Low Transmission Areas Research Articles

Evaluating the Impact of Programmatic Mass Drug Administration for Malaria in Zambia Using Routine Incidence Data.

BackgroundIn 2016, the Zambian National Malaria Elimination Centre started programmatic mass drug administration (pMDA) campaigns with dihydroartemisinin-piperaquine as a malaria elimination tool in Southern Province. Two rounds were administered, 2 months apart (coverage 70% and 57%, respectively). We evaluated the impact of 1 year of pMDA on malaria incidence using routine data.MethodsWe conducted an interrupted time series with comparison group analysis on monthly incidence data collected at the health facility catchment area (HFCA) level, with a negative binomial model using generalized estimating equations. Programmatic mass drug administration was conducted in HFCAs with greater than 50 cases/1000 people per year. Ten HFCAs with incidence rates marginally above this threshold (pMDA group) were compared with 20 HFCAs marginally below (comparison group).ResultsThe pMDA HFCAs saw a 46% greater decrease in incidence at the time of intervention than the comparison areas (incidence rate ratio = 0.536; confidence interval = 0.337–0.852); however, incidence increased toward the end of the season. No HFCAs saw a transmission interruption.ConclusionsProgrammatic mass drug administration, implemented during 1 year with imperfect coverage in low transmission areas with suboptimal vector control coverage, significantly reduced incidence. However, elimination will require additional tools. Routine data are important resources for programmatic impact evaluations and should be considered for future analyses.

Prevalence and determinants of anaemia in women of reproductive age in Sudan: analysis of a cross-sectional household survey

BackgroundAnaemia is a global health problem and women in reproductive age (WRA) are amongst the most affected population. Its consequences include low birth weight and maternal mortality. This study aimed to assess the prevalence of anaemia and to identify its determinants in Sudanese women in reproductive age.MethodsA population-based cross-sectional study was conducted in Sudan in 2016. A multi-stage stratified cluster sampling design was executed with consideration of rural population, urban population, and internally displaced persons/refugees camps residents. All women in reproductive age (15–49 years), classified by pregnancy status, in the targeted households were surveyed and personal characteristic data were collected. Their haemoglobin level and malaria infection (using rapid diagnostic test, RDT) were assessed. The World Health Organization (WHO) haemoglobin level cut-off for defining anaemia and severe anaemia in pregnant and non-pregnant women was used. Logistic regression analyses were performed.ResultsA total of 4271 women (WRA) of which 421 (9.9%) pregnant women (PW) were included in the study. The overall anaemia prevalence in WRA was 35.6%. It was 36.0 and 35.5% in PW and non-pregnant women (NPW), respectively. The average haemoglobin level was found to be 113.9 g/L (SD 16.3) and 123.2 g/L (SD 15.7) for PW and NPW respectively. Severe anaemia prevalence was 1.2% in each group. In the logistic regression model, anaemia was associated with malaria infection in PW (aOR 4.100, 95%CI 1.523–11.039, p = 0.003), NPW (aOR 2.776, 95%CI 1.889–4.080, p < 0.001), and WRA (aOR 2.885, 95%CI 2.021–4.119, p < 0.001). Other identified determinants of anaemia in NPW was living in camps (aOR 1.499, 95%CI 1.115–2.017, p = 0.007) and in WRA was being in the poorest economic class (aOR 1.436, 95%CI 1.065–1.936, p = 0.018).ConclusionsAnaemia is a public health problem in Sudan. The study supported the association between malaria infection and anaemia, but not with low and moderate malaria transmission areas. Resources need to be allocated for all anaemic populations with special attention for the populations in most need and interventions need to be implemented based on local variations. Malaria control interventions, specifically case management, may have a major impact in reducing anaemia prevalence in low to moderate malaria transmission areas.

Abstract A60: Transcriptional profile of CD56negCD16pos Natural Killer cells within endemic Burkitt lymphoma

