Journal Article > ResearchFull Text
J Infect Dis. 2024 December 16; Volume 230 (Issue 6); e1235-e1244.; DOI:10.1093/infdis/jiae221
Cortes-Azuero O, Lefrancq N, Nikolay B, McKee C, Cappelle J, et al.
J Infect Dis. 2024 December 16; Volume 230 (Issue 6); e1235-e1244.; DOI:10.1093/infdis/jiae221
BACKGROUND
Nipah virus (NiV), a highly lethal virus in humans, circulates in Pteropus bats throughout South and Southeast Asia. Difficulty in obtaining viral genomes from bats means we have a poor understanding of NiV diversity.
METHODS
We develop phylogenetic approaches applied to the most comprehensive collection of genomes to date (N = 257, 175 from bats, 73 from humans) from 6 countries over 22 years (1999–2020). We divide the 4 major NiV sublineages into 15 genetic clusters. Using Approximate Bayesian Computation fit to a spatial signature of viral diversity, we estimate the presence and the average size of genetic clusters per area.
RESULTS
We find that, within any bat roost, there are an average of 2.4 co-circulating genetic clusters, rising to 5.5 clusters at areas of 1500–2000 km2. We estimate that each genetic cluster occupies an average area of 1.3 million km2 (95% confidence interval [CI], .6–2.3 million km2), with 14 clusters in an area of 100 000 km2 (95% CI, 6–24 km2). In the few sites in Bangladesh and Cambodia where genomic surveillance has been concentrated, we estimate that most clusters have been identified, but only approximately 15% of overall NiV diversity has been uncovered.
CONCLUSIONS
Our findings are consistent with entrenched co-circulation of distinct lineages, even within roosts, coupled with slow migration over larger spatial scales.
Conference Material > Poster
Weerasekera C, Gunathilake N, Wimalasiri U, Anpahalan JP, Menike CW, et al.
MSF Scientific Days Asia. 2024 November 8
Conference Material > Video
Weerasekera C
MSF Scientific Days Asia. 2024 October 24
Conference Material > Poster
Ndayisaba R, Colombe S, Van Bortel W, Sinarinzi P, Nzomukunda Y, et al.
MSF Scientific Day International 2024. 2024 May 16; DOI:10.57740/ultcgK
Journal Article > ProtocolFull Text
BMJ Open. 2023 October 28; Volume 13 (Issue 10); e074679.; DOI:10.1136/bmjopen-2023-074679
Kumar R, Dahal P, Singh-Phulgenda S, Siddiqui NA, Munir A, et al.
BMJ Open. 2023 October 28; Volume 13 (Issue 10); e074679.; DOI:10.1136/bmjopen-2023-074679
INTRODUCTION
Visceral leishmaniasis (VL) is a parasitic disease with an estimated 30 000 new cases occurring annually. There is an observed variation in the efficacy of the current first-line therapies across different regions. Such heterogeneity could be a function of host, parasite and drug factors. An individual participant data meta-analysis (IPD-MA) is planned to explore the determinants of treatment outcomes.
METHODS AND ANALYSIS
The Infectious Diseases Data Observatory (IDDO) VL living systematic review (IDDO VL LSR) library is an open-access resource of all published therapeutic studies in VL since 1980. For this current review, the search includes all clinical trials published between 1 January 1980 and 2 May 2021. Studies indexed in the IDDO VL LSR library were screened for eligibility for inclusion in this IPD-MA. Corresponding authors and principal investigators of the studies meeting the eligibility criteria for inclusion were invited to be part of the collaborative IPD-MA. Authors agreeing to participate in this collaborative research were requested to share the IPD using the IDDO VL data platform. The IDDO VL data platform currently holds data sets from clinical trials standardised to a common data format and provides a unique opportunity to identify host, parasite and drug determinants of treatment outcomes. Multivariable regression models will be constructed to identify determinants of therapeutic outcomes using generalised linear mixed-effects models accounting for within-study site clustering.
ETHICS AND DISSEMINATION
This IPD-MA meets the criteria for waiver of ethical review as defined by the Oxford Tropical Research Ethics Committee (OxTREC) granted to IDDO, as the research consists of secondary analysis of existing anonymised data (Exempt granted on 29 March 2023, OxTREC REF: IDDO) Ethics approval was granted by the ICMR-Rajendra Memorial Research Institute of Medical Sciences ethics committee (Letter no: RMRI/EC/30/2022) on 04-07-2022. The results of this IPD-MA will be disseminated at conferences, IDDO website and any peer-reviewed publications. All publications will be open source. Findings of this research will be critically important for the control programmes at regional/global levels, policy makers and groups developing new VL treatments.
