Urban Malaria Research Articles

The genome trilogy of Anopheles stephensi, an urban malaria vector, reveals structure of a locus associated with adaptation to environmental heterogeneity

Anopheles stephensi is the most menacing malaria vector to watch for in newly urbanising parts of the world. Its fitness is reported to be a direct consequence of the vector adapting to laying eggs in over-head water tanks with street-side water puddles polluted by oil and sewage. Large frequent inversions in the genome of malaria vectors are implicated in adaptation. We report the genome assembly of a strain of An. stephensi of the type-form, collected from a construction site from Chennai (IndCh) in 2016. The genome reported here with a L50 of 4, completes the trilogy of high-resolution genomes of strains with respect to a 16.5 Mbp 2Rb genotype in An. stephensi known to be associated with adaptation to environmental heterogeneity. Unlike the reported genomes of two other strains, STE2 (2R+b/2Rb) and UCI (2Rb/2Rb), IndCh is found to be homozygous for the standard form (2R+b/2R+b). Comparative genome analysis revealed base-level details of the breakpoints and allowed extraction of 22,650 segregating SNPs for typing this inversion in populations. Whole genome sequencing of 82 individual mosquitoes from diverse geographical locations reveal that one third of both wild and laboratory populations maintain the heterozygous genotype of 2Rb. The large number of SNPs can be tailored to 1740 exonic SNPs enabling genotyping directly from transcriptome sequencing. The genome trilogy approach accelerated the study of fine structure and typing of an important inversion in An. stephensi, putting the genome resources for this understudied species on par with the extensively studied malaria vector, Anopheles gambiae. We argue that the IndCh genome is relevant for field translation work compared to those reported earlier by showing that individuals from diverse geographical locations cluster with IndCh, pointing to significant convergence resulting from travel and commerce between cities, perhaps, contributing to the survival of the fittest strain.

Magnitude of urban malaria and its associated risk factors: the case of Batu town, Oromia Regional State, Ethiopia.

ObjectiveThis study aimed to assess the magnitude of malaria and its associated risk factors in urban, Batu town, Oromia Regional State, Ethiopia.MethodsThis health-facility based prospective cross-sectional study enrolled 356 febrile malaria patients to assess risk factors associated with malaria infection.ResultsAn overall positivity rate of 17.13% (61/356) for malaria infection was observed. Among the malaria-positive patients, 50.8% (31/61) of them were positive for Plasmodium vivax, 45.90% (28/61) were positive for Plasmodium falciparum, and 3.3% (2/61) had mixed infections of P. falciparum and P. vivax. Logistic regression analysis revealed that individuals who possessed insecticide-treated net (Odds ratio [OR] = 0.38, 95% confidence interval [CI] [0.194, 0.743]) and whose houses were sprayed with insecticides (OR = 0.18, 95% CI [0.097, 0.34]) were significantly less likely to have a malaria infection. Individuals living closer to stagnant water had a significantly greater chance of malaria infection than those who lived a distance from stagnant water (OR = 0.34, 95% CI [0.19, 0.59]).ConclusionThe present study revealed that malaria remains a public health problem in the urban area of Batu town, which suggests that the same might be true for other urban areas in the country.

The neglected role of relative humidity in the interannual variability of urban malaria in Indian cities

The rapid pace of urbanization makes it imperative that we better understand the influence of climate forcing on urban malaria transmission. Despite extensive study of temperature effects in vector-borne infections in general, consideration of relative humidity remains limited. With process-based dynamical models informed by almost two decades of monthly surveillance data, we address the role of relative humidity in the interannual variability of epidemic malaria in two semi-arid cities of India. We show a strong and significant effect of humidity during the pre-transmission season on malaria burden in coastal Surat and more arid inland Ahmedabad. Simulations of the climate-driven transmission model with the MLE (Maximum Likelihood Estimates) of the parameters retrospectively capture the observed variability of disease incidence, and also prospectively predict that of ‘out-of-fit’ cases in more recent years, with high accuracy. Our findings indicate that relative humidity is a critical factor in the spread of urban malaria and potentially other vector-borne epidemics, and that climate change and lack of hydrological planning in cities might jeopardize malaria elimination efforts.