Abstract Endemic Burkitt lymphoma (eBL), the most common pediatric cancer in equatorial Africa, has long been associated with two etiologic agents: Epstein-Barr virus (EBV) and Plasmodium falciparum malaria. On the other hand, Natural Killer (NK) cells are essential in the clearance of infected cells as well as play a critical role in tumor immunosurveillance. Despite chronic viral infections as HIV, HCV, which have been found to promote the expansion of a CD56 (negative) NK cell subset with impaired effector function, previous cancer studies have been limited to investigations of CD56dimCD16pos NK cells. We previously published that eBL children had significantly more CD56negCD16pos NK cells compared to age-matched healthy children from a low and high malaria transmission area. Here, we characterized this CD56negCD16pos NK subset using histology staining, multicolor flow cytometry, and RNA-sequencing. We found CD56negCD16pos NK cells to be morphologically similar to CD56dimCD16pos NK cells but had higher expression of FCGR3B (CD16b) (p=0.000008) and MPEG1 (Perforin 2) (p=0.0000007), and lower expression of KLRF1 (NKp80), IL18RAP and IL18R1 (IL18 receptor) (p=0.000003, p=0.000003 and p=0.00005, respectively). Phenotypically, CD56negCD16pos NK cells share characteristics of adaptive NK cells; however, they differ from “memory-like” NK cells, with consistent expression of NKG2C/CD57, lower expression of NKp46 and CD160, and higher expression of KIR3DL1 compared to CD56dimCD16pos NK cells. Finally, higher plasma levels of IL-12p70 and IL-2 (known to help NK cell activation and proliferation) and IL-6 and MIP1a were found in healthy compared to eBL children. Together, these findings suggest that the expansion of CD56negCD16pos NK cells could help explain diminished tumor immunosurveillance and might be a mechanism by which EBV-infected cells evades NK-cell mediated immunity. Citation Format: Catherine S. Forconi, Cliff Oduor, John M. Ong’echa, Jeff Bailey, Ann M. Moormann. Transcriptional profile of CD56negCD16pos Natural Killer cells within endemic Burkitt lymphoma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A60.

Treatment Coverage Estimation for Mass Drug Administration for Malaria with Dihydroartemisinin-Piperaquine in Southern Province, Zambia.

.Mass drug administration (MDA) is currently being considered as an intervention in low-transmission areas to complement existing malaria control and elimination efforts. The effectiveness of any MDA strategy is dependent on achieving high epidemiologic coverage and participant adherence rates. A community-randomized controlled trial was conducted from November 2014 to March 2016 to evaluate the impact of four rounds of MDA or focal MDA (fMDA)—where treatment was given to all eligible household members if anyone in the household had a positive malaria rapid diagnostic test—on malaria outcomes in Southern Province, Zambia (population approximately 300,000). This study examined epidemiologic coverage and program reach using capture–recapture and satellite enumeration methods to estimate the degree to which the trial reached targeted individuals. Overall, it was found that the percentage of households visited by campaign teams ranged from 62.9% (95% CI: 60.0–65.8) to a high of 77.4% (95% CI: 73.8–81.0) across four rounds of treatment. When the maximum number of visited households across all campaign rounds was used as the numerator, program reach for at least one visit would have been 86.4% (95% CI: 80.8–92.0) in MDA and 83.5% (95% CI: 78.0–89.1) in fMDA trial arms. As per the protocol, the trial provided dihydroartemisinin–piperaquine treatment to an average of 58.8% and 13.3% of the estimated population based on capture–recapture in MDA and fMDA, respectively, across the four rounds.

Identification and characterization of immature Anopheles and culicines (Diptera: Culicidae) at three sites of varying malaria transmission intensities in Uganda

BackgroundOver the last two decades, there has been remarkable progress in malaria control in sub-Saharan Africa, due mainly to the massive deployment of long-lasting insecticidal nets and indoor residual spraying. Despite these gains, it is clear that in many situations, additional interventions are needed to further reduce malaria transmission. The World Health Organization (WHO) has promoted the Integrated Vector Management (IVM) approach through its Global Vector Control Response 2017–2030. However, prior roll-out of larval source management (LSM) as part of IVM, knowledge on ecology of larval aquatic habitats is required.MethodsAquatic habitats colonized by immature Anopheles and culicines vectors were characterized at three sites of low, medium and high malaria transmission in Uganda from October 2011 to June 2015. Larval surveys were conducted along transects in each site and aquatic habitats described according to type and size. Immature Anopheles, culicines and pupae from the described habitats were sampled using standard dipping methods to determine larval and pupae densities. Larvae were identified as anopheline or culicine, and counted. Pupae were not identified further. Binary logistic regression analysis was used to identify factors associated with the presence of immature Anopheles and culicines in each site.ResultsA total of 1205 larval aquatic habitats were surveyed and yielded a total of 17,028 anopheline larvae, 26,958 culicine larvae and 1189 pupae. Peaks in larval abundance occurred in all sites in March–May and August-October coinciding with the rainy seasons. Anopheles larvae were found in 52.4% (n = 251) of aquatic habitats in Tororo, a site of high transmission, 41.9% (n = 536) of habitats in Kanungu, a site with moderate malaria transmission, and 15.8% (n = 418) in Jinja, a site with low malaria transmission. The odds of finding larvae was highest in rice fields compared to pools in both Tororo (odds ratio, OR = 4.21, 95% CI 1.22–14.56, p = 0.02) and Kanungu (OR = 2.14, 95% CI 1.12–4.07, p = 0.02), while in Jinja the odd were highest in containers (OR = 4.55, 95% CI = 1.09–19.14, p = 0.03). In Kanungu, larvae were less likely to be found in containers compared to pools (OR = 0.26, 95% CI 0.09–0.66, p = 0.008) and river fringe (OR = 0.19, 95% CI 0.07–0.52, p = 0.001). Medium sized habitats were associated with high odds of finding larvae compared to small habitats (OR = 3.59, 95% CI 1.18–14.19, p = 0.039).ConclusionsThese findings show that immature Anopheles and culicines were common in areas of high and moderate transmission but were rare in areas of low transmission. Although immature Anopheles and culicines were found in all types of water bodies, they were most common in rice fields and less common in open drains and in river fringes. Methods are needed to reduce the aquatic stages of anopheline mosquitoes in human-made habitats, particularly rice fields.

