Blantyre, Malawi
Blantyre, Malawi

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Chanda E.,National Malaria Control Center | Mzilahowa T.,Malaria Alert Center | Cuamba N.,National Institute of Health
BMC Genomics | Year: 2014

Background: Pyrethroid resistance in the major malaria vector Anopheles funestus is rapidly expanding across Southern Africa. It remains unknown whether this resistance has a unique origin with the same molecular basis or is multifactorial. Knowledge of the origin, mechanisms and evolution of resistance are crucial to designing successful resistance management strategies. Results: Here, we established the resistance profile of a Zambian An. funestus population at the northern range of the resistance front. Similar to other Southern African populations, Zambian An. funestus mosquitoes are resistant to pyrethroids and carbamate, but in contrast to populations in Mozambique and Malawi, these insects are also DDT resistant. Genome-wide microarray-based transcriptional profiling and qRT-PCR revealed that the cytochrome P450 gene CYP6M7 is responsible for extending pyrethroid resistance northwards. Indeed, CYP6M7 is more over-expressed in Zambia [fold-change (FC) 37.7; 13.2 for qRT-PCR] than CYP6P9a (FC15.6; 8.9 for qRT-PCR) and CYP6P9b (FC11.9; 6.5 for qRT-PCR), whereas CYP6P9a and CYP6P9b are more highly over-expressed in Malawi and Mozambique. Transgenic expression of CYP6M7 in Drosophila melanogaster coupled with in vitro assays using recombinant enzymes and assessments of kinetic properties demonstrated that CYP6M7 is as efficient as CYP6P9a and CYP6P9b in conferring pyrethroid resistance. Polymorphism patterns demonstrate that these genes are under contrasting selection forces: the exceptionally diverse CYP6M7 likely evolves neutrally, whereas CYP6P9a and CYP6P9b are directionally selected. The higher variability of CYP6P9a and CYP6P9b observed in Zambia supports their lesser role in resistance in this country.Conclusion: Pyrethroid resistance in Southern Africa probably has multiple origins under different evolutionary forces, which may necessitate the design of different resistance management strategies. © 2014 Riveron et al.; licensee BioMed Central Ltd.

Rehman A.M.,London School of Hygiene and Tropical Medicine | Schwabe C.,Medical Care Development International | Baltazar G.,Medical Care Development International | Matias A.,Medical Care Development International | And 7 more authors.
PLoS ONE | Year: 2011

Background: Insecticide treated nets (ITN) and indoor residual spraying (IRS) are the two pillars of malaria vector control in Africa, but both interventions are beset by quality and coverage concerns. Data from three control programs were used to investigate the impact of: 1) the physical deterioration of ITNs, and 2) inadequate IRS spray coverage, on their respective protective effectiveness. Methods: Malaria indicator surveys were carried out in 2009 and 2010 in Bioko Island, mainland Equatorial Guinea and Malawi to monitor infection with P.falciparum in children, mosquito net use, net condition and spray status of houses. Nets were classified by their condition. The association between infection and quality and coverage of interventions was investigated. Results: There was reduced odds of infection with P.falciparum in children sleeping under ITNs that were intact (Odds ratio (OR): 0.65, 95% CI: 0.55-0.77 and OR: 0.81, 95% CI: 0.56-1.18 in Equatorial Guinea and in Malawi respectively), but the protective effect became less with increasingly worse condition of the net. There was evidence for a linear trend in infection per category increase in deterioration of nets. In Equatorial Guinea IRS offered protection to those in sprayed and unsprayed houses alike when neighbourhood spray coverage was high (≥80%) compared to those living in areas of low IRS coverage (<20%), regardless of whether the house they lived in was sprayed or not (adjusted OR = 0.54, 95% CI 0.33-0.89). ITNs provided only personal protection, offering no protection to non users. Although similar effects were seen in Malawi, the evidence was much weaker than in Equatorial Guinea. Conclusions: Universal coverage strategies should consider policies for repair and replacement of holed nets and promote the care of nets by their owners. IRS programs should ensure high spray coverage since inadequate coverage gives little or no protection at all. © 2011 Rehman et al.