Drawings as tools to (re)imagine space in interdisciplinary global health research.

Understanding the role of space in infectious diseases' dynamics in urban contexts is key to developing effective mitigation strategies. Urbanism, a discipline that both studies and acts upon the city, commonly uses drawings to analyze spatial patterns and their variables. This paper revisits drawings as analytical and integrative tools for interdisciplinary research. We introduce the use of drawings in two interdisciplinary projects conducted in the field of global public health: first, a study about the heterogeneous burden of tuberculosis and COVID-19 in Lima, Peru, and second, a study about urban malaria in Jimma, Ethiopia. In both cases, drawings such as maps, plans, and sections were used to analyze spatial factors present in the urban context at different scales: from the scale of the territory, the city, and the district, to the neighborhood and the household. We discuss the methodological approaches taken in both cases, considering the nature of the diseases being investigated as well as the natural and social context in which the studies took place. We contend that the use of drawings helps to reimagine space in public health research by adding a multidimensional perspective to spatial variables and contexts. The processes and products of drawing can help to (a) identify systemic relations within the spatial context, (b) facilitate integration of quantitative and qualitative data, and (c) guide the formulation of policy recommendations, informing public and urban health planning.

Field evaluation of biosurfactants, surfactin and di-rhamnolipid produced by Bacillus subtilis subsp. subtilis (VCRC B471) and Pseudomonas fluorescens (VCRC B426) against immature stages of the urban malaria vector Anopheles stephensi.

Bacillus subtilis subsp. subtilis (VCRC B471) and Pseudomonas fluorescens (B426) produce mosquitocidal biosurfactant, surfactin and di-rhamnolipid. The objective of the study was to carry out a small-scale field evaluation of the two biosurfactants to determine the efficacy, application dosage, residual activity and frequency of application against Anopheles stephensi immatures in selected sites in Goa, India. Surfactin (VCRC B471) and di-rhamnolipid (VCRC B426) were formulated as aqueous suspensions (5% AS), and were applied at the dosages of 34, 51 and 68 mL/m2 and 27, 41 and 54 mL/m2 respectively. Two experiments were carried out with the two formulations. Surfactin (VCRC B471) formulation was effective at all the dosages and there was sustained reduction (>80%) in immature density in the treated sites up to 18 days in experiment 1 and up to 15 days in experiment 2. No pupae were found in the treated sites throughout the study. Di-rhamnolipid (VCRC B426) formulation was also found to reduce the immature density in the treated sites up to 14 days in experiment 1 and up to 15 days in experiment 2. For VCRC B471, the optimum application dosage determined was 51 mL/m2 and for VCRC B426, 27mL/m2. The formulations are to be applied fortnightly for effective control of Anopheles. The application dosage determined in the present study can be used for large scale field evaluation to assess their suitability for use in public health programmes for the control of Anopheles mosquitoes vectoring malaria.

Modernisasi Kota dan Bencana Wabah Malaria di Cirebon Tahun 1930-an

This article aimed to explain the process of urban modernization and malaria outbreak in the colonial era. The emphasis on modernization is based on several documents from the Nederlandsche Indies government regarding the formation of cities in Java which prioritized infrastructure development for economic that so triggered the malaria outbreak, especially in coastal areas and plantations. This modernization program based on economic industrialization has influenced the economic people, workers, traders, employees, and healers. In the process of modernization, the emergence of the malaria outbreak spreads to the people. Therefore, the focus of this research analysis is on the modernization process and malaria outbreak in Cirebon in the colonial era. It is important to note that modernization does not does not always produce cultural products that have a positive impact. In addition, it is also for the assumption that the malaria outbreak is an environmental problem due to ignorant public health problem.

Does the roof type of a house influence the presence of adult Anopheles stephensi, urban malaria vector? - evidence from a few slum settings in Chennai, India.