Parasite density in severe malaria in Colombia.

BackgroundColombia has officially adopted the parasite density levels of severe malaria established by the WHO (>50,000 parasites/μl). These values have been inferred from areas of high transmission in Africa and are not consistent with the dynamics of low and unstable transmission in Colombia. The objective of this study was therefore to determine the parasite density values observed in patients with severe malaria and their distribution in the different ecoepidemiological regions of Colombia.MethodsA retrospective and descriptive study of confirmed cases of severe malaria was conducted in endemic areas of malaria in Colombia over the period 2014–2017. Data were collected from secondary sources of the Subnational Programs of Malaria Prevention and Control. Person, place, and time variables were selected. The official definition of severe malaria was adopted, and compliance with these criteria was determined. Univariate and bivariate analyses were conducted with absolute and relative frequency measures, and the relevant statistical tests were applied.ResultsThe overall parasite density values in Colombia showed a geometric mean of 5,919 parasites/μl (95% CI: 5,608–6,248). By parasite species, the values were 6,151 (95% CI: 5,631–6,718) for Plasmodium falciparum and 5,815 (95% CI: 5,428–6,230) for Plasmodium vivax. The highest parasite density values were recorded in the Amazon ecoepidemiological region (8,177; 95% CI: 6,015–11,116), and the lowest values were recorded in the Andean region (5,026; 95% CI: 2,409–10,480).ConclusionsIn endemic areas of low and unstable malaria transmission in the Colombian territory, the parasite density levels observed in populations with severe malaria are lower than the officially established values. The parasite density criterion is not really a relevant criterion for the definition of severe cases in Colombia and it certainly not be used to make a clinical decision about the severity of the disease.

Emergence of Undetectable Malaria Parasites: A Threat under the Radar amid the COVID-19 Pandemic?

.Rapid diagnostic tests (RDTs) play a critical role in malaria diagnosis and control. The emergence of Plasmodium falciparum parasites that can evade detection by RDTs threatens control and elimination efforts. These parasites lack or have altered genes encoding histidine-rich proteins (HRPs) 2 and 3, the antigens recognized by HRP2-based RDTs. Surveillance of such parasites is dependent on identifying false-negative RDT results among suspected malaria cases, a task made more challenging during the current pandemic because of the overlap of symptoms between malaria and COVID-19, particularly in areas of low malaria transmission. Here, we share our perspective on the emergence of P. falciparum parasites lacking HRP2 and HRP3, and the surveillance needed to identify them amid the COVID-19 pandemic.

Low exposure to Plasmodium falciparum and Acquisition of Antibodies to Circumsporozoite Protein Antigens in Individuals Living in Western Highlands of Kenya with Unstable Malaria Transmission

