ResearchPad - malaria https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[A twenty-eight-year laboratory-based retrospective trend analysis of malaria in Dakar, Senegal]]> https://www.researchpad.co/article/elastic_article_14736 Health facility-based records offer a rich source of information to understand trends and changes in malaria cases over time. This study is aimed at determining the changes in malaria occurrence over the last 28 years, from 1989 to 2016 in Dakar, Senegal.MethodsLaboratory suspected and confirmed malaria records from 1989 to 2016 were reviewed from the laboratory registers of the Laboratory of Parasitology and Mycology of Aristide Le Dantec Hospital. Interrupted time series (ITS) analysis was used to estimate the changes by comparing malaria cases post-intervention (2006–2016) with that of the pre-intervention (1989–2005) period.ResultsA total of 5,876 laboratory confirmed malaria cases were reported out of 29,852 tested cases, with total slide positivity rate (SPR) of 19.7%. Malaria case counts exhibited a fluctuating trend with major peaks occurring in the years 1995 and 2003 with SPR of 42.3% and 42.5%, respectively. Overall, a remarkable decline in the total number of laboratory confirmed malaria cases was observed over the last 28 years. P. falciparum was almost the only reported species, accounting for 99.98% of cases. The highest SPR was observed in the age group of under five years during the pre-intervention period while this shifted to the age group of 6–15 years old for the subsequent years. Two major malaria peak seasons were observed: one in September during the pre-intervention period and the other in November for the post-intervention period. The ITS analysis showed a dramatic decline of 83.6% in SPR following the scale-up of interventions in 2006.ConclusionA remarkable decline in laboratory confirmed malaria cases in Dakar over 28 years was observed. The period of rapid decline in malaria SPR coincided with the scale-up in interventions beginning in 2006 with the introduction of ACTs, followed by the widespread introduction in 2008 of bed nets treated with insecticides. Robust surveillance data should be maintained in the context of malaria elimination efforts. ]]> <![CDATA[Indoor and outdoor residual spraying of a novel formulation of deltamethrin K-Othrine<sup>®</sup> (Polyzone) for the control of simian malaria in Sabah, Malaysia]]> https://www.researchpad.co/article/elastic_article_14704 Since 2000, human malaria cases in Malaysia were rapidly reduced with the use of insecticides in Indoor Residual Spray (IRS) and Long-Lasting Insecticide Net (LLIN). Unfortunately, monkey malaria in humans has shown an increase especially in Sabah and Sarawak. The insecticide currently used in IRS is deltamethrin K-Othrine® WG 250 wettable granule, targeting mosquitoes that rest and feed indoor. In Sabah, the primary vector for knowlesi malaria is An. balabacensis a species known to bite outdoor. This study evaluates an alternative method, the Outdoor Residual Spray (ORS) using a novel formulation of deltamethrin K-Othrine® (PolyZone) to examine it suitability to control knowlesi malaria vector in Sabah, compared to the current method. The study was performed at seven villages in Sabah having similar type of houses (wood, bamboo and concrete). Houses were sprayed with deltamethrin K-Othrine® (PolyZone) at two different dosages, 25 mg/m2 and 30 mg/m2 and deltamethrin K-Othrine® WG 250 wettable granule at 25 mg/m2, sprayed indoor and outdoor. Residual activity on different walls was assessed using standard cone bioassay techniques. For larval surveillances, potential breeding sites were surveyed. Larvae were collected and identified, pre and post spraying. Adult survey was done using Human Landing Catch (HLC) performed outdoor and indoor. Detection of malaria parasite in adults was conducted via microscopy and molecular methods. Deltamethrin K-Othrine® (PolyZone) showed higher efficacy when sprayed outdoor. The efficacy was found varied when sprayed on different types of wall surfaces. Deltamethrin K-Othrine® (PolyZone) at 25 mg/m2 was the most effective with regards to ability to high mortality and effective knock down (KD). The vector population was reduced significantly post-spraying and reduction in breeding sites as well. The number of simian malaria infected vector, human and simian malaria transmission were also greatly reduced.

