vaginae, Gardnerella vaginalis, Leptotrichia spp., Megasphaera type I, Sneathia spp., and the Clostridia-like bacteria BVAB1, BVAB2 and BVAB3. Associations between BV-COs and BV and behaviours were examined by univariate and multivariable analyses.
On univariate analysis, all BV-COs were more common in BV compared to normal flora. However, only Megasphaera type I, BVAB2, A. vaginae and G. vaginalis were significantly independently associated with BV by multivariable analysis. Six of the eight BV-COs (Megasphaera type I, BVAB2, BVAB3, Sneathia, Leptotrichia and G. vaginalis) were rare or absent in sexually-unexposed women, and demonstrated increasing odds of detection with increasing levels of sexual activity and/or numbers of lifetime sexual partners. Only G. vaginalis and A. vaginae were commonly detected in sexually-unexposed women. Megasphaera type I was independently associated with women-who-have-sex-with women (WSW) and lifetime sexual partner numbers, while unprotected penile-vaginal-sex was associated with BVAB2 detection by multivariate analysis.
Four of eight key BV-COs were significantly associated with BV after adjusting for the presence of other BV-COs. The majority of BV-COs were absent or rare in sexually-unexposed women, and associated with increasing sexual exposure, suggesting potential sexual transmission of BV-COs.
Although global efforts in the past decade have halved the number of deaths due to malaria, there are still an estimated 219 million cases of malaria a year, causing more than half a million deaths. ...In this forum article, we asked experts working in malaria research and control to discuss the ways in which malaria might eventually be eradicated. Their collective views highlight the challenges and opportunities, and explain how multi-factorial and integrated processes could eventually make malaria eradication a reality.
Antibodies targeting blood stage antigens are important in protection against malaria, but the key targets and mechanisms of immunity are not well understood. Merozoite surface protein 1 (MSP1) is an ...abundant and essential protein. The C-terminal 19 kDa region (MSP1-19) is regarded as a promising vaccine candidate and may also be an important target of immunity.
Growth inhibitory antibodies against asexual-stage parasites and IgG to recombinant MSP1-19 were measured in plasma samples from a longitudinal cohort of 206 children in Papua New Guinea. Differential inhibition by samples of mutant P. falciparum lines that expressed either the P. falciparum or P. chabaudi form of MSP1-19 were used to quantify MSP1-19 specific growth-inhibitory antibodies. The great majority of children had detectable IgG to MSP1-19, and high levels of IgG were significantly associated with a reduced risk of symptomatic P. falciparum malaria during the 6-month follow-up period. However, there was little evidence of PfMSP1-19 specific growth inhibition by plasma samples from children. Similar results were found when testing non-dialysed or dialysed plasma, or purified antibodies, or when measuring growth inhibition in flow cytometry or microscopy-based assays. Rabbit antisera generated by immunization with recombinant MSP1-19 demonstrated strong MSP1-19 specific growth-inhibitory activity, which appeared to be due to much higher antibody levels than human samples; antibody avidity was similar between rabbit antisera and human plasma.
These data suggest that MSP1-19 is not a major target of growth inhibitory antibodies and that the protective effects of antibodies to MSP1-19 are not due to growth inhibitory activity, but may instead be mediated by other mechanisms. Alternatively, antibodies to MSP1-19 may act as a marker of protective immunity.
Entomological surveillance for malaria is inherently resource-intensive and produces crude population-level measures of vector exposure which are insensitive in low-transmission settings. Antibodies ...against
salivary proteins measured at the individual level may serve as proxy biomarkers for vector exposure and malaria transmission, but their relationship is yet to be quantified.
A systematic review of studies measuring antibodies against
salivary antigens (PROSPERO: CRD42020185449). Multilevel modelling (to account for multiple study-specific observations level 1, nested within study level 2, and study nested within country level 3) estimated associations between seroprevalence with
human biting rate (HBR) and malaria transmission measures.
From 3981 studies identified in literature searches, 42 studies across 16 countries were included contributing 393 study-specific observations of anti-
salivary antibodies determined in 42,764 samples. A positive association between HBR (log transformed) and seroprevalence was found; overall a twofold (100% relative) increase in HBR was associated with a 23% increase in odds of seropositivity (OR: 1.23, 95% CI: 1.10-1.37; p<0.001). The association between HBR and
salivary antibodies was strongest with concordant, rather than discordant,
species. Seroprevalence was also significantly positively associated with established epidemiological measures of malaria transmission: entomological inoculation rate,
spp. prevalence, and malarial endemicity class.
salivary antibody biomarkers can serve as a proxy measure for HBR and malaria transmission, and could monitor malaria receptivity of a population to sustain malaria transmission. Validation of
species-specific biomarkers is important given the global heterogeneity in the distribution of
species. Salivary biomarkers have the potential to transform surveillance by replacing impractical, inaccurate entomological investigations, especially in areas progressing towards malaria elimination.
Australian National Health and Medical Research Council, Wellcome Trust.
