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1.
PLoS Negl Trop Dis ; 17(11): e0011802, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38011275

ABSTRACT

BACKGROUND: Significant progress has been made towards African sleeping sickness elimination in the last decade. Indeed, the World Health Organization (WHO) global goal of eliminating the chronic form of the disease as a public health problem was achieved in 2020 (i.e., < 2,000 new cases per year). Vector control has played an important role in achieving this goal. In this study, we evaluated the impact of the insecticide impregnated Tiny Targets on tsetse fly densities and their infection rates with Trypanosoma spp in the Campo sleeping sickness focus of South Cameroon. METHODS: The study site was divided into two areas: (i) the south-west experimental area, which included vector control, and (ii) the eastern part as the non-intervention area. After compiling the baseline entomological data (tsetse densities and trypanosome infection rates), around 2000 Tiny Targets were deployed in the South-West area and replaced every six months for two years. Post-intervention surveys were conducted every six months to determine tsetse densities and levels of trypanosome infections with PCR-based methods. RESULTS: Following the intervention, tsetse mean catches decreased by 61% after six months, and up to 73% after twelve months (pre-intervention: 2.48 flies/trap/day, 95%CI [1.92-3.14]; 12-months post-intervention: 0.66 tsetse/trap/day, 95%CI [0.42-0.94]). This decrease was not sustained after 18 months, and the mean catch doubled compared to that after 12 months. After 24 months, the mean catches still increased by 17% (18 months: 1.45 tsetse/trap/day, 95%CI [1.07-1.90] and 24 months: 1.71 tsetse/trap/day, 95%CI [1.27-2.24]). In the non-intervention area, a variation in tsetse catches was observed during the two years, with a general increase from 2.43 [0.73-5.77] to 3.64 [1.47-7.70] tsetse/trap/day. In addition, trypanosome infection rates dropped by 75% in both areas (P-value < 0.001) from 21.20% to 5.06% and from 13.14% to 3.45% in intervention and control areas respectively. CONCLUSION: Tiny targets have proven useful in reducing tsetse population densities and trypanosome infection rates, providing evidence for the integration of this tool in current strategies towards trypanosomiasis elimination in Campo. The non-sustained decrease of tsetse densities after one year may indicate reinvasions from neighbouring breeding sites or that the intervention area was not large enough. Our results show the need to scale up by accessing difficult breeding sites and extend the tiny targets to the whole transborder focus.


Subject(s)
Trypanosoma , Trypanosomiasis, African , Tsetse Flies , Animals , Trypanosomiasis, African/epidemiology , Trypanosomiasis, African/prevention & control , Cameroon/epidemiology
2.
Int J Infect Dis ; 137: 114-117, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37871675

ABSTRACT

Global health, particularly in underserved settings can benefit immensely from well-trained community health workers (CHWs) supporting primary healthcare interventions. They can reduce morbidity and mortality of infectious diseases like malaria. Disease control programs can particularly benefit from a tight link between CHWs and communities and several studies have shown the benefit of the participation of non-facility-based CHWs in malaria control program activities for reducing malaria-related mortality in children. Because CHWs are often part of and trusted by served communities, they can also be an important resource to address challenges faced by their communities. Where post-marketing surveillance systems are underserved, they can relay important information about suspected safety signals and factors affecting therapeutic effectiveness in their communities. The CANTAM-Pyramax® trial was a phase IIIb/ IV cohort event monitoring study conducted at six centers in five African countries. To assess real-world effectiveness and safety of the anti-malarial pyronaridine-artesunate in 8560 malaria episodes, follow-up was not primarily conducted by medical staff but by specifically trained CHWs. This perspective paper discusses how the participation of a CHW workforce can be of benefit for effectiveness trials in limited-resource settings, using the example of the CANTAM-Pyramax trial.


Subject(s)
Antimalarials , Malaria , Child , Humans , Africa , Antimalarials/therapeutic use , Community Health Workers , Malaria/drug therapy , Malaria/prevention & control , Malaria/epidemiology
3.
Eur J Obstet Gynecol Reprod Biol ; 289: 9-18, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37611538

ABSTRACT

BACKGROUND: Women of childbearing age are commonly affected by bacterial vaginosis (BV). Maternal-fetal outcomes associated with BV during pregnancy can be fatal for both the mother and the newborn. AIM: To identify maternal and fetal outcomes in pregnant women with BV encountered globally, highlight their prevalence, and identify maternal-fetal outcomes associated with BV. METHODS: The databases Embase, PubMed, Web of Science and Global Index Medicus were searched from inception until December 2022. No restrictions on time or geographical location were imposed when searching for published articles that examined maternal-fetal outcomes in pregnant women with BV. A random effects model was used to perform the meta-analysis. Sources of heterogeneity were investigated using subgroup analysis, and publication bias was assessed using funnel plots and Egger tests. FINDINGS: In total, 26 of the 8983 articles retrieved from the databases met the inclusion criteria and were included in this study. Twenty-two maternal outcomes and 22 fetal outcomes were recorded among pregnant women with BV worldwide. This study determined the prevalence of maternal-fetal outcomes reported in three or more studies. Among fetal outcomes, preterm birth (PTB) had the highest prevalence [17.9%, 95% confidence interval (CI) 13-23.3%], followed by mechanical ventilation (15.2%, 95% CI 0-45.9%), low birth weight (LBW) (14.2%, 95% CI 9.1-20.1%) and neonatal intensive care unit admission (11.2%, 95% CI 0-53.5%). BV was associated with PTB [odds ratio (OR) 1.76, 95% CI 1.32-2.35], LBW (OR 1.73, 95% CI 1.41-2.12) and birth asphyxia (OR 2.90, 95% CI 1.13-7.46). Among maternal outcomes, premature rupture of membranes (PROM) had the highest prevalence (13.2%, 95% CI 6.1-22.3%). BV was associated with the following maternal outcomes: intrauterine infection (OR 2.26, 95% CI 1.44-3.56), miscarriage (OR 2.34, 95% CI 1.18-4.64) and PROM (OR 2.59, 95% CI 1.39-4.82). Maternal and fetal outcomes were most prevalent in women whose BV was diagnosed using the Amsel criteria (37.2%, 95% CI 23-52.6%) and in the third trimester (29.6%, 95% CI 21.2-38.8%). Although reported in fewer than three studies, some maternal-fetal outcomes are highly prevalent, such as respiratory distress (76.67%, 95% CI 57.72-90.07%), dyspareunia (68.33%, 95% CI 55.04-79.74%) and malodorous discharge (85.00%, 95% CI 73.43-92.90%). CONCLUSION: BV has been associated with several adverse maternal-fetal outcomes around the world. While BV is a common vaginal infection, the types of maternal-fetal outcomes from pregnant women with BV vary by country.