Visceral leishmaniasis (VL) is a parasitic disease with an estimated 30 000 new cases occurring annually. There is an observed variation in the efficacy of the current first-line therapies across different regions. Such heterogeneity could be a function of host, parasite and drug factors. An individual participant data meta-analysis (IPD-MA) is planned to explore the determinants of treatment outcomes.
METHODS AND ANALYSIS
The Infectious Diseases Data Observatory (IDDO) VL living systematic review (IDDO VL LSR) library is an open-access resource of all published therapeutic studies in VL since 1980. For this current review, the search includes all clinical trials published between 1 January 1980 and 2 May 2021. Studies indexed in the IDDO VL LSR library were screened for eligibility for inclusion in this IPD-MA. Corresponding authors and principal investigators of the studies meeting the eligibility criteria for inclusion were invited to be part of the collaborative IPD-MA. Authors agreeing to participate in this collaborative research were requested to share the IPD using the IDDO VL data platform. The IDDO VL data platform currently holds data sets from clinical trials standardised to a common data format and provides a unique opportunity to identify host, parasite and drug determinants of treatment outcomes. Multivariable regression models will be constructed to identify determinants of therapeutic outcomes using generalised linear mixed-effects models accounting for within-study site clustering.
ETHICS AND DISSEMINATION
This IPD-MA meets the criteria for waiver of ethical review as defined by the Oxford Tropical Research Ethics Committee (OxTREC) granted to IDDO, as the research consists of secondary analysis of existing anonymised data (Exempt granted on 29 March 2023, OxTREC REF: IDDO) Ethics approval was granted by the ICMR-Rajendra Memorial Research Institute of Medical Sciences ethics committee (Letter no: RMRI/EC/30/2022) on 04-07-2022. The results of this IPD-MA will be disseminated at conferences, IDDO website and any peer-reviewed publications. All publications will be open source. Findings of this research will be critically important for the control programmes at regional/global levels, policy makers and groups developing new VL treatments.
Journal Article > ResearchFull Text
Sci Rep. 2023 October 13; Volume 13 (Issue 1); 17363.; DOI:10.1038/s41598-023-44457-0
Acford-Palmer H, Campos M, Bandibabone JB, N’Do S, Bantuzeko C, et al.
Sci Rep. 2023 October 13; Volume 13 (Issue 1); 17363.; DOI:10.1038/s41598-023-44457-0
Français
Vector control strategies have been successful in reducing the number of malaria cases and deaths globally, but the spread of insecticide resistance represents a significant threat to disease control. Insecticide resistance has been reported across Anopheles (An.) vector populations, including species within the An. funestus group. These mosquitoes are responsible for intense malaria transmission across sub-Saharan Africa, including in the Democratic Republic of the Congo (DRC), a country contributing > 12% of global malaria infections and mortality events. To support the continuous efficacy of vector control strategies, it is essential to monitor insecticide resistance using molecular surveillance tools. In this study, we developed an amplicon sequencing (“Amp-seq”) approach targeting An. funestus, and using multiplex PCR, dual index barcoding, and next-generation sequencing for high throughput and low-cost applications. Using our Amp-seq approach, we screened 80 An. funestus field isolates from the DRC across a panel of nine genes with mutations linked to insecticide resistance (ace-1, CYP6P4, CYP6P9a, GSTe2, vgsc, and rdl) and mosquito speciation (cox-1, mtND5, and ITS2). Amongst the 18 non-synonymous mutations detected, was N485I, in the ace-1 gene associated with carbamate resistance. Overall, our panel represents an extendable and much-needed method for the molecular surveillance of insecticide resistance in An. funestus populations.
Journal Article > ResearchFull Text
Malar J. 2021 December 14; Volume 20 (Issue 1); 464.; DOI:10.1186/s12936-021-04002-8
Bandibabone JB, McLoughlin C, Ndo S, Bantuzeko C, Byabushi V, et al.
Malar J. 2021 December 14; Volume 20 (Issue 1); 464.; DOI:10.1186/s12936-021-04002-8
Français
BACKGROUND
Malaria vector control in the Democratic Republic of the Congo is plagued by several major challenges, including inadequate infrastructure, lack of access to health care systems and preventative measures, and more recently the widespread emergence of insecticide resistance among Anopheles mosquitoes. Across 26 provinces, insecticide resistance has been reported from multiple sentinel sites. However, to date, investigation of molecular resistance mechanisms among Anopheles vector populations in DRC has been more limited.