Background: Malaria continues to be a major public health concern despite the concerted efforts to eliminate it. Antibodies to Plasmodium falciparum (P. falciparum) antigens are involved in prevention of infection and disease with some of the antigens being targeted as lead candidates in vaccine development. However, most of the studies have been done in malaria endemic areas with little information available on exposure and acquisition of protective antibodies in areas of low and unstable malaria transmission. This study sought to determine whether the extent of exposure to P. falciparum affect acquisition of protective antibodies by measuring antibody levels and determine the prevalence of circumsporozoite protein (CSP) and crude schizont extract (SE) in individuals living in an area with low unstable malaria transmission in Western Highlands of Kenya.Methods: Sixty plasma samples from individuals living in an area of low unstable malaria transmission in Western Highlands of Kenya were randomly selected and categorized into three age groups: 18years (n=14). Antibodies levels in plasma were measured by Enzyme Linked Immunosorbent Assay (ELISA) and compared to known positive and negative control plasma samples. Prevalence and levels of antibodies produced against circumsporozoite protein and schizont extract antigens were compared between age groups.Results. The prevalence of antibodies ranged from 0% to 14.29% at arbitrary units (AU)>2 for the two antigens. The antibody prevalence did not significantly increase with age (P>0.05) but correlated with CSP and SE antigens (r=0.5977; P<0.05).Conclusion This study highlights antibody responses to CSP and SE antigens in individuals living in low and unstable malaria transmission. The levels of antibodies were generally low across all age groups and there were no significant differences among age groups. Longitudinal study on more antigens is needed to inform exploration of multi-antigen vaccines and also adopt several control measures including Epidemic Preparedness and Response (EPR).

Malaria situation in a clear area of Iran: an approach for the better understanding of the health service providers\u2019 readiness and challenges for malaria elimination in clear areas

BackgroundMalaria mortality and morbidity have decreased in recent years. Malaria elimination (ME) and effective efforts to achieve ME is one of the most important priorities for health systems in countries in the elimination phase. In very low transmission areas, the ME programme is faced with serious challenges. This study aimed to assess the trend while getting a better understanding of Health Service Providers’ (HSPs) readiness and challenges for ME in a clear area of Iran.MethodsThis study was performed in two phases. At first, the malaria trend in East Azerbaijan Province, was surveyed from 2001 to 2018; afterward, it was compared with the national situation for a better understanding of the second phase of the study. Data were collected from the Ministry of Health’s protocol and the health centre of the province. In the second phase, malaria control programme experts, health system researchers, and health managers’ opinions were collected via in-depth interviews. They were asked regarding HSPs readiness and appropriate Malaria Case Management (MCM) in a clear area and possible challenges.ResultsA total of 135 and 154,560 cases were reported in the last 18 years in East Azerbaijan Province and Iran, respectively. The incidence rate decreased in East Azerbaijan Province from 0.4/10,000 in 2001 to zero in 2018. Furthermore, no indigenous transmission was reported for 14 years. Also, for the first time, there was no indigenous transmission in Iran in 2018. The main elicited themes of HSPs readiness through in-depth interviews were: appropriate MCM, holistic and role-playing studies for assessment of HSPs performance, system mobilization, improving identification and diagnosis of suspected cases in the first line. Similarly, the main possible challenges were found to be decreasing health system sensitivity, malaria re-introduction, and withdrawing febrile suspected cases from the surveillance chain.ConclusionHealth systems in eliminating phase should be aware that the absence of malaria cases reported does not necessarily mean that malaria is eliminated; in order to obtain valid data and to determine whether it is eliminated, holistic and role-playing studies are required. Increasing system sensitivity and mobilization are deemed important to achieve ME.

INFLUENCE OF ASYMPTOMATIC PEOPLE ON MALARIA TRANSMISSION: A MATHEMATICAL MODEL FOR A LOW-TRANSMISSION AREA CASE

Malaria remains a primary parasitic disease in the tropical world, generating high morbidity and mortality in human populations. Recently, community surveys showed a high proportion of asymptomatic cases, which are characterized by a low parasitemia and a lack of malaria symptoms. Until now, the asymptomatic population is not treated for malaria and thus remains infective for a long time. In this paper, we introduce a four-dimensional mathematical model to study the influence of asymptomatic people on malaria transmission in low-transmission areas, specifically using data from Brazil. The equilibrium points of the system are calculated, and their stability is analyzed. Via numerical simulations, more in-depth analyzes of the space of some crucial parameters on the asymptomatic population are done, such as the per capita recovery rates of symptomatic and asymptomatic people, the ratio of the density of mosquitoes to that of humans, the mortality rate of mosquitoes and the probability of undergoing asymptomatic infection upon an infectious mosquito bite. Our results indicate that the disease-free equilibrium is inside the stability region if asymptomatic people are treated and/or the ratio of the density of mosquitoes to that of humans is decreased and/or the mortality rate of mosquitoes is increased.

Identification and Pilot Evaluation of Salivary Peptides from Anopheles albimanus as Biomarkers for Bite Exposure and Malaria Infection in Colombia.