Subject(s)
Abortion, Spontaneous , Premature Birth , Vaginosis, Bacterial , Pregnancy , Female , Infant, Newborn , Humans , Pregnancy Outcome/epidemiology , Vaginosis, Bacterial/complications , Vaginosis, Bacterial/epidemiology , Premature Birth/epidemiology , Pregnant Women
4.
Int J Infect Dis ; 132: 108-117, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37028468

ABSTRACT

OBJECTIVES: This study aimed to investigate the evolution of Plasmodium falciparum antimalarial drug resistance markers by comparing the pre- and post-adoption of artemisinin-based combination therapies (ACTs) in Yaounde, Cameroon. METHODS: The molecular characterization of known antimalarial drug resistance markers (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, and Pfk13) in P. falciparum-positive samples collected in 2014 and 2019-2020 was achieved using nested polymerase chain reaction, followed by targeted amplicon deep sequencing on the Illumina MiSeq platform. Data derived were compared with those published during the pre-ACT adoption period from 2004 to 2006. RESULTS: A high prevalence of Pfmdr1 184F, Pfdhfr 51I/59R/108N, and Pfdhps 437G mutant alleles was observed during the post-ACT adoption period. The Pfcrt 76T and Pfmdr1 86Y mutant alleles significantly declined between 2004 and 2020 (P <0.0001). Conversely, the resistance markers to antifolates, Pfdhfr 51I/59R/108N and Pfdhps 437G, significantly increased during the same study period (P <0.0001). We identified nine mutations in the propeller domains of Pfk13; although they were all present in single parasite isolates, none of them are known to confer artemisinin resistance. CONCLUSION: This study documented a near-complete reversion to sensitive parasites for markers conferring resistance to the 4-aminoquinolines and arylamino alcohols in Yaounde. In contrast, the Pfdhfr mutations associated with pyrimethamine resistance are moving toward saturation.


Subject(s)
Antimalarials , Artemisinins , Malaria, Falciparum , Humans , Antimalarials/pharmacology , Antimalarials/therapeutic use , Plasmodium falciparum/genetics , Cameroon/epidemiology , Sulfadoxine/therapeutic use , Drug Combinations , Malaria, Falciparum/drug therapy , Malaria, Falciparum/parasitology , Artemisinins/pharmacology , Artemisinins/therapeutic use , Protozoan Proteins/genetics
5.
JMIR Res Protoc ; 12: e38213, 2023 Jan 24.
Article in English | MEDLINE | ID: mdl-36692923

ABSTRACT

BACKGROUND: Malaria and HIV, 2 of the world's deadliest diseases, share a lot of territory in sub-Saharan Africa. OBJECTIVE: This study seeks to investigate the effect of HIV on the immune response to malaria infection among pregnant women in Kumba in the southwest region (SWR) of Cameroon. The study aims to determine the prevalence of malaria infection, assess the occurrence of Plasmodium falciparum genetic diversity, and evaluate the antibody (immunoglobulin [Ig]G and IgM: apical membrane antigen-1 [AMA1], merozoite surface protein [MSP]1, MSP2, MSP3, and erythrocyte-binding antigen [EBA]175) and cytokine (interleukin [IL]-10, tumor necrosis factor alpha [TNF-α], and interferon gamma [IFNγ]) response to malaria infection among pregnant women with and without HIV in Kumba. METHODS: The study will be a hospital-based cross-sectional design that will run from March 2022 to February 2023. It will recruit pregnant women with and without HIV who are in their third trimester of pregnancy. The study will be carried out in 5 health institutions in Kumba: General Hospital Kumba, Presbyterian Hospital Kumba, District Hospital Kumba-town, Kossala Integrated Health Center Kumba, and Catholic Hospital Kumba. About 3 mL of the mother's venous blood, placental blood, and baby cord blood will be collected from each pregnant women at the point of delivery. Microscopy, rapid diagnostic tests (RDTs), and nested polymerase chain reaction (PCR) will be performed to identify the malaria parasite in all the samples, and nested PCR targeting the different genetic diversity markers for P. falciparum will also be performed. Furthermore, sequencing will be performed to study the nucleotide sequence of different alleles, and the genetic diversity of the alleles responsible for malaria infection among pregnant women will be assessed. A multiplex assay will be conducted to analyze the peripheral blood plasma and cord blood plasma for the cytokine and total antibody response to malaria infection among pregnant women with and without HIV. The questionnaire for data collection will be pretested at the Kumba District Hospital, and ethical clearance will be obtained from the University of Buea and the Regional Delegation of Public Health for the SWR. Data will be analyzed using SPSS Statistics and STATA. All P values <.05 will be considered statistically significant. BioEdit 7.0.0 software will be used to align the nucleotide sequences of different genes after sequencing. Phylogenetic tree searching will be conducted using the maximum-likelihood (ML) method in MEGA V6.0. RESULTS: The project started in March 2022 and will end in February 2023. Presently, three-fourth of the project funding has been disbursed to date. A total of 218 participants have been enrolled: 193 (88.5%) women without HIV and 25 (11.5%) women with HIV. Between February 2023 and March 2024, the following results will be ready for publication: maternal-neonatal malaria prevalence among pregnant women and babies in Kumba, the effect of HIV on (1) P. falciparum genetic diversity among pregnant women in Kumba, (2) the maternal and neonatal immune response to MSP1, MSP2, and EBA175 IgG antibody response to P. falciparum-caused malaria infection among pregnant women, and (3) the maternal and neonatal pro-inflammatory and anti-inflammatory cytokine response to malaria infection. CONCLUSIONS: HIV infection increases the prevalence of malaria infection among pregnant women and also influences the genetic diversity of P. falciparum, with MSP1 alleles being the most prevalent. HIV infection also reduces the antibody response to malaria infection, as well as altering the level of pro-inflammatory and anti-inflammatory responses to malaria infection. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38213.