METHODS
Adult Anopheles gambiae sensu lato (s.l.) and Anopheles funestus s.l. were collected from two sites in Sud-Kivu province and one site in Haut-Uélé province and PCR-screened for the presence of 11 resistance mutations, to provide additional information on frequency of resistance mechanisms in the eastern DRC, and to critically evaluate the utility of these markers for prospective country-wide resistance monitoring.
RESULTS
L1014F-kdr and L1014S-kdr were present in 75.9% and 56.7% of An. gambiae s.l. screened, respectively, with some individuals harbouring both resistant alleles. Across the three study sites, L43F-CYP4J5 allele frequency ranged from 0.42 to 0.52, with evidence for ongoing selection. G119S-ace1 was also identified in all sites but at lower levels. A triple mutant haplotype (comprising the point mutation CYP6P4-I236M, the insertion of a partial Zanzibar-like transposable element and duplication of CYP6AA1) was present at high frequencies. In An. funestus s.l. cis-regulatory polymorphisms in CYP6P9a and CYP6P9b were detected, with allele frequencies ranging from 0.82 to 0.98 and 0.65 to 0.83, respectively.
CONCLUSIONS
This study screened the most up-to-date panel of DNA-based resistance markers in An. gambiae s.l. and An. funestus s.l. from the eastern DRC, where resistance data is lacking. Several new candidate markers (CYP4J5, G119S-ace1, the triple mutant, CYP6P9a and CYP6P9b) were identified, which are diagnostic of resistance to major insecticide classes, and warrant future, larger-scale monitoring in the DRC to inform vector control decisions by the National Malaria Control Programme.
Malaria vector control in the Democratic Republic of the Congo is plagued by several major challenges, including inadequate infrastructure, lack of access to health care systems and preventative measures, and more recently the widespread emergence of insecticide resistance among Anopheles mosquitoes. Across 26 provinces, insecticide resistance has been reported from multiple sentinel sites. However, to date, investigation of molecular resistance mechanisms among Anopheles vector populations in DRC has been more limited.
METHODS
Adult Anopheles gambiae sensu lato (s.l.) and Anopheles funestus s.l. were collected from two sites in Sud-Kivu province and one site in Haut-Uélé province and PCR-screened for the presence of 11 resistance mutations, to provide additional information on frequency of resistance mechanisms in the eastern DRC, and to critically evaluate the utility of these markers for prospective country-wide resistance monitoring.
RESULTS
L1014F-kdr and L1014S-kdr were present in 75.9% and 56.7% of An. gambiae s.l. screened, respectively, with some individuals harbouring both resistant alleles. Across the three study sites, L43F-CYP4J5 allele frequency ranged from 0.42 to 0.52, with evidence for ongoing selection. G119S-ace1 was also identified in all sites but at lower levels. A triple mutant haplotype (comprising the point mutation CYP6P4-I236M, the insertion of a partial Zanzibar-like transposable element and duplication of CYP6AA1) was present at high frequencies. In An. funestus s.l. cis-regulatory polymorphisms in CYP6P9a and CYP6P9b were detected, with allele frequencies ranging from 0.82 to 0.98 and 0.65 to 0.83, respectively.
CONCLUSIONS
This study screened the most up-to-date panel of DNA-based resistance markers in An. gambiae s.l. and An. funestus s.l. from the eastern DRC, where resistance data is lacking. Several new candidate markers (CYP4J5, G119S-ace1, the triple mutant, CYP6P9a and CYP6P9b) were identified, which are diagnostic of resistance to major insecticide classes, and warrant future, larger-scale monitoring in the DRC to inform vector control decisions by the National Malaria Control Programme.
Journal Article > ResearchFull Text
Trop Med Int Health. 2008 December 1; Volume 13 (Issue 12); 1479-1487.; DOI:10.1111/j.1365-3156.2008.02164.x
Protopopoff N, Verhaeghen K, Van Bortel W, Roelants P, Marcotty T, et al.
Trop Med Int Health. 2008 December 1; Volume 13 (Issue 12); 1479-1487.; DOI:10.1111/j.1365-3156.2008.02164.x
Français
OBJECTIVES AND METHODS: In Burundi, the occurrence of the knock down resistance (kdr) mutation in Anopheles gambiae sensu lato (s.l.) was determined for six consecutive years within the framework of a vector control programme. Findings were also linked with the insecticide resistance status observed with bioassay in An. gambiae s.l. and An. funestus.