Insect saliva induces significant antibody responses associated with the intensity of exposure to bites and the risk of disease in humans. Several salivary biomarkers have been characterized to determine exposure intensity to Old World Anopheles mosquito species. However, new tools are needed to quantify the intensity of human exposure to Anopheles bites and understand the risk of malaria in low-transmission areas in the Americas. To address this need, we conducted proteomic and bioinformatic analyses of immunogenic candidate proteins present in the saliva of uninfected Anopheles albimanus from two separate colonies—one originating from Central America (STECLA strain) and one originating from South America (Cartagena strain). A ~65 kDa band was identified by IgG antibodies in serum samples from healthy volunteers living in a malaria endemic area in Colombia, and a total of five peptides were designed from the sequences of two immunogenic candidate proteins that were shared by both strains. ELISA-based testing of human IgG antibody levels against the peptides revealed that the transferrin-derived peptides, TRANS-P1, TRANS-P2 and a salivary peroxidase peptide (PEROX-P3) were able to distinguish between malaria-infected and uninfected groups. Interestingly, IgG antibody levels against PEROX-P3 were significantly lower in people that have never experienced malaria, suggesting that it may be a good marker for mosquito bite exposure in naïve populations such as travelers and deployed military personnel. In addition, the strength of the differences in the IgG levels against the peptides varied according to location, suggesting that the peptides may able to detect differences in intensities of bite exposure according to the mosquito population density. Thus, the An. albimanus salivary peptides TRANS-P1, TRANS-P2, and PEROX-P3 are promising biomarkers that could be exploited in a quantitative immunoassay for determination of human-vector contact and calculation of disease risk.

A panel of recombinant proteins from human-infective Plasmodium species for serological surveillance

BackgroundMalaria remains a global health problem and accurate surveillance of Plasmodium parasites that are responsible for this disease is required to guide the most effective distribution of control measures. Serological surveillance will be particularly important in areas of low or periodic transmission because patient antibody responses can provide a measure of historical exposure. While methods for detecting host antibody responses to Plasmodium falciparum and Plasmodium vivax are well established, development of serological assays for Plasmodium knowlesi, Plasmodium ovale and Plasmodium malariae have been inhibited by a lack of immunodiagnostic candidates due to the limited availability of genomic information.MethodsUsing the recently completed genome sequences from P. malariae, P. ovale and P. knowlesi, a set of 33 candidate cell surface and secreted blood-stage antigens was selected and expressed in a recombinant form using a mammalian expression system. These proteins were added to an existing panel of antigens from P. falciparum and P. vivax and the immunoreactivity of IgG, IgM and IgA immunoglobulins from individuals diagnosed with infections to each of the five different Plasmodium species was evaluated by ELISA. Logistic regression modelling was used to quantify the ability of the responses to determine prior exposure to the different Plasmodium species.ResultsUsing sera from European travellers with diagnosed Plasmodium infections, antigens showing species-specific immunoreactivity were identified to select a panel of 22 proteins from five Plasmodium species for serological profiling. The immunoreactivity to the antigens in the panel of sera taken from travellers and individuals living in malaria-endemic regions with diagnosed infections showed moderate power to predict infections by each species, including P. ovale, P. malariae and P. knowlesi. Using a larger set of patient samples and logistic regression modelling it was shown that exposure to P. knowlesi could be accurately detected (AUC = 91%) using an antigen panel consisting of the P. knowlesi orthologues of MSP10, P12 and P38.ConclusionsUsing the recent availability of genome sequences to all human-infective Plasmodium spp. parasites and a method of expressing Plasmodium proteins in a secreted functional form, an antigen panel has been compiled that will be useful to determine exposure to these parasites.

The hidden Plasmodium malariae in blood donors: a risk coming from areas of low transmission of malaria.

ABSTRACTMalaria is an infectious vector-borne disease with other important routes of transmission, such as blood transfusion and organ/tissue transplantation, due to asymptomatic reservoirs of Plasmodium presenting with low parasitemia. Reports of transfusion-transmitted malaria have shown that in immunosuppressed recipients, infections can be fatal if they are not diagnosed and timely treated. All Plasmodium species can survive on blood components at temperatures from 2 to 6 °C for some days or even weeks. This report describes two candidates for blood donation harboring Plasmodium, infected in an area considered non-endemic. Blood samples were collected from donors who attended a blood bank in Sao Paulo and tested by microscopy, qPCR for Plasmodium genus-specific amplification, targeting the parasite 18S ribosomal subunit gene and a multiplex qPCR based on mtDNA of the five species. Under microscopy, only structures resembling Plasmodium were observed. The qPCR whose standard curve tested parasites varying from 2 to 0.1 parasites/ µL, showed the presence of Plasmodium DNA in the two blood donors, as did the multiplex qPCR that revealed the presence of P. malariae. The prevalence of positive donors varies according to the level of transmission, ranging from 0.7 to 55% in endemic areas. In non-endemic regions, prevalences are lower, however, transfusion malaria can evolve to severe cases, due to the lack of suspicion of this transmission route. Asymptomatic donors from low transmission regions pose a risk to blood banks, with particular emphasis on those located in areas with malaria elimination goals.