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<![CDATA[Cytokine signatures of <i>Plasmodium vivax</i> infection during pregnancy and delivery outcomes]]> https://www.researchpad.co/article/elastic_article_14648 Cytokine and growth factor plasma concentrations were evaluated in women from five countries endemic for malaria vivax, at different moments and blood compartments during pregnancy. P. vivax infection during pregnancy was associated with a pro-inflammatory and TH1 response, together with an antiinflammatory response. Nevertheless, at delivery most associations between cytokines and infection were lost. Of note, CCL11/eotaxin, a chemokine not generally analyzed in malaria studies, presented a lower concentration in P. vivax-infected women and a protective association with hemoglobin levels at delivery. Moreover, IL-4 levels had a negative association with birth weight. Data suggest that a compensated inflammatory/antiinflammatory response in P. vivax infection during pregnancy might avoid poor delivery outcomes, while a predominance of TH2 responses may be detrimental for birth weight. Further research is warranted to unravel the role of CCL11 in malaria infection or exposure.

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<![CDATA[Correlates of childhood morbidity in Nigeria: Evidence from ordinal analysis of cross-sectional data]]> https://www.researchpad.co/article/elastic_article_14636 Child mortality records show that 1 in every 13 children dies before age five in sub-Saharan Africa with diseases such as pneumonia, diarrhoea and malaria considered to be the leading causes of such deaths. In Nigeria where 50% of all under-five deaths are attributed to morbidity, much attention has been directed to single health conditions. This study aims at examining the factors that are associated with single health conditions and comorbidity among children in Nigeria.Materials and methodsThis study was based on data from 2013 Nigeria Demographic and Health Survey (DHS) which involved 27,571 under-five children who suffered from acute respiratory infection, diarrhoea or fever within two weeks of data collection exercise. Descriptive statistics and generalized ordinal logistic regression model were used for the analysis.ResultsAbout 14% of children suffered from a single health condition and 9% suffered from comorbidity. The likelihood of suffering from a single health condition and comorbidity is higher for children who are of third order birth or more (OR = 1.24, 95% CI = 1.11–1.39 & OR = 1.31, 95% CI = 1.12–1.55) compared to those who are of first order birth. The likelihood also increased for children whose mothers live in Northeast (OR = 3.19, 95% CI = 2.86–3.55 & OR = 3.88, 95% CI = 3.30–4.57) compared to children whose mothers live in North Central. The odds of suffering from a single health condition and comorbidity reduced for children who are from richest households, aged 3 years and above and were of average size at birth. Children of women who obtained water from improved source are less likely to experience any morbidity (OR = 0.93, 95% CI = 0.87–0.99) compared to children whose mothers obtained water from non-improved source.ConclusionsThe study has demonstrated that children in Nigeria are not only exposed to the risk of single health conditions but they are also exposed to the risk of comorbidity. Efforts should be made to design appropriate health care models that would facilitate a considerable reduction in childhood morbidity in the country. ]]> <![CDATA[Quantification of glucose-6-phosphate dehydrogenase activity by spectrophotometry: A systematic review and meta-analysis]]> https://www.researchpad.co/article/elastic_article_14551 Complete cure of vivax malaria, the most geographically widespread malaria species, requires the use of 8-aminoquinoline drugs to clear dormant liver stages of the parasite (‘radical cure’); however, these drugs can cause severe haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency.Ultraviolet (UV) spectrophotometry is used as the reference test to measure G6PD activity, for validating new point-of-care diagnostics, and to determine population-specific definitions of G6PD deficiency.Currently, there is no universal threshold to define G6PD deficiency, and each laboratory must invest time and resources to derive site- and laboratory-specific definitions of G6PD deficiency.What did the researchers do and find?We pooled measurements of G6PD activity from studies conducted across different countries and laboratories worldwide.We assessed the comparability of spectrophotometry results between these laboratories to see whether a universal definition and diagnostic cutoff for G6PD deficiency could be determined.There was substantial variation in the performance and absolute measurements of spectrophotometry conducted in different laboratories, hindering the definition of a universal cutoff for G6PD deficiency.What do these findings mean?These findings highlight the importance of quality-control measures to minimise the influence of laboratory procedures on observed measurements.The data suggest that while a robust universal, assay-specific G6PD activity cutoff value can be established for diagnosis of severe G6PD deficiency (<30% normal enzyme activity), this approach is less robust for diagnosing intermediate G6PD deficiency.Newly developed diagnostic assays that are less sensitive to laboratory conditions and require less sample preparation are required and may help provide more standardised quantitative G6PD activity measurements across different contexts. ]]> <![CDATA[Exposure to Ebola Virus and Risk for Infection with Malaria Parasites, Rural Gabon ]]> https://www.researchpad.co/article/N28cdc5e0-b3fc-45d9-a0f2-dff11ae2b038