RESULTS: The proportion of An. gambiae s.l. carrying the East Leu-Ser kdr mutation was 1% before the spraying intervention in 2002; by 2007 it was 86% in sprayed valleys and 67% in untreated valleys. Multivariate analysis showed that increased risk of carrying the kdr mutation is associated with spraying interventions, location and time. In bioassays conducted between 2005 and 2007 at five sites, An. funestus was susceptible to permethrin, deltamethrin and DDT. Anopheles gambiae s.l. remained susceptible or tolerant to deltamethrin and resistant to DDT and permethrin, but only when kdr allele carriers reached 90% of the population.
CONCLUSIONS: The cross-resistance against DDT and permethrin in Karuzi suggests a possible kdr resistance mechanism. Nevertheless, the homozygous resistant genotype alone does not entirely explain the bioassay results, and other mechanisms conferring resistance cannot be ruled out. After exposure to all three insecticides, homozygote individuals for the kdr allele dominate among the surviving An. gambiae s.l. This confirms the potential selection pressure of pyrethroids on kdr mutation. However, the high occurrence of the kdr mutation, even at sites far from the sprayed areas, suggests a selection pressure other than that exerted by the vector control programme.
RESULTS: The proportion of An. gambiae s.l. carrying the East Leu-Ser kdr mutation was 1% before the spraying intervention in 2002; by 2007 it was 86% in sprayed valleys and 67% in untreated valleys. Multivariate analysis showed that increased risk of carrying the kdr mutation is associated with spraying interventions, location and time. In bioassays conducted between 2005 and 2007 at five sites, An. funestus was susceptible to permethrin, deltamethrin and DDT. Anopheles gambiae s.l. remained susceptible or tolerant to deltamethrin and resistant to DDT and permethrin, but only when kdr allele carriers reached 90% of the population.
CONCLUSIONS: The cross-resistance against DDT and permethrin in Karuzi suggests a possible kdr resistance mechanism. Nevertheless, the homozygous resistant genotype alone does not entirely explain the bioassay results, and other mechanisms conferring resistance cannot be ruled out. After exposure to all three insecticides, homozygote individuals for the kdr allele dominate among the surviving An. gambiae s.l. This confirms the potential selection pressure of pyrethroids on kdr mutation. However, the high occurrence of the kdr mutation, even at sites far from the sprayed areas, suggests a selection pressure other than that exerted by the vector control programme.
Journal Article > ResearchFull Text
Malar J. 2020 November 23; Volume 19 (Issue 1); 425.; DOI:10.1186/s12936-020-03497-x
Loonen JACM, Dery DB, Musaka BZ, Bandibabone JB, Bousema T, et al.
Malar J. 2020 November 23; Volume 19 (Issue 1); 425.; DOI:10.1186/s12936-020-03497-x
Français
BACKGROUND
Malaria remains a major public health concern in the Democratic Republic of the Congo (DRC) and its control is affected by recurrent conflicts. Médecins Sans Frontières (MSF) initiated several studies to better understand the unprecedented incidence of malaria to effectively target and implement interventions in emergency settings. The current study evaluated the main vector species involved in malaria transmission and their resistance to insecticides, with the aim to propose the most effective tools and strategies for control of local malaria vectors.
METHODS
This study was performed in 52 households in Shamwana (Katanga, 2014), 168 households in Baraka (South Kivu, 2015) and 269 households in Kashuga (North Kivu, 2017). Anopheles vectors were collected and subjected to standardized Word Health Organization (WHO) and Center for Disease Control (CDC) insecticide susceptibility bioassays. Mosquito species determination was done using PCR and Plasmodium falciparum infection in mosquitoes was assessed by ELISA targeting circumsporozoite protein.
RESULTS
Of 3517 Anopheles spp. mosquitoes collected, Anopheles gambiae sensu lato (s.l.) (29.6%) and Anopheles funestus (69.1%) were the main malaria vectors. Plasmodium falciparum infection rates for An. gambiae s.l. were 1.0, 2.1 and 13.9% for Shamwana, Baraka and Kashuga, respectively. Anopheles funestus showed positivity rates of 1.6% in Shamwana and 4.4% in Baraka. No An. funestus were collected in Kashuga. Insecticide susceptibility tests showed resistance development towards pyrethroids in all locations. Exposure to bendiocarb, malathion and pirimiphos-methyl still resulted in high mosquito mortality.