6.
J Clin Virol Plus ; 3(4): 100168, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38911322

ABSTRACT

Introduction: While the global COVID-19 pandemic is slowly coming under control, current efforts are focused on understanding the epidemiology of endemic SARS-CoV-2. The tool of choice for doing so remains serological tests that detect SARS-CoV-2 induced antibodies. However, the performance of these tests should be evaluated to ensure they comply with the specific performance criteria desired by each country that they are used in. Methods: Here, we use pre-COVID-19 plasma and plasma from SARS-CoV-2-infected individuals collected in 2020, 2021 and 2022 to evaluate the performance of two commercial Rapid Lateral Flow (RLF) tests (the PANBIO™ COVID-19 IgG/IgM rapid test and the LABNOVATION™ COVID-19 (SARS-CoV-2) IgG/IgM rapid test) and one commercial ELISA test (the PLATELIA™ SARS-CoV-2 total Ab). Results: We find that whereas the specificity of the two RLF tests is ≥ 95%, it was 91% for the ELISA tests. However, at 14 days post-COVID-19 date of diagnosis (DoD), only the ELISA test constantly achieved a sensitivity of ≥80% over all the three years. In addition, the rate of detection of the two RLF tests varied across the years with a sensitivity ranging from <80% in 2021 to >80% in 2022. More importantly the capacity of these two RLF tests to detect IgG antibodies decreased with time. On the contrary, the sensitivity of the ELISA test was still above 80% more than six months post DoD. Conclusion: We recommend that sero-epidemiological surveys focused on testing antibodies should not rely on performances reported by the assay manufacturers. They should include a formal evaluation of the selected assays to ensure its limitations and strengths conform with the data-accuracy requirements of the surveys.

7.
Heliyon ; 8(11): e11861, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36451747

ABSTRACT

The emergence and spread of Plasmodium falciparum (P.f) drug resistance is still a major concern in Sub-Saharan Africa and warrants that its evolution be monitored continuously. The present study aimed at determining the distribution of key P.f drug resistance-mediating alleles in circulating malaria parasites in the West region of Cameroon. A cross sectional hospital-based study was conducted in Dschang and Ngounso in the West region of Cameroon. The Pfcrt, Pfmdr1, and the Pfdhps genes were amplified through nested PCR in 208 malaria-infected samples of the 301 febrile outpatients enrolled. The presence or absence of mutations in the K76T, N86Y, A437G and A581G codons of these P.f. genes respectively were determined through restriction digestion analysis. The proportion of different alleles were estimated as percentages and compared between two study sites using the Chi square test. A p value <0.05 was considered significant. A high prevalence (75.6%) of the 437G allele was observed. It was significantly different between Dschang and Ngounso (62% vs. 89.2%, X2 = 19.6, P = 0.00005). Equally observed was a 19.2% (95%CI: 13.3-25.6) of the dhps-581G mutant allele. Furthermore, we observed the Pfcrt-76T, Pfmdr1-N86 mutations in 73.0% (67.5-79.7) and 87.2% (83.2-91.9), and 3.0% (0.0-9.6) and 12.8% was observed for the Pfcrt-K76T and Pfmdr1-N86Y respectively. When biallelic haplotypes were constructed from alleles of the three genes, same pattern was seen. Overall, 73% and 87% of circulating P. falciparum isolates carried wild type alleles at Pfmdr1-N86Y and Pfcrt-K76T. On the other hand, we found more parasites with mutant alleles at dhps (437G and 581G) loci which may reflect possible drug-related selection of this mutant in the parasite population. Continuous monitoring of these mutations is recommended to pre-empt a loss in sulphadoxine-pyrimethamine efficacy in malaria chemoprevention programs.

8.
Parasit Vectors ; 15(1): 344, 2022 Sep 28.
Article in English | MEDLINE | ID: mdl-36171589

ABSTRACT

BACKGROUND: Malaria remains endemic in Cameroon, with heterogeneous transmission related to eco-climatic variations, vector diversity and spatial distribution. The intensification of malaria prevention and control through the free distribution of insecticide-treated nets in recent years may have altered the composition, geographic distribution and natural infection rate of Anopheles species, with implications for malaria transmission dynamics. The present study seeks to assess the vectorial diversity, dynamics and infectivity across different seasons and altitudes in relationship to parasite prevalence around the slopes of Mount Cameroon, southwestern region. METHOD: Mosquitoes were sampled (indoors and outdoors) in 11 eco-epidemiological settings at low (18-197 m), intermediate (371-584 m) and high (740-1067 m) altitude by nightly human landing catches. The mosquitoes were identified morphologically and Anopheles gambiae sibling species identified by PCR. Parity status was ascertained by examining the ovaries and the entomological inoculation rates (EIR) determined by Plasmodium falciparum circumsporozoite antigen ELISA of the head-thorax. The prevalence of Plasmodium infection across target communities was assessed using rapid diagnostic tests. RESULTS: A total of 7327 (18.0 mosquitoes/trap/night) mosquitoes were trapped, mainly during the rainy season (5678, 77.5%) and at low altitude (3669, 50.1%). Anopheles spp. (5079, 69.3%) was the most abundant genera and An. gambiae complex (2691, 36.7%) the major vector, varying with altitude (χ2 = 183.87, df = 8, P < 0.001) and season (χ2 = 28.14, df = 4, P < 0.001). Only An. gambiae (s.s.) was identified following molecular analysis of An. gambiae complex siblings. The overall biting peak for An. gambiae complex was 2-3 a.m. Anopheles cinctus was the most abundant secondary vector in the area. The average EIR in the area was 2.08 infective bites per person per night (ib/p/n), higher at low (2.45 ib/p/n) than at intermediate altitude (1.39 ib/p/n) and during the rainy (1.76 ib/p/n) compared to the dry season (0.34 ib/p/n). Anopheles funestus was most infectious overall (28.1%, 16/57) while An. gambiae had the highest inoculation rates averaging 1.33 ib/p/n. Most Anopheles species across all altitudes and seasons were parous, highest in communities with the highest proportion of malaria parasite infections. CONCLUSION: Anopheles gambiae (s.s.) remains the major malaria vector in the area and An. cinctus possibly a secondary vector of the disease in the slopes of Mt. Cameroon. The seasonal and altitudinal effects on the distribution of these mosquitoes may have implications for the transmission of malaria and its control strategies in the area. Regular monitoring of the bionomics of local Anopheles vector species and targeted control interventions in the 'hotspots' is necessary to curb the prevalence of the infection and incidence of disease.