Chinkhumba J.,Malaria Alert Center | Skarbinski J.,Centers for Disease Control and Prevention | Chilima B.,Community Health science Unit | Campbell C.,Centers for Disease Control and Prevention | And 6 more authors.
Malaria Journal | Year: 2010

Background. Malaria rapid diagnostics tests (RDTs) can increase availability of laboratory-based diagnosis and improve the overall management of febrile patients in malaria endemic areas. In preparation to scale-up RDTs in health facilities in Malawi, an evaluation of four RDTs to help guide national-level decision-making was conducted. Methods. A cross sectional study of four histidine rich-protein-type-2- (HRP2) based RDTs at four health centres in Blantyre, Malawi, was undertaken to evaluate the sensitivity and specificity of RDTs, assess prescriber adherence to RDT test results and explore operational issues regarding RDT implementation. Three RDTs were evaluated in only one health centre each and one RDT was evaluated in two health centres. Light microscopy in a reference laboratory was used as the gold standard. Results. A total of 2,576 patients were included in the analysis. All of the RDTs tested had relatively high sensitivity for detecting any parasitaemia [Bioline SD (97%), First response malaria (92%), Paracheck (91%), ICT diagnostics (90%)], but low specificity [Bioline SD (39%), First response malaria (42%), Paracheck (68%), ICT diagnostics (54%)]. Specificity was significantly lower in patients who self-treated with an anti-malarial in the previous two weeks (odds ratio (OR) 0.5; p-value < 0.001), patients 5-15 years old versus patients > 15 years old (OR 0.4, p-value < 0.001) and when the RDT was performed by a community health worker versus a laboratory technician (OR 0.4; p-value < 0.001). Health workers correctly prescribed anti-malarials for patients with positive RDT results, but ignored negative RDT results with 58% of patients with a negative RDT result treated with an anti-malarial. Conclusions. The results of this evaluation, combined with other published data and global recommendations, have been used to select RDTs for national scale-up. In addition, the study identified some key issues that need to be further delineated: the low field specificity of RDTs, variable RDT performance by different cadres of health workers and the need for a robust quality assurance system. Close monitoring of RDT scale-up will be needed to ensure that RDTs truly improve malaria case management. © 2010 Chinkhumba et al; licensee BioMed Central Ltd.

Mzilahowa T.,Malawi Liverpool Wellcome Trust Clinical Research Programme | Mzilahowa T.,Malaria Alert Center | Molyneux M.E.,Malawi Liverpool Wellcome Trust Clinical Research Programme | Molyneux M.E.,Malaria Alert Center
Malaria Journal | Year: 2012

Background: Although malaria is highly prevalent throughout Malawi, little is known of its transmission dynamics. This paper describes the seasonal activity of the different vectors, human biting indices, sporozoite rates and the entomological inoculation rate in a low-lying rural area in southern Malawi. Methods. Vectors were sampled over 52 weeks from January 2002 to January 2003, by pyrethrum knockdown catch in two villages in Chikhwawa district, in the Lower Shire Valley. Results: In total, 7,717 anophelines were collected of which 55.1% were Anopheles gambiae sensu lato and 44.9% were Anopheles funestus. Three members of the An. gambiae complex were identified by PCR: Anopheles arabiensis (75%) was abundant throughout the year, An. gambiae s.s. (25%) was most common during the wet season and Anopheles quadriannulatus occurred at a very low frequency (n=16). An. funestus was found in all samples but was most common during the dry season. Anopheles gambiae s.s. and An. funestus were highly anthropophilic with human blood indices of 99.2% and 96.3%, respectively. Anopheles arabiensis had fed predominantly on humans (85.0%) and less commonly on cattle (10.9%; 1.2% of blood meals were of mixed origin). Plasmodium falciparum (192/3,984) and Plasmodium malariae (1/3,984) sporozoites were detected by PCR in An. arabiensis (3.2%) and An. funestus (4.5%), and in a significantly higher proportion of An. gambiae s.s. (10.6%)(p<0.01). All three vectors were present throughout the year and malaria transmission occurred in every month, although with greatest intensity during the rainy season (January to April). The combined human blood index exceeded 92% and the P. falciparum sporozoite rate was 4.8%, resulting in estimated inoculation rates of 183 infective bites/ person per annum, or an average rate of ∼15 infective bites/person/month. Conclusions: The results demonstrate the importance of An. gambiae s.s., An. arabiensis and An. funestus in driving the high levels of malaria transmission in the south of Malawi. Sustained and high coverage or roll out of current approaches to malaria control (primarily insecticide-treated bed nets and indoor residual house spraying) in the area are likely to reduce the observed high malaria transmission rate and consequently the incidence of human infections, unless impeded by increasing resistance of vectors to insecticides. © 2012 Mzilahowa et al.; licensee BioMed Central Ltd.

Mathanga D.,Malaria Alert Center | Witte D.,University of Liverpool
Archives of Disease in Childhood | Year: 2012

Clinical trials in children in resource-poor environments are essential for local health policy and practice to be relevant and evidence based. Research must be ethical, appropriate, relevant and of good quality. It should, where possible, benefit the subjects studied,the clinical, scientific and support staff involved, and the service and academic institutions of the host country. The challenge for researchers and their sponsors is to maximise such benefits while avoiding the many possible pitfalls.