CONCLUSIONS
This is one of only few studies from these conflict areas in DRC to report insecticide resistance in local malaria vectors. The data suggest that current malaria prevention methods in these populations are only partially effective, and require additional tools and strategies. Importantly, the results triggered MSF to consider the selection of a new insecticide for indoor residual spraying (IRS) and a new long-lasting insecticide-treated net (LLIN). The reinforcement of correct usage of LLINs and the introduction of targeted larviciding were also included as additional vector control tools as a result of the studies.
Malaria remains a major public health concern in the Democratic Republic of the Congo (DRC) and its control is affected by recurrent conflicts. Médecins Sans Frontières (MSF) initiated several studies to better understand the unprecedented incidence of malaria to effectively target and implement interventions in emergency settings. The current study evaluated the main vector species involved in malaria transmission and their resistance to insecticides, with the aim to propose the most effective tools and strategies for control of local malaria vectors.
METHODS
This study was performed in 52 households in Shamwana (Katanga, 2014), 168 households in Baraka (South Kivu, 2015) and 269 households in Kashuga (North Kivu, 2017). Anopheles vectors were collected and subjected to standardized Word Health Organization (WHO) and Center for Disease Control (CDC) insecticide susceptibility bioassays. Mosquito species determination was done using PCR and Plasmodium falciparum infection in mosquitoes was assessed by ELISA targeting circumsporozoite protein.
RESULTS
Of 3517 Anopheles spp. mosquitoes collected, Anopheles gambiae sensu lato (s.l.) (29.6%) and Anopheles funestus (69.1%) were the main malaria vectors. Plasmodium falciparum infection rates for An. gambiae s.l. were 1.0, 2.1 and 13.9% for Shamwana, Baraka and Kashuga, respectively. Anopheles funestus showed positivity rates of 1.6% in Shamwana and 4.4% in Baraka. No An. funestus were collected in Kashuga. Insecticide susceptibility tests showed resistance development towards pyrethroids in all locations. Exposure to bendiocarb, malathion and pirimiphos-methyl still resulted in high mosquito mortality.
CONCLUSIONS
This is one of only few studies from these conflict areas in DRC to report insecticide resistance in local malaria vectors. The data suggest that current malaria prevention methods in these populations are only partially effective, and require additional tools and strategies. Importantly, the results triggered MSF to consider the selection of a new insecticide for indoor residual spraying (IRS) and a new long-lasting insecticide-treated net (LLIN). The reinforcement of correct usage of LLINs and the introduction of targeted larviciding were also included as additional vector control tools as a result of the studies.
Journal Article > Short ReportFull Text
MMWR Morb Mortal Wkly Rep. 2007 February 2; Volume 56 (Issue 4); 73-76.
Nguku PM, Sharif S, Omar A, Nzioka C, Muthoka P, et al.
MMWR Morb Mortal Wkly Rep. 2007 February 2; Volume 56 (Issue 4); 73-76.
In mid-December 2006, several unexplained fatalities associated with fever and generalized bleeding were reported to the Kenya Ministry of Health (KMOH) from Garissa District in North Eastern Province (NEP). By December 20, a total of 11 deaths had been reported. Of serum samples collected from the first 19 patients, Rift Valley fever (RVF) virus RNA or immunoglobulin M (IgM) antibodies against RVF virus were found in samples from 10 patients; all serum specimens were negative for yellow fever, Ebola, Crimean-Congo hemorrhagic fever, and dengue viruses. The outbreak was confirmed by isolation of RVF virus from six of the specimens. Humans can be infected with RVF virus from bites of mosquitoes or other arthropod vectors that have fed on animals infected with RVF virus, or through contact with viremic animals, particularly livestock. Reports of livestock deaths and unexplained animal abortions in NEP provided further evidence of an RVF outbreak. On December 20, an investigation was launched by KMOH, the Kenya Field Epidemiology and Laboratory Training Program (FELTP), the Kenya Medical Research Institute (KEMRI), the Walter Reed Project of the U.S. Army Medical Research Unit, CDC-Kenya's Global Disease Detection Center, and other partners, including the World Health Organization (WHO) and Médecins Sans Frontières (MSF). This report describes the findings from that initial investigation and the control measures taken in response to the RVF outbreak, which spread to multiple additional provinces and districts, resulting in 404 cases with 118 deaths as of January 25, 2007.