Rolling back malaria in Africa - challenges and opportunities to winning the elimination battle.

A high-level review was conducted of the literature pertaining to the challenges and opportunities for eliminating malaria on the African continent. Although malaria mortality and morbidity are on the decline, the disease remains one of public health importance. Africa has invariably borne the brunt of the disease, recording the highest number of cases and deaths. However, with greater emphasis being placed on the disease by the international community, partnerships have developed to boost malaria elimination efforts on the continent. One such initiative is the Roll Back Malaria (RBM) partnership which aims to facilitate malaria elimination through increasing resources and awareness. Many cross-border initiatives have been established which treat malaria as a regional problem rather than a country-specific one. Accelerated malaria control efforts have led to a 37% decrease in cases and 60% reduction in deaths. Multi-country efforts have resulted in marked reductions of transmission in the region. Although there have been noteworthy gains in curtailing the disease, new challenges have arisen. The main among these are residual malaria and outdoor biting. One of the main drivers of residual malaria is insecticide resistance. Adding to the burden of residual transmission is the discovery of new vectors that may exist at low densities. To exacerbate these issues is the challenge of malaria imported from high- to low-transmission areas. Nevertheless, compared with the historical picture, we are winning the battle against malaria. Countries in Africa are being certified malaria-free. Partnerships have been developed to take forward the RBM Global Malaria Action Plan. Elimination agendas can only be successful if funding remains sustainable, with greater reliance on domestic funding.

The persistence of naturally acquired antibodies and memory B cells specific to rhoptry proteins of Plasmodium vivax in patients from areas of low malaria transmission

BackgroundRhoptries are the large, paired, secretory organelles located at the apical tip of the malaria merozoite that are considered important for parasite invasion processes. Plasmodium vivax rhoptry proteins have been shown to induce humoral immunity during natural infections. Therefore, these proteins may be potential novel vaccine candidates. However, there is a lack of data on the duration of antibody and memory B cell (MBC) responses. Here, the longitudinal analysis of antibody and MBC responses to the P. vivax rhoptry proteins PvRALP1-Ecto and PvRhopH2 were monitored and analysed in individuals to determine their persistence.MethodsThirty-nine samples from P. vivax-infected subjects (age 18–60 years) were recruited to explore the frequency and persistence of antibody and MBC responses against rhoptry proteins (PvRALP1-Ecto and PvRhopH2) using both cross-sectional and longitudinal cohort study designs. Antibody levels were determined by ELISA during clinical malaria, and at 3, 9 and 12 months post-infection. The frequency of MBC sub-sets and presence of rhoptry-specific MBCs in subjects 18 months after treatment were detected by flow cytometry and ELISPOT assay.ResultsThe seroprevalence of antibodies against PvRALP1-Ecto and PvRhopH2 proteins was found to be high during acute infection, with IgG1, IgG2 and IgG3 sub-classes predominant. However, these anti-rhoptry responses were short-lived and significantly decreased at 9 months post-infection. To relate the durability of these antibody responses to MBC persistence at post-infection, 18-month post-infection peripheral blood mononuclear cells (PBMCs) samples were taken to detect rhoptry-specific MBCs and frequency of MBC sub-sets, and correlate with antibody responses. These late post-infection samples revealed that rhoptry-specific MBCs were present in about 70% of total subjects. However, the persistence of specific MBCs was not correlated with antibody responses as the majority of malaria subjects who were positive for PvRALP1-Ecto- or PvRhopH2-specific MBCs were seronegative for the rhoptry antigens. The frequencies of classical MBCs were increased after infection, whereas those of activated and atypical MBCs were decreased, indicating that MBC responses could switch from activated or atypical MBCs to classical MBCs after parasite clearance, and were maintained in blood circulating at post-infection.ConclusionThe study showed that rhoptry antigens induced the development and persistence of MBC responses in P. vivax-infected subjects who lived in a region of low malaria transmission, which were not related to the longevity of antibody responses.