In an urban setting, it is a difficult task to collect adult Anopheles stephensi, unlike the immature stages, due to various reasons. A longitudinal study was undertaken from January 2016 to April 2017, with CDC light traps to collect adult Anopheles stephensi and other mosquito species in houses located in a few slums of Chennai, India. A total of 203 trap collections were made indoors from human dwellings having different roof types, as well as outdoors. Three to four trap collections were made at night (18:00 to 06:00 h) once a week. Overall, Culex quinquefasciatus (64%) was the predominant mosquito species captured, followed by An. stephensi (24%). In 98 of the 203 trap collections (48.3%), at least one female An. stephensi was trapped. In all, 224 female An. stephensi were trapped, of which the majority were collected during monsoon and winter seasons. Compared to outdoors, 10% more An. stephensi, the majority of them unfed, were collected indoors, with relatively more contribution coming from asbestos-roofed houses (71.4%), followed by thatched-roof houses (47.3%). Overall, 2.2% positivity for Plasmodium vivax was detected in An. stephensi through Circumsporozoite-ELISA. Binary logistic regression model indicated that season (winter and monsoon), asbestos-roofed dwelling, lesser number of rooms in a house, and more members in a family were significant predictor variables for the odds of trapping an An. stephensi. The study brought out significant factors associated with the presence of An. stephensi in urban slums setting in Chennai, where malaria is declining. The findings would help in devising targeted, effective vector control interventions for malaria elimination in urban settings.

The Effect of Socioeconomic Factors and Indoor Residual Spraying on Malaria in Mangaluru, India: A Case-Control Study.

India faces 0.5 million malaria cases annually, including half of all Plasmodium vivax malaria cases worldwide. This case–control study assessed socioeconomic determinants of urban malaria in coastal Mangaluru, Karnataka, southwestern India. Between June and December 2015, we recruited 859 malaria patients presenting at the governmental Wenlock Hospital and 2190 asymptomatic community controls. We assessed clinical, parasitological, and socioeconomic data. Among patients, p. vivax mono-infection (70.1%) predominated. Most patients were male (93%), adult (median, 27 years), had no or low-level education (70.3%), and 57.1% were daily labourers or construction workers. In controls (59.3% male; median age, 32 years; no/low-level education, 54.5%; daily labourers/construction workers, 41.3%), 4.1% showed asymptomatic Plasmodium infection. The odds of malaria was reduced among those who had completed 10th school grade (aOR, 0.3; 95% CI, 0.26–0.42), lived in a building with a tiled roof (aOR, 0.71; 95% CI, 0.53–0.95), and reported recent indoor residual spraying (aOR, 0.02; 95% CI, 0.01–0.04). In contrast, migrant status was a risk factor for malaria (aOR, 2.43; 95% CI, 1.60–3.67). Malaria in Mangaluru is influenced by education, housing condition, and migration. Indoor residual spraying greatly contributes to reducing malaria in this community and should be promoted, especially among its marginalised members.

Invasive Malaria Vector Anopheles stephensi Mosquitoes in Sudan, 2016-2018.

Anopheles stephensi mosquitoes are urban malaria vectors in Asia that have recently invaded the Horn of Africa. We detected emergence of An. stephensi mosquitoes in 2 noncontiguous states of eastern Sudan. Results of mitochondrial DNA sequencing suggest the possibility of distinct invasions, potentially from a neighboring country.

Cohort profile: the Mâncio Lima cohort study of urban malaria in Amazonian Brazil

PurposeThis population-based open cohort study aims to investigate biological and sociodemographic drivers of malaria transmission in the main urban hotspot of Amazonian Brazil.ParticipantsNearly 20% of the households in the northwestern...

Production of Urban Space and the occurrence of malaria in the Brazilian Amazon: the Porto Velho case.

Due to intense ongoing urbanization in the Amazon, the urban pattern of malaria may be changing, both in its spatial distribution and epidemiological profile. The purpose of this paper is to analyze how the process of production of urban space in Porto Velho, the capital of the state of Rondonia, Brazil has contributed to the occurrence and maintenance of urban malaria. Using data collected from the Malaria Epidemiological Surveillance System (SIVEP-Malaria), we calculated malaria indices for the districts of Porto Velho from 2005 to 2018. We also developed two typologies for classifying urban space based on functional characteristics and features of the landscape. While the former considers characteristics of urban space in Porto Velho, the latter is based on suitability for malaria vectors. We found that the annual parasite index declined in Porto Velho during the study period. However, changes in the index were not uniform across the districts of the city. Periurban areas showed no decline in the index, which we attribute to these areas' high vegetation density and hydrological characteristics.