An association between malaria and risk for death among patients with Ebola virus disease has suggested within-host interactions between Plasmodium falciparum parasites and Ebola virus. To determine whether such an interaction might also influence the probability of acquiring either infection, we used a large snapshot surveillance study from rural Gabon to test if past exposure to Ebola virus is associated with current infection with Plasmodium spp. during nonepidemic conditions. We found a strong positive association, on population and individual levels, between seropositivity for antibodies against Ebola virus and the presence of Plasmodium parasites in the blood. According to a multiple regression model accounting for other key variables, antibodies against Ebola virus emerged as the strongest individual-level risk factor for acquiring malaria. Our results suggest that within-host interactions between malaria parasites and Ebola virus may underlie epidemiologic associations.

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<![CDATA[A mathematical model for assessing the effectiveness of controlling relapse in Plasmodium vivax malaria endemic in the Republic of Korea]]> https://www.researchpad.co/article/Nf3d8dda1-10e2-4286-9776-07d534017a03

Malaria has persisted as an endemic near the Demilitarized Zone in the Republic of Korea since the re-emergence of Plasmodium vivax malaria in 1993. The number of patients affected by malaria has increased recently despite many controls tools, one of the reasons behind which is the relapse of malaria via liver hypnozoites. Tafenoquine, a new drug approved by the United States Food and Drug Administration in 2018, is expected to reduce the rate of relapse of malaria hypnozoites and thereby decrease the prevalence of malaria among the population. In this work, we have developed a new transmission model for Plasmodium vivax that takes into account a more realistic intrinsic distribution from existing literature to quantify the current values of relapse parameters and to evaluate the effectiveness of the anti-relapse therapy. The model is especially suitable for estimating parameters near the Demilitarized Zone in Korea, in which the disease follows a distinguishable seasonality. Results were shown that radical cure could significantly reduce the prevalence level of malaria. However, eradication would still take a long time (over 10 years) even if the high-level treatment were to persist. In addition, considering that the vector’s behavior is manipulated by the malaria parasite, relapse repression through vector control at the current level may result in a negative effect in containing the disease. We conclude that the use of effective drugs should be considered together with the increased level of the vector control to reduce malaria prevalence.