Subject(s)
Anopheles , Insecticides , Malaria, Falciparum , Malaria , Animals , Anopheles/parasitology , Cameroon/epidemiology , Feeding Behavior , Humans , Malaria/epidemiology , Malaria, Falciparum/parasitology , Mosquito Vectors/parasitology , Plasmodium falciparum , Protozoan Proteins/analysis
9.
Microorganisms ; 10(6)2022 May 31.
Article in English | MEDLINE | ID: mdl-35744659

ABSTRACT

The tsetse flies, biological vectors of African trypanosomes, harbour a variety of bacteria involved in their vector competence that may help in developing novel vector control tools. This study provides an inventory of tsetse bacterial communities in Cameroon and explores their possible associations with trypanosome establishment in Glossina palpalis palpalis. High throughput sequencing of the V3-V4 hypervariable region of the bacterial 16S rRNA gene, with subsequent metagenomic, multivariate, and association analyses, were used to investigate the levels and patterns of microbial diversity in four tsetse species. Overall, 31 bacterial genera and four phyla were identified. The primary symbiont Wigglesworthia dominated almost all the samples, with an overall relative abundance of 47.29%, and seemed to be replaced by Serratia or Burkholderia in some G. tachinoides flies. Globally, significant differences were observed in the microbiome diversity and composition among tsetse species and between teneral and non-teneral flies, or between flies displaying or not displaying mature trypanosome infections. In addition, differential abundance testing showed some OTUs, or some bacteria taxa, associated with trypanosome maturation in tsetse flies. These bacteria could be further investigated for an understanding of their mechanism of action and alternatively, transformed and used to block trypanosome development in tsetse flies.

10.
PLoS One ; 17(5): e0268820, 2022.
Article in English | MEDLINE | ID: mdl-35594307

ABSTRACT

Human immunodeficiency virus (HIV)-1 infection during pregnancy reduces the transplacental transfer of protective maternal antibodies needed to confer immunity during early postnatal life. However, the mediation of MicroRNA in this dysregulation is not well understood MicroRNAs 3181 and 199a have been shown to mediate neonatal Fc receptor (FcRn)-like transmembrane antibody transfer and endocytosis respectively but their expression levels in the placenta and plasma in women living with HIV have not been extensively investigated. The objective of this study was to determine how the expression levels of miR-3181 and miR-199a in the placenta and plasma are affected in women chronically infected with HIV who are on antiretroviral therapy (ART) and are virally suppressed at delivery. In this pilot case-control study, plasma and placenta biopsies were obtained from 36 (18 HIV+ and 18 HIV-) Cameroonian women at delivery. MicroRNAs 3181 and 199a expression levels were measured using RT-qPCR, data was analyzed using SPSS22.0 and R 3.60, and p values below 0.05 were considered statistically significant. All the HIV-infected women were on known ART regimens and were virally suppressed. There was no significant difference in the levels of miR-3181 (p>0.05) in the placenta and plasma amongst HIV-infected and HIV uninfected women. The expression levels of miR-199a were significantly greater in the plasma compared to the placenta of HIV+ (p = 0.00005) and HIV- (p = 0.027) women. Moreover, there was a significantly higher (p = 0.02) level of miR-199a in the plasma of women with HIV and their uninfected counterparts. Linear regression models adjusted for systolic pressure showed no significant difference (p>0.05) in the levels of miR-199a and miR-3181 in both the placenta and plasma due to HIV infection. Our findings suggest that even though ART uptake and viral suppression might help in maintaining miR3181 and miR199a levels in the placenta of women with HIV at comparative levels to those of their HIV negative counterparts, the significantly higher levels of miR-199a in the plasma of women with HIV compared to the placenta might highlight lurking systemic dangers and requires further investigation.


Subject(s)
HIV Infections , HIV-1 , MicroRNAs , Female , Humans , Infant, Newborn , Pregnancy , Cameroon , Case-Control Studies , HIV Infections/drug therapy , HIV Infections/metabolism , HIV-1/genetics , HIV-1/metabolism , MicroRNAs/metabolism , Placenta/metabolism , Pregnant Women
11.
Pathogens ; 11(2)2022 Feb 15.
Article in English | MEDLINE | ID: mdl-35215196

ABSTRACT

Understanding how multiple insecticide resistance mechanisms occur in malaria vectors is essential for efficient vector control. This study aimed at assessing the evolution of metabolic mechanisms and Kdr L995F/S resistance alleles in Anopheles gambiae s.l. from North Cameroon, following long-lasting insecticidal nets (LLINs) distribution in 2011. Female An. gambiae s.l. emerging from larvae collected in Ouro-Housso/Kanadi, Be-Centre, and Bala in 2011 and 2015, were tested for susceptibility to deltamethrin + piperonyl butoxide (PBO) or SSS-tributyl-phosphoro-thrithioate (DEF) synergists, using the World Health Organization's standard protocol. The Kdr L995F/S alleles were genotyped using Hot Ligation Oligonucleotide Assay. Tested mosquitoes identified using PCR-RFLP were composed of An. arabiensis (68.5%), An. coluzzii (25.5%) and An. gambiae (6%) species. From 2011 to 2015, metabolic resistance increased in Ouro-Housso/Kanadi (up to 89.5% mortality to deltametnrin+synergists in 2015 versus <65% in 2011; p < 0.02), while it decreased in Be-Centre and Bala (>95% mortality in 2011 versus 42-94% in 2015; p < 0.001). Conversely, the Kdr L995F allelic frequencies slightly decreased in Ouro-Housso/Kanadi (from 50% to 46%, p > 0.9), while significantly increasing in Be-Centre and Bala (from 0-13% to 18-36%, p < 0.02). These data revealed two evolutionary trends of deltamethrin resistance mechanisms; non-pyrethroid vector control tools should supplement LLINs in North Cameroon.