Optimization of Plasmodium vivax sporozoite production from Anopheles stephensi in South West India

BackgroundEfforts to study the biology of Plasmodium vivax liver stages, particularly the latent hypnozoites, have been hampered by the limited availability of P. vivax sporozoites. Anopheles stephensi is a major urban malaria vector in Goa and elsewhere in South Asia. Using P. vivax patient blood samples, a series of standard membrane-feeding experiments were performed with An. stephensi under the US NIH International Center of Excellence for Malaria Research (ICEMR) for Malaria Evolution in South Asia (MESA). The goal was to understand the dynamics of parasite development in mosquitoes as well as the production of P. vivax sporozoites. To obtain a robust supply of P. vivax sporozoites, mosquito-rearing and mosquito membrane-feeding techniques were optimized, which are described here.MethodsMembrane-feeding experiments were conducted using both wild and laboratory-colonized An. stephensi mosquitoes and patient-derived P. vivax collected at the Goa Medical College and Hospital. Parasite development to midgut oocysts and salivary gland sporozoites was assessed on days 7 and 14 post-feeding, respectively. The optimal conditions for mosquito rearing and feeding were evaluated to produce high-quality mosquitoes and to yield a high sporozoite rate, respectively.ResultsLaboratory-colonized mosquitoes could be starved for a shorter time before successful blood feeding compared with wild-caught mosquitoes. Optimizing the mosquito-rearing methods significantly increased mosquito survival. For mosquito feeding, replacing patient plasma with naïve serum increased sporozoite production > two-fold. With these changes, the sporozoite infection rate was high (> 85%) and resulted in an average of ~ 22,000 sporozoites per mosquito. Some mosquitoes reached up to 73,000 sporozoites. Sporozoite production could not be predicted from gametocyte density but could be predicted by measuring oocyst infection and oocyst load.ConclusionsOptimized conditions for the production of high-quality P. vivax sporozoite-infected An. stephensi were established at a field site in South West India. This report describes techniques for producing a ready resource of P. vivax sporozoites. The improved protocols can help in future research on the biology of P. vivax liver stages, including hypnozoites, in India, as well as the development of anti-relapse interventions for vivax malaria.

Immunological, haematological, and clinical attributes of rural and urban malaria: a case-control study in Ghana.

To compare clinical presentations, haematological and immunological parameters in urban and rural malaria patients. Clinically suspected malaria patients, resident in either rural or urban communities, were selected from seven health facilities in the Greater Accra region of Ghana. For each suspected malaria patient, parasites were detected microscopically and quantified subsequently. In each study site, an equal number of cases and age-matched controls were selected. In both cases and controls, clinical presentations, nutritional status, haematological, and immunological parameters were profiled. A total of 149 malaria patients and 149 nonmalaria controls were selected. Compared to rural dwellers with malaria, parasitaemia was significantly higher in both males and females and in the various age groups in urban dwellers with malaria. Additionally, mean lymphocytes, haemoglobin, haematocrit, mean cell haemoglobin, platelets, and mean platelet volume levels were significantly lower in urban dwellers with malaria. However, TNF-α, IL-6, and IL-12 levels in urban dwellers with malaria were significantly higher, while IL-10, CD4+, CD3+, CD8+ T-cells levels and CD4+/ CD3+ ratio were significantly lower in urban dwellers with malaria. Furthermore, chills, diarrhoea, fever, and pallor were significantly associated with urban dwellers with malaria. This study concluded that urban dwellers are more prone to severe malaria while rural dwellers tend to have more measured immune response against malaria infection, and therefore experienced better controlled inflammatory processes associated with mild form of the disease.