Estimating malaria burden among pregnant women using data from antenatal care centres in Tanzania: a population-based study

BackgroundMore timely estimates of malaria prevalence are needed to inform optimal control strategies and measure progress. Since 2014, Tanzania has implemented nationwide malaria screening for all pregnant women within the antenatal care system. We aimed to compare malaria test results during antenatal care to two population-based prevalence surveys in Tanzanian children aged 6–59 months to examine their potential in measuring malaria trends and progress towards elimination.MethodsMalaria test results from pregnant women screened at their first antenatal care visits at health-care facilities (private and public) in all 184 districts of Tanzania between Jan 1, 2014, and Dec 31, 2017, were collected from the Health Management Information Systems and District Health Information System 2. We excluded facilities with no recorded antenatal care attendees during the time period. We standardised results to account for testing uptake and weighted them by the timing of two population-based surveys of childhood malaria prevalence done in 2015–16 (Demographic and Health Survey) and 2017 (Malaria Indicator Survey). We assessed regional-level correlation using Spearman’s coefficient and assessed the consistency of monthly district-level prevalence ranking using Kendall’s correlation coefficient.FindingsCorrelation between malaria prevalence at antenatal care and among children younger than 5 years was high (r≥0·83 for both surveys), although declines in prevalence at antenatal care were generally smaller than among children. Consistent heterogeneity (p<0·05) in antenatal care prevalence at the district level was evident in all but one region (Kilimanjaro). Data from antenatal care showed declining prevalence in three regions (Arusha, Kilimanjaro, and Manyara) where surveys estimated zero prevalence.InterpretationRoutine antenatal care-based screening can be used to assess heterogeneity in transmission at finer resolution than population-based surveys, and provides sample sizes powered to detect changes, notably in areas of low transmission where surveys lack power. Declines in prevalence at antenatal care might lag behind those among children, highlighting the value of monitoring burden and continuing prevention efforts among pregnant women as transmission declines. The pregnancy-specific benefits and cost-effectiveness of antenatal care-based screening remain to be assessed.

The usefulness of indirect diagnostic tests for Schistosoma haematobium infection after repeated rounds of mass treatment with praziquantel in Mpwapwa and Chakechake districts in Tanzania

BackgroundIndirect diagnostic tests are used to assess the disease burden and to monitor the impact of different interventions in areas endemic for urinary schistosomiasis. This study was performed to assess their accuracy in the diagnosis of urinary schistosomiasis among primary school children in low and moderate transmission areas in the districts of Mpwapwa and Chakechake, respectively. MethodsSchool children were interviewed regarding their history of haematuria and participation in treatment campaigns. Urine samples were collected and inspected for macro-haematuria (visual haematuria) and tested for micro-haematuria using urine reagent strips and Schistosoma haematobium eggs by urine filtration method. ResultsThe prevalence of S. haematobium was 6.8% in Mtera Dam area and 38.7% in Uwandani Shehia. In Mtera Dam area, a history of haematuria and visual haematuria had low sensitivity (<60%) with high specificity (>90%). The urine reagent strips had high sensitivity and specificity (≥75%). In Uwandani Shehia, a history of haematuria had high sensitivity and specificity (>60%). Visual haematuria had low sensitivity (<50%) but high specificity (>80%). The urine reagent strips maintained high performance in all parameters assessed. ConclusionsThe study findings suggest that urine reagent strips will continue to serve as a very useful adjunct test for monitoring the prevalence of urinary schistosomiasis in endemic areas.

Field performance of the malaria highly sensitive rapid diagnostic test in a setting of varying malaria transmission