Chanda E.,Malaria Vector Control Consultant | Mzilahowa T.,Malaria Alert Center | Chipwanya J.,Ministry of Health | Mulenga S.,Ministry of Health | And 5 more authors.
Malaria Journal | Year: 2015

Background: In the past decade, there has been rapid scale-up of insecticide-based malaria vector control in the context of integrated vector management (IVM) according to World Health Organization recommendations. Endemic countries have deployed indoor residual spraying (IRS) and long-lasting insecticidal nets as hallmark vector control interventions. This paper discusses the successes and continued challenges and the way forward for the IRS programme in Malawi. Case description: The National Malaria Control Programme in Malawi, with its efforts to implement an integrated approach to malaria vector control, was the 'case' for this study. Information sources included all available data and accessible archived documentary records on IRS in Malawi. A methodical assessment of published and unpublished documents was conducted via a literature search of online electronic databases. Discussion: Malawi has implemented IRS as the main malaria transmission-reducing intervention. However, pyrethroid and carbamate resistance in malaria vectors has been detected extensively across the country and has adversely affected the IRS programme. Additionally, IRS activities have been characterized by substantial inherent logistical and technical challenges culminating into missed targets. As a consequence, programmatic IRS operations have been scaled down from seven districts in 2010 to only one district in 2014. The future of the IRS programme in Malawi is uncertain due to limited funding, high cost of alternative insecticides and technical resource challenges being experienced in the country. Conclusions: The availability of a long-lasting formulation of the organophosphate pirimiphos-methyl makes the re-introduction of IRS a possibility and may be a useful approach for the management of pyrethroid resistance. Implementing the IVM strategy, advocating for sustainable domestic funding, including developing an insecticide resistance monitoring and management plan and vector surveillance guidelines will be pivotal in steering entomologic monitoring and future vector control activities in Malawi. © 2015 Chanda et al.

Lindblade K.A.,Centers for Disease Control and Prevention | Mwandama D.,Malaria Alert Center | Mzilahowa T.,Malaria Alert Center | Steinhardt L.,Centers for Disease Control and Prevention | And 9 more authors.
Malaria Journal | Year: 2015

Background: Insecticide-treated bed nets (ITNs) are the cornerstone of malaria control in sub-Saharan Africa but their effectiveness may be compromised by the spread of pyrethroid resistance among malaria vectors. The objective of this investigation was to assess the effectiveness of ITNs to prevent malaria in an area of Malawi with moderate pyrethroid resistance. Methods: One deltamethrin ITN was distributed in the study area for every two individuals in each household plus one extra ITN for households with an odd number of residents. A fixed cohort of 1,199 children aged six to 59 months was seen monthly for one year and at sick visits to measure malaria infection and use of ITNs. nsecticide resistance among malaria vectors was measured. The effect of ITN use on malaria incidence was assessed, adjusting for potential confounders using generalized estimating equations accounting for repeated measures. Results: There were 1,909 infections with Plasmodium falciparum over 905 person-years at risk (PYAR), resulting in an observed incidence of 2.1 infections per person-year (iPPY). ITNs were used during 97% of the PYAR. The main vector was Anopheles funestus: mortality in WHO tube assays after exposure to 0.05% deltamethrin was 38% (95% confidence interval (CI) 29-47), and resistance was due to elevated oxidase enzymes. After adjusting for potential confounders, the incidence of malaria infection among ITN users was 1.7 iPPY (95% CI 1.5-2.1) and among non-bed net users was 2.6 iPPY (95% CI 2.0-3.3). Use of ITNs reduced the incidence of malaria infection by 30% (rate ratio 0.7;95% CI, 0.5-0.8) compared to no bed nets. Conclusion: ITNs significantly reduced the incidence of malaria infection in children in an area with moderate evels of pyrethroid resistance and considerable malaria transmission. This is the first study to show that ITNs provide protection in areas where pyrethroid-resistant An. funestus is the major malaria vector. Malaria control programmes should continue to distribute and promote ITNs in areas with low to moderate pyrethroid resistance; however, insecticide resistance may intensify further and it is not known whether ITNs will remain effective at higher levels of resistance. There is an urgent need to identify or develop new insecticides and technologies to limit the vulnerability of ITNs to insecticide resistance. © 2015 Lindblade et al.; licensee BioMed Central.