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<![CDATA[Behavior and abundance of Anopheles darlingi in communities living in the Colombian Amazon riverside]]> https://www.researchpad.co/article/5c8acc3ed5eed0c48498f2cc

In the past few years, relative frequencies of malaria parasite species in communities living in the Colombian Amazon riverside have changed, being Plasmodium vivax (61.4%) and Plasmodium malariae (43.8%) the most frequent. Given this epidemiological scenario, it is important to determine the species of anophelines involved in these parasites’ transmission. This study was carried out in June 2016 in two indigenous communities living close to the tributaries of the Amazon River using protected human bait. The results of this study showed a total abundance of 1,085 mosquitos, of which 99.2% corresponded to Anopheles darlingi. Additionally, only two anopheline species were found, showing low diversity in the study areas. Molecular confirmation of some individuals was then followed by evolutionary analysis by using the COI gene. Nested PCR was used for identifying the three Plasmodium species circulating in the study areas. Of the two species collected in this study, 21.0% of the An. darlingi mosquitoes were infected with P. malariae, 21.9% with P. vivax and 10.3% with Plasmodium falciparum. It exhibited exophilic and exophagic behavior in both study areas, having marked differences regarding its abundance in each community (Tipisca first sampling 49.4%, Tipisca second sampling 39.6% and Doce de Octubre 10.9%). Interestingly, An. mattogrossensis infected by P. vivax was found for the first time in Colombia (in 50% of the four females collected). Analysis of An. darlingi COI gene diversity indicated a single population maintaining a high gene flow between the study areas. The An. darlingi behavior pattern found in both communities represents a risk factor for the region’s inhabitants living/working near these sites. This highlights the need for vector control efforts such as the use of personal repellents and insecticides for use on cattle, which must be made available in order to reduce this Anopheline’s abundance.

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<![CDATA[Citrulline protects mice from experimental cerebral malaria by ameliorating hypoargininemia, urea cycle changes and vascular leak]]> https://www.researchpad.co/article/5c8c194bd5eed0c484b4d370

Clinical and model studies indicate that low nitric oxide (NO) bioavailability due in part to profound hypoargininemia contributes to cerebral malaria (CM) pathogenesis. Protection against CM pathogenesis may be achieved by altering the diet before infection with Plasmodium falciparum infection (nutraceutical) or by administering adjunctive therapy that decreases CM mortality (adjunctive therapy). This hypothesis was tested by administering citrulline or arginine in experimental CM (eCM). We report that citrulline injected as prophylaxis immediately post infection (PI) protected virtually all mice by ameliorating (i) hypoargininemia, (ii) urea cycle impairment, and (iii) disruption of blood brain barrier. Citrulline prophylaxis inhibited plasma arginase activity. Parasitemia was similar in citrulline- and vehicle control-groups, indicating that protection from pathogenesis was not due to decreased parasitemia. Both citrulline and arginine administered from day 1 PI in the drinking water significantly protected mice from eCM. These observations collectively indicate that increasing dietary citrulline or arginine decreases eCM mortality. Citrulline injected ip on day 4 PI with quinine-injected ip on day 6 PI partially protected mice from eCM; citrulline plus scavenging of superoxide with pegylated superoxide dismutase and pegylated catalase protected all recipients from eCM. These findings indicate that ameliorating hypoargininemia with citrulline plus superoxide scavenging decreases eCM mortality.

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<![CDATA[Antibody responses to Plasmodium vivax Duffy binding and Erythrocyte binding proteins predict risk of infection and are associated with protection from clinical Malaria]]> https://www.researchpad.co/article/5c706793d5eed0c4847c7266

Background

The Plasmodium vivax Duffy Binding Protein (PvDBP) is a key target of naturally acquired immunity. However, region II of PvDBP, which contains the receptor-binding site, is highly polymorphic. The natural acquisition of antibodies to different variants of PvDBP region II (PvDBPII), including the AH, O, P and Sal1 alleles, the central region III-V (PvDBPIII-V), and P. vivax Erythrocyte Binding Protein region II (PvEBPII) and their associations with risk of clinical P. vivax malaria are not well understood.

Methodology

Total IgG and IgG subclasses 1, 2, and 3 that recognize four alleles of PvDBPII (AH, O, P, and Sal1), PvDBPIII-V and PvEBPII were measured in samples collected from a cohort of 1 to 3 year old Papua New Guinean (PNG) children living in a highly endemic area of PNG. The levels of binding inhibitory antibodies (BIAbs) to PvDBPII (AH, O, and Sal1) were also tested in a subset of children. The association of presence of IgG with age, cumulative exposure (measured as the product of age and malaria infections during follow-up) and prospective risk of clinical malaria were evaluated.