12.
BMC Infect Dis ; 22(1): 166, 2022 Feb 21.
Article in English | MEDLINE | ID: mdl-35189818

ABSTRACT

BACKGROUND: Many studies have reported high efficacy and safety of artesunate-amodiaquine (AS-AQ) and artemether-lumefantrine (AL) when administered under direct observation in Cameroon. There is paucity of data to support their continuous use in home-based treatment of uncomplicated Plasmodium falciparum malaria in Cameroon. Hence, this study aimed to assess the effectiveness and safety of AS-AQ versus AL for home-based treatment of uncomplicated P. falciparum malaria among children 6-120 months in Yaoundé, Cameroon. METHODS: A two-arm, open-label, randomized, controlled trial comparing the equivalence of AS-AQ (experimental group) and AL (control group) was carried out from May 2019 to April 2020 at two secondary hospitals in Yaoundé. Participants were randomized to receive either AS-AQ or AL. After the first dose, antimalarial drugs were given at home, rather than under direct observation by a study staff. The conventional on-treatment and post-treatment laboratory and clinical evaluations were not done until day 3 of the full antimalarial treatment course. The evaluation of effectiveness was mainly based on per protocol polymerase chain reaction adjusted adequate clinical and parasitological response (PP PCR adjusted ACPR) on day 28 post-treatment. Safety was based on assessment of adverse events (AEs) and severe adverse events (SAEs) from day 1 to day 28. RESULTS: A total of 242 children were randomized to receive AS-AQ (n = 114) and AL (n = 128). The PP PCR adjusted day 28 cure rates were [AS-AQ = 96.9% (95% CI, 91.2-99.4) versus AL = 95.5% (95% CI, 89.9-98.5), P = 0.797]. Expected mild to moderate adverse events were reported in both arms [AS-AQ = 83 (84.7%) versus AL = 99 (86.1%), P = 0.774]. The most common adverse events included: transient changes of hematologic indices and fever. CONCLUSIONS: This study demonstrated that AS-AQ and AL are effective and safe for home management of malaria in Yaoundé. The evidence from this study supports the parallel use of the two drugs in routine practice. However, the findings from this study do not describe the likely duration of antimalarial effectiveness in holoendemic areas where multiple courses of treatment might be required. TRIAL REGISTRATION: This study is a randomized controlled trial and it was retrospectively registered on 23/09/2020 at ClinicalTrials.gov with registration number NCT04565184.


Subject(s)
Antimalarials , Artemisinins , Malaria, Falciparum , Amodiaquine/adverse effects , Antimalarials/adverse effects , Artemether/therapeutic use , Artemether, Lumefantrine Drug Combination/therapeutic use , Artemisinins/adverse effects , Artesunate/therapeutic use , Cameroon , Child , Drug Combinations , Ethanolamines/adverse effects , Humans , Infant , Malaria, Falciparum/drug therapy , Plasmodium falciparum , Treatment Outcome
13.
Diagnostics (Basel) ; 11(9)2021 Aug 27.
Article in English | MEDLINE | ID: mdl-34573898

ABSTRACT

BACKGROUND: There was an increase in the number of malaria cases in Cameroon in 2018 that could reflect changes in provider practice, despite effective interventions. In this study, we assessed the diagnostic performance of two malaria rapid diagnostic tests (mRDTs) for diagnostic confirmation of suspected cases of malaria in public and private health facilities in two malaria transmission settings in Cameroon. METHODS: We evaluated the diagnostic performance of CareStart pf and SD Bioline Pf/PAN mRDT and compared these parameters by RDT type and transmission setting. Nested PCR and blood film microscopy were used as references. The chi square test was used for independent sample comparisons, while the McNemar's test was used to test for the dependence of categorical data in paired sample testing. A p < 0.05 was considered significant in all comparisons. The R (v.4.0.2) software was used for analyses. RESULTS: A total of 1126 participants consented for the study in the four sites. The diagnostic accuracy of the CareStart Pf mRDT was 0.93.6% (0.911-0.961) in Yaoundé, 0.930% (0.90-0.960) in Ngounso, 0.84% (0.794-0.891) in St Vincent Catholic Hospital Dschang and 0.407 (0.345-0.468) in Dschang district hospital. For SD Bioline Pf/PAN the accuracy was 0.759 (0.738-0.846) for St Vincent Catholic Hospital Dschang and 0.426 (0.372-0.496) for the Dschang district hospital. The accuracy was slightly lower in each case but not statistically different when PCR was considered as the reference. The likelihood ratios of the positive and negative tests were high in the high transmission settings of Yaoundé (10.99 (6.24-19.35)) and Ngounso (14.40 (7.89-26.28)) compared to the low transmission settings of Dschang (0.71 (0.37-1.37)) and St Vincent Catholic hospital (7.37 (4.32-12.59)). There was a high degree of agreement between the tests in Yaoundé (Cohen's Kappa: 0.85 ± 0.05 (0.7-0.95)) and Ngounso (Cohen's Kappa: 0.86 ± 0.05 (0.74, 0.97)) and moderate agreement in St Vincent hospital Dschang (k: 0.58 ± 0.06 (0.44-0.71)) and poor agreement in the District Hospital Dschang (Cohen's Kappa: -0.11 ± 0.05 (-0.21-0.01)). The diagnostic indicators of the SD Bioline Pf/PAN were slightly better than for CareStart Pf mRDT in St Vincent Catholic hospital Dschang, irrespective of the reference test. CONCLUSIONS: Publicly procured malaria rapid diagnostic tests in Cameroon have maintained high accuracy (91-94%) in the clinical diagnosis of malaria in high malaria transmission regions of Cameroon, although they failed to reach WHO standards. We observed an exception in the low transmission region of Dschang, West region, where the accuracy tended to be lower and variable between facilities located in this town. These results underscore the importance of the routine monitoring of the quality and performance of malaria RDTs in diverse settings in malaria endemic areas.