Steinhardt L.C.,Centers for Disease Control and Prevention | Chinkhumba J.,Malaria Alert Center | Wolkon A.,Centers for Disease Control and Prevention | Luka M.,Malaria Alert Center | And 6 more authors.
Malaria Journal | Year: 2014

Background: Prompt and effective case management is needed to reduce malaria morbidity and mortality. However, malaria diagnosis and treatment is a multistep process that remains problematic in many settings, resulting in missed opportunities for effective treatment as well as overtreatment of patients without malaria. Methods. Prior to the widespread roll-out of malaria rapid diagnostic tests (RDTs) in late 2011, a national, cross-sectional, complex-sample, health facility survey was conducted in Malawi to assess patient-, health worker-, and health facility-level factors associated with malaria case management quality using multivariate Poisson regression models. Results: Among the 2,019 patients surveyed, 34% had confirmed malaria defined as presence of fever and parasitaemia on a reference blood smear. Sixty-seven per cent of patients with confirmed malaria were correctly prescribed the first-line anti-malarial, with most cases of incorrect treatment due to missed diagnosis; 31% of patients without confirmed malaria were overtreated with an anti-malarial. More than one-quarter of patients were not assessed for fever or history of fever by health workers. The most important determinants of correct malaria case management were patient-level clinical symptoms, such as spontaneous complaint of fever to health workers, which increased both correct treatment and overtreatment by 72 and 210%, respectively (p < 0.0001). Complaint of cough was associated with a 27% decreased likelihood of correct malaria treatment (p = 0.001). Lower-level cadres of health workers were more likely to prescribe anti-malarials for patients, increasing the likelihood of both correct treatment and overtreatment, but no other health worker or health facility-level factors were significantly associated with case management quality. Conclusions: Introduction of RDTs holds potential to improve malaria case management in Malawi, but health workers must systematically assess all patients for fever, and then test and treat accordingly, otherwise, malaria control programmes might miss an opportunity to dramatically improve malaria case management, despite better diagnostic tools. © 2014 Steinhardt et al.; licensee BioMed Central Ltd.

Stanton M.C.,Center for Neglected Tropical Diseases | Mkwanda S.,Ministry of Health | Mzilahowa T.,Malaria Alert Center | Bockarie M.J.,Center for Neglected Tropical Diseases | Kelly-Hope L.A.,Center for Neglected Tropical Diseases
Tropical Medicine and International Health | Year: 2014

Objective: To quantify the geographical extent of filariasis and malaria control interventions impacting lymphatic filariasis (LF) in Malawi and to produce a multiple intervention score map (MISM) for prioritising surveillance and intervention strategies. Methods: Interventions included mass drug administration (MDA) for LF and onchocerciasis, and bed nets and indoor residual spraying (IRS) for malaria. District and subdistrict-level data were obtained from the Ministry of Health in Malawi, the Demographic and Health Survey (DHS) and President's Malaria Initiative reports. Single intervention scores were calculated for each variable based on population coverage thresholds, and these were combined in a weighted sum to form a multiple intervention score, which was then used to produce maps, that is MISMs. Districts were further classified into four groups based on the combination of their baseline LF prevalence and multiple intervention score. Results: The district- and subdistrict-level MISMs highlighted specific areas that have received high and low coverage of LF-impacting interventions. High coverage areas included the LF-onchocerciasis endemic areas in the southern region of the country and areas along the shores of Lake Malawi, where malaria vector control had been prioritised. Three districts with high baseline LF prevalence measures but low coverage of multiple interventions were identified and considered to be most at risk of ongoing transmission or re-emergence. Conclusions: These maps and district classifications will be used by LF programme managers to identify and target high-risk areas that may not have received adequate LF-impacting interventions to interrupt the transmission of the disease. © 2014 John Wiley & Sons Ltd.

PubMed | Malaria Vector Control Consultant, Malaria Alert Center, World Health Organization, Ministry of Health and Centers for Disease Control and Prevention
Type: Journal Article | Journal: Bulletin of the World Health Organization | Year: 2016

Indoor residual spraying and long-lasting insecticidal nets (LLINs) are key tools for malaria vector control. Malawi has struggled to scale up indoor residual spraying and to improve LLIN coverage and usage.In 2002, the Malawian National Malaria Control Programme developed guidelines for insecticide treated net distribution to reach the strategic target of at least 60% coverage of households with an LLIN. By 2005, the target coverage was 80% of households and the Global Fund financed the scale-up. The US Presidents Malaria Initiative funded the indoor residual spraying intervention.Malawis entire population is considered to be at risk of malaria. Poor vector control, insecticide resistance in malaria vectors and insufficient technical and financial support have exacerbated the malaria burden.Between 2002 and 2012, 18248206 LLINs had been distributed. The coverage of at least one LLIN per household increased from 27% (3689/13664) to 58% (1974/3404). Indoor residual spraying coverage increased from 28227 to 653592 structures between 2007 and 2011. However, vector resistance prompted a switch from pyrethroids to organophosphates for indoor residual spraying, which increased the cost and operations needed to be cut back from seven to one district. Malaria cases increased from 2853315 in 2002 to 6748535 in 2010, and thereafter dropped to 4922596 in 2012.A single intervention-based approach for vector control may have suboptimal impact. Well-coordinated integrated vector management may offer greater benefits. A resistance management plan is essential for effective and sustainable vector control.

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