Results

The increase in antigen-specific total IgG, IgG1, and IgG3 with age and cumulative exposure was only observed for PvDBPII AH and PvEBPII. High levels of total IgG and predominant subclass IgG3 specific for PvDBPII AH were associated with decreased incidence of clinical P. vivax episodes (aIRR = 0.56–0.68, P≤0.001–0.021). High levels of total IgG and IgG1 to PvEBPII correlated strongly with protection against clinical vivax malaria compared with IgGs against all PvDBPII variants (aIRR = 0.38, P<0.001). Antibodies to PvDBPII AH and PvEBPII showed evidence of an additive effect, with a joint protective association of 70%.

Conclusion

Antibodies to the key parasite invasion ligands PvDBPII and PvEBPII are good correlates of protection against P. vivax malaria in PNG. This further strengthens the rationale for inclusion of PvDBPII in a recombinant subunit vaccine for P. vivax malaria and highlights the need for further functional studies to determine the potential of PvEBPII as a component of a subunit vaccine for P. vivax malaria.

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<![CDATA[Algorithms for sequential interpretation of a malaria rapid diagnostic test detecting two different targets of Plasmodium species to improve diagnostic accuracy in a rural setting (Nanoro, Burkina Faso)]]> https://www.researchpad.co/article/5c6dc99fd5eed0c484529f2d

Background

Malaria rapid diagnostic tests (RDT) have limitations due to the persistence of histidine-rich protein 2 (HRP2) antigen after treatment and low sensitivity of Plasmodium lactate dehydrogenase (pLDH) based RDTs. To improve the diagnosis of malaria in febrile children, two diagnostic algorithms, based on sequential interpretation of a malaria rapid diagnostic test detecting two different targets of Plasmodium species and followed by expert microscopy, were evaluated.

Methods

Two diagnostic algorithms were evaluated using 407 blood samples collected between April and October 2016 from febrile children and the diagnostic accuracy of both algorithms was determined. Algorithm 1: The result of line T1-HRP2 were read first; if negative, malaria infection was considered to be absent. If positive, confirmation was done with the line T2-pLDH. If T2-pLDH test was negative, the malaria diagnosis was considered as “inconclusive” and microscopy was performed; Algorithm 2: The result of line T2-pLDH were read first; if positive, malaria infection was considered to be present. If negative, confirmation was done with the line T1-HRP2. If T1-HRP2 was positive the malaria diagnosis was considered as “inconclusive” and microscopy was performed. In absence of malaria microscopy, a malaria infection was ruled out in children with an inconclusive diagnostic test result when previous antimalarial treatment was reported.

Results

For single interpretation, the sensitivity of PfHRP2 was 98.4% and the specificity was 74.2%, and for the pLDH test the sensitivity was 89.3% and the specificity was 98.8%. Malaria was accurately diagnosed using both algorithms in 84.5% children. The algorithms with the two-line malaria RDT classified the test results into two groups: conclusive and inconclusive results. The diagnostic accuracy for conclusive results was 98.3% using diagnostic algorithm 1 and 98.6% using algorithm 2. The sensitivity and specificity for the conclusive results were 98.2% and 98.4% for algorithm 1, and 98.6% and 98.4% for algorithm 2, respectively. There were 63 (15.5%) children who had an “inconclusive” result for whom expert microscopy was needed. In children with inconclusive results (PfHRP2+/pLDH- only) previous antimalarial treatment was reported in 16 children with malaria negative microscopy (16/40; 40%) and 1 child with malaria positive microscopy (1/23; 4.3%).