Hidden genomic features of an invasive malaria vector, Anopheles stephensi, revealed by a chromosome-level genome assembly

BackgroundThe mosquito Anopheles stephensi is a vector of urban malaria in Asia that recently invaded Africa. Studying the genetic basis of vectorial capacity and engineering genetic interventions are both impeded by limitations of a vector’s genome assembly. The existing assemblies of An. stephensi are draft-quality and contain thousands of sequence gaps, potentially missing genetic elements important for its biology and evolution.ResultsTo access previously intractable genomic regions, we generated a reference-grade genome assembly and full transcript annotations that achieve a new standard for reference genomes of disease vectors. Here, we report novel species-specific transposable element (TE) families and insertions in functional genetic elements, demonstrating the widespread role of TEs in genome evolution and phenotypic variation. We discovered 29 previously hidden members of insecticide resistance genes, uncovering new candidate genetic elements for the widespread insecticide resistance observed in An. stephensi. We identified 2.4 Mb of the Y chromosome and seven new male-linked gene candidates, representing the most extensive coverage of the Y chromosome in any mosquito. By tracking full-length mRNA for > 15 days following blood feeding, we discover distinct roles of previously uncharacterized genes in blood metabolism and female reproduction. The Y-linked heterochromatin landscape reveals extensive accumulation of long-terminal repeat retrotransposons throughout the evolution and degeneration of this chromosome. Finally, we identify a novel Y-linked putative transcription factor that is expressed constitutively throughout male development and adulthood, suggesting an important role.ConclusionCollectively, these results and resources underscore the significance of previously hidden genomic elements in the biology of malaria mosquitoes and will accelerate the development of genetic control strategies of malaria transmission.

Combined Epidemiologic and Entomologic Survey to Detect Urban Malaria Transmission, Guinea, 2018.

Malaria incidence is generally lower in cities than rural areas. However, reported urban malaria incidence may not accurately reflect the level of ongoing transmission, which has potentially large implications for prevention efforts. To guide mosquito net distribution, we assessed the extent of malaria transmission in Conakry, Guinea, in 2018. We found evidence of active malaria transmission.

Operational Evaluation of the Effectiveness of Long-lasting Insecticidal Nets on Human-Vector Contact in an African Urban Malaria Context

BackgroundMalaria is still a major public health concern in Côte d’Ivoire despite mass distribution of long-lasting insecticidal nets (LLINs) as a key preventive strategy. This study intended to evaluate the operational effectiveness of LLINs on the level of human-vector contact using 1 antibody-based biomarker of exposure to Anopheles in urban areas.MethodsThis cross-sectional study collected socio-demographic data and use of LLINs from 9 neighborhoods in the city of Bouaké (Côte d’Ivoire). Dry blood spots performed in children aged >6 months and adults were used to evaluate immunoglobulin G (IgG) responses to the Anopheles gSG6-P1 salivary peptide.ResultsIgG response levels to the salivary peptide were significantly lower in individuals who declared having “always” (n = 270) slept under an LLIN compared with those who had “often” (n = 2087) and “never” (n = 88) slept under an LLIN (P < .0001). IgG response levels to gSG6-P1 between those who declared having “always” and “not always” slept under an LLIN varied according to neighborhood, socio-professional category, and age group.ConclusionsThe human IgG level to this gSG6-P1 salivary peptide could be a useful tool to evaluate the actual effectiveness of LLINs and help design behavioral change interventions that are crucial for sustaining universal coverage.

Quantifying Climatic and Socio-Economic Influences on Urban Malaria in Surat, India: A Modelling Study