BackgroundThe Gambia has successfully reduced malaria transmission. The human reservoir of infection could further decrease if malaria-infected individuals could be identified by highly sensitive, field-based, diagnostic tools and then treated.MethodsA cross-sectional survey was done at the peak of the 2017 malaria season in 47 Gambian villages. From each village, 100 residents were randomly selected for finger-prick blood samples to detect Plasmodium falciparum infections using highly sensitive rapid diagnostic tests (HS-RDT) and PCR. The sensitivity and specificity of the HS-RDT were estimated (assuming PCR as the gold standard) across varying transmission intensities and in different age groups. A deterministic, age-structured, dynamic model of malaria transmission was used to estimate the impact of mass testing and treatment (MTAT) with HS-RDT in four different scenarios of malaria prevalence by PCR: 5, 15, 30, and 60%, and with seasonal transmission. The impact was compared both to MTAT with conventional RDT and mass drug administration (MDA).ResultsMalaria prevalence by HS-RDT was 15% (570/3798; 95% CI 13.9–16.1). The HS-RDT sensitivity and specificity were 38.4% (191/497, 95% CI 34.2–42.71) and 88.5% (2922/3301; 95% CI 87.4–89.6), respectively. Sensitivity was the highest (50.9%, 95% CI 43.3–58.5%) in high prevalence villages (20–50% by PCR). The model predicted that in very low transmission areas (≤ 5%), three monthly rounds of MTAT with HS-RDT, starting towards the end of the dry season and testing 65 or 85% of the population for 2 consecutive years, would avert 62 or 78% of malaria cases (over 2 years), respectively. The effect of the intervention would be lower in a moderate transmission setting. In all settings, MDA would be superior to MTAT with HS-RDT which would be superior to MTAT with conventional RDT.ConclusionThe HS-RDT’s field sensitivity was modest and varied by transmission intensity. In low to very low transmission areas, three monthly rounds per year of MTAT with HS-RDT at 85% coverage for 2 consecutive years would reduce malaria prevalence to such low levels that additional strategies may achieve elimination. The model prediction would need to be confirmed by cluster-randomized trials.

Socioeconomic determinants of community knowledge and practice in relation to malaria in high- and low-transmission areas of central India.

This study was undertaken with an aim of exploring community knowledge and treatment practices related to malaria and their determinants in high- and low-transmission areas of central India. A community-based cross-sectional study was carried out between August 2015 and January 2016 in two high- and two low-malaria-endemic districts of central India. A total of 1470 respondents were interviewed using a pre-tested structured interview schedule. Respondents residing in high-transmission areas with higher literacy levels, and of higher socioeconomic status, were found to practise more modern preventive measures than those living in low-transmission areas with low literacy levels and who were economically poor. Level of literacy, socioeconomic status and area (district) of residence were found to be the main factors affecting people's knowledge of malaria aetiology and clinical features, and prevention and treatment practices, in this community in central India.

Safety and tolerability of single low-dose primaquine in a low-intensity transmission area in South Africa: an open-label, randomized controlled trial

BackgroundTo reduce onward falciparum malaria transmission, the World Health Organization recommends adding single low-dose (SLD) primaquine to artemisinin-based combination treatment in low transmission areas. However, uptake of this recommendation has been relatively slow given concerns about whether individual risks justify potential community benefit. This study was undertaken to generate comprehensive local data on the risk–benefit profile of SLD primaquine deployment in a pre-elimination area in South Africa.MethodsThis randomized, controlled open-label trial investigated adding a single low primaquine dose on day 3 to standard artemether–lumefantrine treatment for uncomplicated falciparum malaria. Efficacy, safety and tolerability of artemether–lumefantrine and primaquine treatment were assessed on days 3, 7, 14, 28 and 42. Lumefantrine concentrations were assayed from dried blood spot samples collected on day 7.ResultsOf 217 patients screened, 166 were enrolled with 140 randomized on day 3, 70 to each study arm (primaquine and no primaquine). No gametocytes were detected by either microscopy or PCR in any of the follow-up samples collected after randomization on day 3, precluding assessment of primaquine efficacy. Prevalence of the CYP2D6*4, CYP2D6*10 and CYP2D6*17 mutant alleles was low with allelic frequencies of 0.02, 0.11 and 0.16, respectively; none had the CYP2D6*4/*4 variant associated with null activity. Among 172 RDT-positive patients G6PD-genotyped, 24 (14%) carried the G6PD deficient (A−) variant. Median haemoglobin concentrations were similar between treatment arms throughout follow-up. A third of participants had a haemoglobin drop > 2 g/dL; this was not associated with primaquine treatment but may be associated with G6PD genotype [52.9% (9/17) with A− genotype vs. 31% (36/116) with other genotypes (p = 0.075)]. Day 7 lumefantrine concentrations and the number and nature of adverse events were similar between study arms; only one serious adverse event occurred (renal impairment in the no primaquine arm). The artemether–lumefantrine PCR-corrected adequate clinical and parasitological response rate was 100%, with only one re-infection found among the 128 patients who completed 42-day follow-up.ConclusionsSafety, tolerability, CYP2D6 and G6PD variant data from this study support the deployment of the WHO-recommended SLD primaquine without G6PD testing to advance malaria elimination in South African districts with low-intensity residual transmission.Trial registration Pan African Clinical Trial Registry, PACTR201611001859416. Registered 11 November 2016, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=1859