Abstract
Background
Strengthening surveillance systems to collect near-real-time case-based data plays a fundamental role in achieving malaria elimination in the Greater Mekong Subregion (GMS). With ...the advanced and widespread use of digital technology, mHealth is increasingly taking a prominent role in malaria surveillance systems in GMS countries, including Myanmar. In Myanmar’s malaria elimination program, an mHealth system called Malaria Case-based Reporting (MCBR) has been applied for case-based reporting of malaria data by integrated community malaria volunteers (ICMVs). However, the sustainability of such mHealth systems in the context of existing malaria elimination programs in Myanmar is unknown.
Methods
Focus group discussions were conducted with ICMVs and semi-structured in-depth interviews were conducted with malaria program stakeholders from Myanmar’s Ministry of Health and Sports and its malaria program implementing partners. Thematic (deductive followed by inductive) analysis was undertaken using a qualitative descriptive approach.
Results
Technological and financial constraints such as inadequate internet access, software errors, and insufficient financial resources to support mobile phone-related costs have hampered users’ access to MCBR. Poor system integrity, unpredictable reporting outcomes, inadequate human resources for system management, and inefficient user support undermined the perceived quality of the system and user satisfaction, and hence its sustainability. Furthermore, multiple parallel systems with functions overlapping those of MCBR were in use.
Conclusions
Despite its effectiveness and efficiency in malaria surveillance, the sustainability of nationwide implementation of MCBR is uncertain. To make it sustainable, stakeholders should deploy a dedicated human workforce with the necessary technical and technological capacities; secure sustainable, long-term funding for implementation of MCBR; find an alternative cost-effective plan for ensuring sustainable system access by ICMVs, such as using volunteer-owned mobile phones for reporting rather than supporting new mobile phones to them; and find a solution to the burden of multiple parallel systems.
Trial registration
Not applicable.
Myanmar, a country in Greater Mekong Sub-region, aims to eliminate malaria by 2030. To achieve malaria elimination, Myanmar adopted a reactive surveillance and response strategy of malaria case ...notification within 1 day and case investigation, foci investigation and response activities within 7 days. A literature review was conducted to gain a better understanding of how the reactive surveillance and response strategies are being implemented in Myanmar including enablers and barriers to their implementation. Only two assessments of the completeness and timeliness of reactive surveillance and response strategy in Myanmar have been published to date. The proportion of positive cases notified within one day was 27.9% and the proportion of positive cases investigated within 7 days as recommended by the national guidelines varied from 32.5 to 91.8% under different settings in reported studies. Strong collaboration between the National Malaria Control Programme and implementing partners, and adequate human resource and financial support contributed to a successful and timely implementation of reactive surveillance and response strategy. Documented enablers for successful implementation of reactive surveillance and response strategy included frontline health workers having good knowledge of reactive surveillance and response activities and availability of Basic Health Staff for timely implementation of foci response activities. Barriers for implementation of reactive surveillance and response activities were also identified, including shortage of human resources especially in hard-to-reach settings, limited mobile phone network services and internet coverage leading to delays in timely notification of malaria cases, lengthy and complex case investigation forms and different reporting systems between Basic Health Staff and volunteers.
Summary Background Artemisinins, the most effective antimalarials available, are not recommended for falciparum malaria during the first trimester of pregnancy because of safety concerns. Therefore, ...quinine is used despite its poor effectiveness. Assessing artemisinin safety requires weighing the risks of malaria and its treatment. We aimed to assess the effect of first-trimester malaria and artemisinin treatment on miscarriage and major congenital malformations. Methods In this observational study, we assessed data from antenatal clinics on the Thai–Myanmar border between Jan 1, 1994, and Dec 31, 2013. We included women who presented to antenatal clinics during their first trimester with a viable fetus. Women were screened for malaria, and data on malaria, antimalarial treatment, and birth outcomes were collected. The relationship between artemisinin treatments (artesunate, dihydroartemisinin, or artemether) and miscarriage or malformation was assessed using Cox regression with left-truncation and time-varying exposures. Findings Of 55 636 pregnancies registered between 1994 and 2013, 25 485 pregnancies were analysed for first-trimester malaria and miscarriage, in which 2558 (10%) had first-trimester malaria. The hazard of miscarriage increased 1·61-fold after an initial first-trimester falciparum episode (95% CI 1·32–1·97; p<0·0001), 3·24-fold following falciparum recurrence (2·24–4·68; p<0·0001), and 2·44-fold (1·01–5·88; p=0·0473) following recurrent symptomatic vivax malaria. No difference was noted in miscarriage in first-line falciparum treatments with artemisinin (n=183) versus quinine (n=842; HR 0·78 95% CI 0·45–1·34; p=0·3645) or in risk of major congenital malformations (two 2% of 109 95% CI 0·22–6·47 versus eight (1%) of 641 0·54–2·44, respectively). Interpretation First-trimester falciparum and vivax malaria both increase the risk of miscarriage. We noted no evidence of an increased risk of miscarriage or of major congenital malformations associated with first-line treatment with an artemisinin derivative compared with quinine. In view of the low efficacy of quinine and wide availability of highly effective artemisinin-based combination therapies, it is time to reconsider first-trimester antimalarial treatment recommendations. Funding The Wellcome Trust and The Bill & Melinda Gates Foundation.
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