Conclusion

The strategy of sequential interpretation of two-line malaria RDT can improve the diagnosis of malaria. However, some cases will still require confirmative testing with microscopy or additional investigations on previous antimalarial treatment.

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<![CDATA[Growing evidence of Plasmodium vivax across malaria-endemic Africa]]> https://www.researchpad.co/article/5c5ca2d6d5eed0c48441eb93

Effective malaria control strategies require an accurate understanding of the epidemiology of locally transmitted Plasmodium species. Compared to Plasmodium falciparum infection, Plasmodium vivax has a lower asexual parasitaemia, forms dormant liver-stages (hypnozoites), and is more transmissible. Hence, treatment and diagnostic policies aimed exclusively at P. falciparum are far less efficient against endemic P. vivax. Within sub-Saharan Africa, malaria control programmes justly focus on reducing the morbidity and mortality associated with P. falciparum. However, the recent emphasis on malaria elimination and increased accessibility of more sensitive diagnostic tools have revealed greater intricacies in malaria epidemiology across the continent. Since 2010, the number of studies identifying P. vivax endemic to Africa has expanded considerably, with 88 new scientific reports published since a review of evidence in 2015, approximately doubling the available data. There is evidence of P. vivax in all regions of Africa, apparent from infected vectors, clinical cases, serological indicators, parasite prevalence, exported infections, and P. vivax-infected Duffy-negative individuals. Where the prevalence of microscopic parasitaemia is low, a greater proportion of P. vivax infections were observed relative to P. falciparum. This evidence highlights an underlying widespread presence of P. vivax across all malaria-endemic regions of Africa, further complicating the current practical understanding of malaria epidemiology in this region. Thus, ultimate elimination of malaria in Africa will require national malaria control programmes to adopt policy and practice aimed at all human species of malaria.

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<![CDATA[The impact of targeted malaria elimination with mass drug administrations on falciparum malaria in Southeast Asia: A cluster randomised trial]]> https://www.researchpad.co/article/5c706743d5eed0c4847c6ce8

Background

The emergence and spread of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion (GMS) threatens global malaria elimination efforts. Mass drug administration (MDA), the presumptive antimalarial treatment of an entire population to clear the subclinical parasite reservoir, is a strategy to accelerate malaria elimination. We report a cluster randomised trial to assess the effectiveness of dihydroartemisinin-piperaquine (DP) MDA in reducing falciparum malaria incidence and prevalence in 16 remote village populations in Myanmar, Vietnam, Cambodia, and the Lao People’s Democratic Republic, where artemisinin resistance is prevalent.

Methods and findings

After establishing vector control and community-based case management and following intensive community engagement, we used restricted randomisation within village pairs to select 8 villages to receive early DP MDA and 8 villages as controls for 12 months, after which the control villages received deferred DP MDA. The MDA comprised 3 monthly rounds of 3 daily doses of DP and, except in Cambodia, a single low dose of primaquine. We conducted exhaustive cross-sectional surveys of the entire population of each village at quarterly intervals using ultrasensitive quantitative PCR to detect Plasmodium infections. The study was conducted between May 2013 and July 2017. The investigators randomised 16 villages that had a total of 8,445 residents at the start of the study. Of these 8,445 residents, 4,135 (49%) residents living in 8 villages, plus an additional 288 newcomers to the villages, were randomised to receive early MDA; 3,790 out of the 4,423 (86%) participated in at least 1 MDA round, and 2,520 out of the 4,423 (57%) participated in all 3 rounds. The primary outcome, P. falciparum prevalence by month 3 (M3), fell by 92% (from 5.1% [171/3,340] to 0.4% [12/2,828]) in early MDA villages and by 29% (from 7.2% [246/3,405] to 5.1% [155/3,057]) in control villages. Over the following 9 months, the P. falciparum prevalence increased to 3.3% (96/2,881) in early MDA villages and to 6.1% (128/2,101) in control villages (adjusted incidence rate ratio 0.41 [95% CI 0.20 to 0.84]; p = 0.015). Individual protection was proportional to the number of completed MDA rounds. Of 221 participants with subclinical P. falciparum infections who participated in MDA and could be followed up, 207 (94%) cleared their infections, including 9 of 10 with artemisinin- and piperaquine-resistant infections. The DP MDAs were well tolerated; 6 severe adverse events were detected during the follow-up period, but none was attributable to the intervention.