Background: Cities are becoming increasingly important habitats for mosquito-borne infections. The pronounced heterogeneity of urban landscapes challenges our understanding of the spatio-temporal dynamics of these diseases, and of the influence of climate and socio-economic factors at different spatial scales. Here, we quantify this joint influence on malaria risk by taking advantage of an extensive dataset in both space and time for reported Plasmodium falciparum cases in the city of Surat, Northwest India. Methods: We analyzed 10 years of monthly falciparum cases resolved at three nested spatial resolutions (for 7 zones, 32 units and 478 workers unit’s subdivisions, respectively). With a Bayesian hierarchical mixed model that incorporates effects of population density, poverty, humidity and temperature, we investigate the main drivers of spatio-temporal malaria risk at the intermediate scale of districts. The significance of covariates and the model fit is then examined at lower and higher resolutions. Findings: The spatial variation of urban malaria cases is strongly stationary in time, whereby locations exhibiting high and low yearly cases remain largely consistent across years. Local socio-economic variation can be summarized with two main principal components, representing poverty and population density respectively. The model that incorporates these two factors together with local temperature and global relative humidity, best explains monthly malaria patterns at the intermediate resolution. The effects of local temperature and population density remain significant at the finest spatial scale. We further identify the specific areas where such increased resolution improves model fit. Interpretation: Malaria risk patterns within the city are largely driven by fixed spatial structures, highlighting the key role of local climate conditions and social inequality. As a result, malaria elimination efforts in the Indian subcontinent can benefit from identifying, predicting and targeting disease hotspots within cities. Spatio-temporal statistical models for the mesoscale of administrative units can inform control efforts, and be complemented with bespoke plans in the identified areas where finer scale data could be of value. Funding Statement: MP was supported by NIH (grant number 1R01AI153444). RL was supported by a Royal Society Dorothy Hodgkin Fellowship. We acknowledge the Gardner High Performance Computing (HPC) cluster from the Center for Research Informatics of the University of Chicago for computational resources. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: No ethical approval was required for this research since all the epidemiological data was at the population and not the individual level, at spatial resolutions that encompass subpopulations of at least 10000 individuals. The survey data was anonymized and provided to us by TARU leading edge.

Can we use local climate zones for predicting malaria prevalence across sub-Saharan African cities?

Malaria burden is increasing in sub-Saharan cities because of rapid and uncontrolled urbanization. Yet very few studies have studied the interactions between urban environments and malaria. Additionally, no standardized urban land-use/land-cover has been defined for urban malaria studies. Here, we demonstrate the potential of local climate zones (LCZs) for modeling malaria prevalence rate (PfPR) and studying malaria prevalence in urban settings across nine sub-Saharan African cities. Using a random forest classification algorithm over a set of 365 malaria surveys we: (i) identify a suitable set of covariates derived from open-source earth observations; and (ii) depict the best buffer size at which to aggregate them for modeling PfPR.Our results demonstrate that geographical models can learn from LCZ over a set of cities and be transferred over a city of choice that has few or no malaria surveys. In particular, we find that urban areas systematically have lower PfPR (5%–30%) than rural areas (15%–40%). The PfPR urban-to-rural gradient is dependent on the climatic environment in which the city is located. Further, LCZs show that more open urban environments located close to wetlands have higher PfPR. Informal settlements—represented by the LCZ 7 (lightweight lowrise)—have higher malaria prevalence than other densely built-up residential areas with a mean prevalence of 11.11%. Overall, we suggest the applicability of LCZs for more exploratory modeling in urban malaria studies.

Human mobility and urban malaria risk in the main transmission hotspot of Amazonian Brazil.

Malaria in the Amazon is often perceived as an exclusively rural disease, but transmission has been increasingly documented within and near urban centers. Here we explore patterns and causes of urban-to-rural mobility, which places travelers at risk of malaria in Mâncio Lima, the main malaria hotspot in northwestern Brazil. We also analyze rural-to-urban mobility caused by malaria treatment seeking, which poses an additional risk of infection to urban residents. We show that the rural localities most frequently visited by urban residents–typically farming settlements in the vicinity of the town–are those with the most intense malaria transmission and also the most frequent source localities of imported malaria cases diagnosed in the town. The most mobile urban residents are typically poor males 16 to 60-years old from multi-sited households who lack a formal job. Highly mobile residents represent a priority target for more intensive and effective malaria control interventions, that cannot be readily delivered to the entire community, in this and similar urbanized endemic settings across the Amazon.

Disregarding reservoirs of disease vectors: A surveillance paradox in Africa.

Disregarding reservoirs of disease vectors: A surveillance paradox in Africa.