14.
Insect Biochem Mol Biol ; 138: 103647, 2021 11.
Article in English | MEDLINE | ID: mdl-34530119

ABSTRACT

The overexpression and overactivity of key cytochrome P450s (CYP450) genes are major drivers of metabolic resistance to insecticides in African malaria vectors such as Anopheles funestus s.s. Previous RNAseq-based transcription analyses revealed elevated expression of CYP325A specific to Central African populations but its role in conferring resistance has not previously been demonstrated. In this study, RT-qPCR consistently confirmed that CYP325A is highly over-expressed in pyrethroid-resistant An. funestus from Cameroon, compared with a control strain and insecticide-unexposed mosquitoes. A synergist bioassay with PBO significantly recovered susceptibility for permethrin and deltamethrin indicating P450-based metabolic resistance. Analyses of the coding sequence of CYP325A Africa-wide detected high-levels of polymorphism, but with no predominant alleles selected by pyrethroid resistance. Geographical amino acid changes were detected notably in Cameroon. In silico homology modelling and molecular docking simulations predicted that CYP325A binds and metabolises type I and type II pyrethroids. Heterologous expression of recombinant CYP325A and metabolic assays confirmed that the most-common Cameroonian haplotype metabolises both type I and type II pyrethroids with depletion rate twice that the of the DR Congo haplotype. Analysis of the 1 kb putative promoter of CYP325A revealed reduced diversity in resistant mosquitoes compared to susceptible ones, suggesting a potential selective sweep in this region. The establishment of CYP325A as a pyrethroid resistance metabolising gene further explains pyrethroid resistance in Central African populations of An. funestus. Our work will facilitate future efforts to detect the causative resistance markers in the promoter region of CYP325A to design field applicable DNA-based diagnostic tools.


Subject(s)
Anopheles/genetics , Cytochrome P-450 Enzyme System/genetics , Insect Proteins/genetics , Insecticide Resistance/genetics , Insecticides/pharmacology , Mosquito Vectors/genetics , Pyrethrins/pharmacology , Africa, Central , Animals , Anopheles/metabolism , Computer Simulation , Cytochrome P-450 Enzyme System/metabolism , Female , Insect Proteins/metabolism , Malaria/transmission , Molecular Docking Simulation , Mosquito Vectors/metabolism
15.
Sci Rep ; 11(1): 17101, 2021 08 24.
Article in English | MEDLINE | ID: mdl-34429446

ABSTRACT

The rapid expansion of insecticide resistance and outdoor malaria transmission are affecting the efficacy of current malaria control measures. In urban settings, where malaria transmission is focal and breeding habitats are few, fixed and findable, the addition of anti-larval control measures could be efficient for malaria vector control. But field evidences for this approach remains scarce. Here we provide findings of a randomized-control larviciding trial conducted in the city of Yaoundé that support the efficacy of this approach. A two arms random control trial design including 26 clusters of 2 to 4 km2 each (13 clusters in the intervention area and 13 in the non-intervention area) was used to assess larviciding efficacy. The microbial larvicide VectoMax combining Bacillus thuringiensis var israelensis (Bti) and Bacillus sphaericus in a single granule was applied every 2 weeks in all standing water collection points. The anopheline density collected using CDC light traps was used as the primary outcome, secondary outcomes included the entomological inoculation rate, breeding habitats with anopheline larvae, and larval density. Baseline entomological data collection was conducted for 17 months from March 2017 to July 2018 and the intervention lasted 26 months from September 2018 to November 2020. The intervention was associated with a reduction of 68% of adult anopheline biting density and of 79% of the entomological inoculation rate (OR 0.21; 95% CI 0.14-0.30, P < 0.0001). A reduction of 68.27% was recorded for indoor biting anophelines and 57.74% for outdoor biting anophelines. No impact on the composition of anopheline species was recorded. A reduction of over 35% of adult Culex biting densities was recorded. The study indicated high efficacy of larviciding for reducing malaria transmission intensity in the city of Yaoundé. Larviciding could be part of an integrated control approach for controlling malaria vectors and other mosquito species in the urban environment.


Subject(s)
Anopheles/drug effects , Bacterial Toxins/toxicity , Insecticides/toxicity , Malaria/prevention & control , Mosquito Vectors/drug effects , Animals , Anopheles/growth & development , Anopheles/physiology , Bacterial Toxins/administration & dosage , Biomass , Cameroon , Housing/statistics & numerical data , Humans , Insect Bites and Stings/epidemiology , Insecticides/administration & dosage , Larva/drug effects , Mosquito Vectors/growth & development , Mosquito Vectors/physiology , Urban Population/statistics & numerical data
16.
PLoS Med ; 18(6): e1003669, 2021 06.
Article in English | MEDLINE | ID: mdl-34129601