Conclusions

Added to community-based basic malaria control measures, 3 monthly rounds of DP MDA reduced the incidence and prevalence of falciparum malaria over a 1-year period in areas affected by artemisinin resistance. P. falciparum infections returned during the follow-up period as the remaining infections spread and malaria was reintroduced from surrounding areas. Limitations of this study include a relatively small sample of villages, heterogeneity between villages, and mobility of villagers that may have limited the impact of the intervention. These results suggest that, if used as part of a comprehensive, well-organised, and well-resourced elimination programme, DP MDA can be a useful additional tool to accelerate malaria elimination.

Trial registration

ClinicalTrials.gov NCT01872702

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<![CDATA[Community health workers trained to conduct verbal autopsies provide better mortality measures than existing surveillance: Results from a cross-sectional study in rural western Uganda]]> https://www.researchpad.co/article/5c6dca23d5eed0c48452a833

Background

In much of sub-Saharan Africa, health facilities serve as the primary source of routine vital statistics. These passive surveillance systems, however, are plagued by infrequent and unreliable reporting and do not capture events that occur outside of the formal health sector. Verbal autopsies (VA) have been utilized to estimate the burden and causes of mortality where civil registration and vital statistics systems are weak, but VAs have not been widely employed in national surveillance systems. In response, we trained lay community health workers (CHW) in a rural sub-county of western Uganda to conduct VA interviews in order to assess the feasibility of leveraging CHW to measure the burden of disease in resource limited settings.

Methods and findings

Trained CHWs conducted a cross-sectional survey of the 36 villages comprising the Bugoye sub-county to identify all deaths occurring in the prior year. The sub county has an estimated population of 50,249, approximately one-quarter of whom are children under 5 years of age (25.3%). When an eligible death was reported, CHWs administered a WHO 2014 VA questionnaire, the results of which were analyzed using the InterVA-4 tool. To compare the findings of the CHW survey to existing surveillance systems, study staff reviewed inpatient registers from neighboring referral health facilities in an attempt to match recorded deaths to those identified by the survey. Overall, CHWs conducted high quality VA interviews on direct observation, identifying 230 deaths that occurred within the sub-county, including 77 (33.5%) among children under five years of age. More than half of the deaths (123 of 230, 53.5%) were reported to have occurred outside a health facility and thus would not be captured by passive surveillance. More than two-thirds (73 of 107, 68.2%) of facility deaths took place in one of three nearby hospitals, yet only 35 (47.9%) were identified on our review of inpatient registers. Consistent with previous VA studies, the leading causes of death among children under five years of age were malaria (19.5%), prematurity (19.5%), and neonatal pneumonia (15.6%). while among adults, HIV/AIDS-related deaths illness (13.6%), pulmonary tuberculosis (11.4%) and malaria (8.6%) were the leading causes of death. No child deaths identified from inpatient registers listed HIV/AIDS as a cause of death despite 8 deaths (10.4%) attributed to HIV/AIDS as determined by VA.

Conclusions

Lay CHWs are able to conduct high quality VA interviews to capture critical information that can be analyzed using standard methodologies to provide a more complete estimate of the burden and causes of mortality. Similar approaches can be scaled to improve the measurement of vital statistics in order to facilitate appropriate public health interventions in rural areas of sub-Saharan Africa.