ABSTRACT

BACKGROUND: In Phase II/III randomized controlled clinical trials for the treatment of acute uncomplicated malaria, pyronaridine-artesunate demonstrated high efficacy and a safety profile consistent with that of comparators, except that asymptomatic, mainly mild-to-moderate transient increases in liver aminotransferases were reported for some patients. Hepatic safety, tolerability, and effectiveness have not been previously assessed under real-world conditions in Africa. METHODS AND FINDINGS: This single-arm, open-label, cohort event monitoring study was conducted at 6 health centers in Cameroon, Democratic Republic of Congo, Gabon, Ivory Coast, and Republic of Congo between June 2017 and April 2019. The trial protocol as closely as possible resembled real-world clinical practice for the treatment of malaria at the centers. Eligible patients were adults or children of either sex, weighing at least 5 kg, with acute uncomplicated malaria who did not have contraindications for pyronaridine-artesunate treatment as per the summary of product characteristics. Patients received fixed-dose pyronaridine-artesunate once daily for 3 days, dosed by body weight, without regard to food intake. A tablet formulation was used in adults and adolescents and a pediatric granule formulation in children and infants under 20 kg body weight. The primary outcome was the hepatic event incidence, defined as the appearance of the clinical signs and symptoms of hepatotoxicity confirmed by a >2× rise in alanine aminotransferase/aspartate aminotransferase (ALT/AST) versus baseline in patients with baseline ALT/AST >2× the upper limit of normal (ULN). As a secondary outcome, this was assessed in patients with ALT/AST >2× ULN prior to treatment versus a matched cohort of patients with normal baseline ALT/AST. The safety population comprised 7,154 patients, of mean age 13.9 years (standard deviation (SD) 14.6), around half of whom were male (3,569 [49.9%]). Patients experienced 8,560 malaria episodes; 158 occurred in patients with baseline ALT/AST elevations >2×ULN. No protocol-defined hepatic events occurred following pyronaridine-artesunate treatment of malaria patients with or without baseline hepatic dysfunction. Thus, no cohort comparison could be undertaken. Also, as postbaseline clinical chemistry was only performed where clinically indicated, postbaseline ALT/AST levels were not systematically assessed for all patients. Adverse events of any cause occurred in 20.8% (1,490/7,154) of patients, most frequently pyrexia (5.1% [366/7,154]) and vomiting (4.2% [303/7,154]). Adjusting for Plasmodium falciparum reinfection, clinical effectiveness at day 28 was 98.6% ([7,369/7,746] 95% confidence interval (CI) 98.3 to 98.9) in the per-protocol population. There was no indication that comorbidities or malnutrition adversely affected outcomes. The key study limitation was that postbaseline clinical biochemistry was only evaluated when clinically indicated. CONCLUSIONS: Pyronaridine-artesunate had good tolerability and effectiveness in a representative African population under conditions similar to everyday clinical practice. These findings support pyronaridine-artesunate as an operationally useful addition to the management of acute uncomplicated malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT03201770.


Subject(s)
Antimalarials/therapeutic use , Artesunate/therapeutic use , Malaria/drug therapy , Naphthyridines/therapeutic use , Adolescent , Adult , Africa , Antimalarials/adverse effects , Artesunate/adverse effects , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/etiology , Child , Child, Preschool , Drug Combinations , Female , Humans , Infant , Infant, Newborn , Liver Function Tests , Malaria/diagnosis , Malaria/parasitology , Male , Naphthyridines/adverse effects , Patient Safety , Product Surveillance, Postmarketing , Retrospective Studies , Time Factors , Treatment Outcome , Young Adult
17.
Trop Med Health ; 49(1): 41, 2021 May 21.
Article in English | MEDLINE | ID: mdl-34020717

ABSTRACT

BACKGROUND: Genotyping is a powerful tool for investigating outbreaks of infectious diseases and it can provide useful information such as identifying the source and route of transmission, and circulating strains involved in the outbreak. Genotyping techniques based on variable number of tandem repeats (VNTR) are instrumental in detecting heterogeneity in Mycobacterium ulcerans (MU) and also for discriminating MU from other mycobacteria species. Here, we describe and map the distribution of MU genotypes in Buruli ulcer (BU) endemic communities of the Nyong valley in Cameroon. We also tested the hypothesis of whether the suspected animal reservoirs of BU that share the human microhabitat are shedding contaminated fecal matters and saliva into their surrounding environments. METHODS: Environmental samples from suspected MU-risk factors and lesion swabs from human patients were sampled in BU-endemic communities and tested for the presence of MU by qPCR targeting three independent sequences (IS2404, IS2606, KR-B). Positive samples to MU were further genotyped by VNTR with confirmation by sequencing of four loci (MIRU1, Locus 6, ST1, Locus 19). RESULTS: MU was detected in environmental samples including water bodies (23%), biofilms (14%), detritus (10%), and in human patients (73%). MU genotypes D, W, and C were found both in environmental and human samples. The micro geo-distribution of MU genotypes from communities showed that genotype D is found both in environmental and human samples, while genotypes W and C are specific to environmental samples and human lesions, respectively. No obvious focal grouping of MU genotypes was observed at the community scale. An additional survey in the human microhabitat suggests that domestic and wild animals do not shed MU in their saliva and feces in sampled communities. CONCLUSIONS: VNTR typing uncovered different MU genotypes circulating in the endemic communities of the Akonolinga district. A MU environmental genotype was found in patients, yet the mechanism of contamination remains to be investigated; and recovering MU in culture from the environment remains key priority to enable a better understanding of the mode of transmission of BU. We also conclude that excretions from suspected animals are unlikely to be major sources of MU in the Nyong Valley in Cameroon.

18.
Malar J ; 20(1): 32, 2021 Jan 09.
Article in English | MEDLINE | ID: mdl-33422080

ABSTRACT

BACKGROUND: Malaria remains highly endemic in Cameroon. The rapid emergence and spread of drug resistance was responsible for the change from monotherapies to artemisinin-based combinations. This systematic review and meta-analysis aimed to determine the prevalence and distribution of Plasmodium falciparum drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon from January 1998 to August 2020. METHODS: The PRISMA-P and PRISMA statements were adopted in the inclusion of studies on single nucleotide polymorphisms (SNPs) of P. falciparum anti-malarial drug resistance genes (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, Pfatp6, Pfcytb and Pfk13). The heterogeneity of the included studies was evaluated using the Cochran's Q and I2 statistics. The random effects model was used as standard in the determination of heterogeneity between studies. RESULTS: Out of the 902 records screened, 48 studies were included in this aggregated meta-analysis of molecular data. A total of 18,706 SNPs of the anti-malarial drug resistance genes were genotyped from 47,382 samples which yielded a pooled prevalence of 35.4% (95% CI 29.1-42.3%). Between 1998 and 2020, there was significant decline (P < 0.0001 for all) in key mutants including Pfcrt 76 T (79.9%-43.0%), Pfmdr1 86Y (82.7%-30.5%), Pfdhfr 51I (72.2%-66.9%), Pfdhfr 59R (76.5%-67.8%), Pfdhfr 108 N (80.8%-67.6%). The only exception was Pfdhps 437G which increased over time (30.4%-46.9%, P < 0.0001) and Pfdhps 540E that remained largely unchanged (0.0%-0.4%, P = 0.201). Exploring mutant haplotypes, the study observed a significant increase in the prevalence of Pfcrt CVIET mixed quintuple haplotype from 57.1% in 1998 to 57.9% in 2020 (P < 0.0001). In addition, within the same study period, there was no significant change in the triple Pfdhfr IRN mutant haplotype (66.2% to 67.3%, P = 0.427). The Pfk13 amino acid polymorphisms associated with artemisinin resistance were not detected. CONCLUSIONS: This review reported an overall decline in the prevalence of P. falciparum gene mutations conferring resistance to 4-aminoquinolines and amino alcohols for a period over two decades. Resistance to artemisinins measured by the presence of SNPs in the Pfk13 gene does not seem to be a problem in Cameroon. Systematic review registration PROSPERO CRD42020162620.


Subject(s)
Antimalarials/pharmacology , Drug Resistance/drug effects , Genetic Markers/genetics , Plasmodium falciparum/genetics , Polymorphism, Single Nucleotide , Cameroon , Plasmodium falciparum/drug effects
19.
PLoS One ; 15(11): e0242012, 2020.
Article in English | MEDLINE | ID: mdl-33170876

ABSTRACT

BACKGROUND: Co-infection with malaria and intestinal parasites is common in children in Africa and may affect their immune response to a malaria parasite infection. Prior studies suggest that co-infections may lead to increased susceptibility to malaria infection and disease severity; however, other studies have shown the reverse. Knowledge on how co-morbidities specifically affect the immune response to malaria antigens is limited. Therefore, this study sought to determine the prevalence of co-infection of malaria and intestinal parasites and its association with antibody levels to malaria merozoite antigens. METHODS: A cross sectional study was carried out in two villages with high transmission of malaria in Cameroon (Ngali II and Mfou) where mass drug administration (MDA) had been administered at ~6-month intervals (generally with albendazole or mebendazole). Children aged 1-15 years were enrolled after obtaining parental consent. A malaria rapid diagnostic test was used on site. Four (4) ml of peripheral blood was collected from each participant to determine Plasmodium falciparum infections by microscopy, haemoglobin levels and serology. Fresh stool samples were collected and examined by wet mount, Kato-Katz method and modified Ritchie concentration techniques. A Multiplex Analyte Platform assay was used to measure antibody levels. RESULTS: A total of 320 children were enrolled. The prevalence of malaria by blood smear was 76.3% (244/320) and prevalence of malaria and intestinal parasites was 16.9% (54/320). Malaria prevalence was highest in young children; whereas, intestinal parasites (IP+) were not present until after 3 years of age. All children positive for malaria had antibodies to MSP142, MSP2, MSP3 and EBA175. No difference in antibody levels in children with malaria-co infections compared to malaria alone were found, except for antibody levels to EBA-175 were higher in children co-infected with intestinal protozoa (p = 0.018), especially those with Entamoeba histolytica infections (p = 0.0026). CONCLUSION: Antibody levels to EBA175 were significantly higher in children co-infected with malaria and E. histolytica compared to children infected with malaria alone. It is important to further investigate why and how the presence of these protozoans might modulate the immune response to malaria antigens.


Subject(s)
Coinfection/epidemiology , Intestinal Diseases, Parasitic/epidemiology , Malaria, Falciparum/epidemiology , Adolescent , Animals , Antibodies, Protozoan/blood , Antibody Formation , Antigens, Protozoan/immunology , Cameroon/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Immunoglobulin G/blood , Immunologic Tests , Infant , Malaria/epidemiology , Malaria/immunology , Malaria/parasitology , Malaria, Falciparum/immunology , Malaria, Falciparum/parasitology , Male , Merozoites/immunology , Parasites/immunology , Plasmodium falciparum/immunology , Prevalence , Protozoan Proteins/immunology
20.
Malar J ; 19(1): 172, 2020 May 03.
Article in English | MEDLINE | ID: mdl-32362282

ABSTRACT

BACKGROUND: This study evaluated the effectiveness of improved housing on indoor residual mosquito density and exposure to infected Anophelines in Minkoameyos, a rural community in southern forested Cameroon. METHODS: Following the identification of housing factors affecting malaria prevalence in 2013, 218 houses were improved by screening the doors and windows, installing plywood ceilings on open eaves and closing holes on walls and doors. Monthly entomological surveys were conducted in a sample of 21 improved and 21 non-improved houses from November 2014 to October 2015. Mosquitoes sampled from night collections on human volunteers were identified morphologically and their parity status determined. Mosquito infectivity was verified through Plasmodium falciparum CSP ELISA and the average entomological inoculation rates determined. A Reduction Factor (RF), defined as the ratio of the values for mosquitoes collected outdoor to those collected indoor was calculated in improved houses (RFI) and non-improved houses (RFN). An Intervention Effect (IE = RFI/RFN) measured the true effect of the intervention. Chi square test was used to determine variable significance. The threshold for statistical significance was set at P < 0.05. RESULTS: A total of 1113 mosquitoes were collected comprising Anopheles sp (58.6%), Culex sp (36.4%), Aedes sp (2.5%), Mansonia sp (2.4%) and Coquillettidia sp (0.2%). Amongst the Anophelines were Anopheles gambiae sensu lato (s.l.) (95.2%), Anopheles funestus (2.9%), Anopheles ziemanni (0.2%), Anopheles brohieri (1.2%) and Anopheles paludis (0.5%). Anopheles gambiae sensu stricto (s.s.) was the only An. gambiae sibling species found. The intervention reduced the indoor Anopheles density by 1.8-fold (RFI = 3.99; RFN = 2.21; P = 0.001). The indoor density of parous Anopheles was reduced by 1.7-fold (RFI = 3.99; RFN = 2.21; P = 0.04) and that of infected Anopheles by 1.8-fold (RFI = 3.26; RFN = 1.78; P = 0.04). Indoor peak biting rates were observed between 02 a.m. to 04 a.m. in non-improved houses and from 02 a.m. to 06 a.m. in improved houses. CONCLUSION: Housing improvement contributed to reducing indoor residual anopheline density and malaria transmission. This highlights the need for policy specialists to further evaluate and promote aspects of house design as a complementary control tool that could reduce indoor human-vector contact and malaria transmission in similar epidemiological settings.


Subject(s)
Anopheles/physiology , Communicable Disease Control/methods , Housing/statistics & numerical data , Malaria/transmission , Mosquito Vectors/physiology , Animals , Cameroon , Humans , Malaria/prevention & control , Population Density , Rural Population
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