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<![CDATA[Spatial and temporal development of deltamethrin resistance in malaria vectors of the Anopheles gambiae complex from North Cameroon]]> https://www.researchpad.co/article/5c75ac7cd5eed0c484d088a5

The effectiveness of insecticide-based malaria vector control interventions in Africa is threatened by the spread and intensification of pyrethroid resistance in targeted mosquito populations. The present study aimed at investigating the temporal and spatial dynamics of deltamethrin resistance in An. gambiae s.l. populations from North Cameroon. Mosquito larvae were collected from 24 settings of the Garoua, Pitoa and Mayo Oulo Health Districts (HDs) from 2011 to 2015. Two to five days old female An. gambiae s.l. emerging from larval collections were tested for deltamethrin resistance using the World Health Organization’s (WHO) standard protocol. Sub samples of test mosquitoes were identified to species using PCR-RFLP and genotyped for knockdown resistance alleles (Kdr 1014F and 1014S) using Hot Ligation Oligonucleotide Assay (HOLA). All the tested mosquitoes were identified as belonging to the An. gambiae complex, including 3 sibling species mostly represented by Anopheles arabiensis (67.6%), followed by Anopheles coluzzii (25.4%) and Anopheles gambiae (7%). Deltamethrin resistance frequencies increased significantly between 2011 and 2015, with mosquito mortality rates declining from 70–85% to 49–73% in the three HDs (Jonckheere-Terstra test statistic (JT) = 5638, P< 0.001), although a temporary increase of mortality rates (91–97%) was seen in the Pitoa and Mayo Oulo HDs in 2012. Overall, confirmed resistance emerged in 10 An. gambiae s.l. populations over the 24 field populations monitored during the study period, from 2011 to 2015. Phenotypic resistance was mostly found in urban settings compared with semi-urban and rural settings (JT = 5282, P< 0.0001), with a spatial autocorrelation between neighboring localities. The Kdr 1014F allelic frequencies in study HDs increased from 0–30% in 2011 to 18–61% in 2014–2015 (JT = 620, P <0.001), especially in An. coluzzii samples. The overall frequency of the Kdr 1014S allele was 0.1%. This study revealed a rapid increase and widespread deltamethrin resistance frequency as well as Kdr 1014F allelic frequencies in An. gambiae s.l. populations over time, emphasizing the urgent need for vector surveillance and insecticide resistance management strategies in Cameroon.

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<![CDATA[Prevalence of malaria and hepatitis B among pregnant women in Northern Ghana: Comparing RDTs with PCR]]> https://www.researchpad.co/article/5c648d4fd5eed0c484c8250b

Background

High prevalence of malaria and hepatitis B has been reported among pregnant women in Ghana. In endemic areas, the diagnoses of malaria and hepatitis B among pregnant women on antenatal visits are done using histidine-rich protein 2 (HRP2) and hepatitis B surface antigen (HBsAg) rapid diagnostic tests (RDTs), respectively, which are, however, reported to give some false positive results. Also, socio-economic determinants have been drawn from these RDTs results which may have questionable implications. Thus, this study was aimed at evaluating the prevalence of malaria and hepatitis B by comparing RDTs with polymerase chain reaction (PCR) outcomes, and relating the PCR prevalence with socio-economic status among pregnant women in Northern Ghana.

Methods

We screened 2071 pregnant women on their first antenatal visit for Plasmodium falciparum and hepatitis B virus (HBV) using HRP2 and HBsAg RDTs, and confirming the infections with PCR. Socio-economic and obstetric information were collected using a pre-tested questionnaire, and associations with the infections were determined using Pearson’s chi-square and multinomial logistic regression analyses at a significance level of p<0.05.

Results

The prevalence of the infections by RDTs/PCR was: 14.1%/13.4% for P. falciparum mono-infection, 7.9%/7.5% for HBV mono-infection, and 1.9%/1.7% for P. falciparum/HBV co-infection. No statistical difference in prevalence rates were observed between the RDTs and PCRs (χ2  =  0.119, p = 0.73 for malaria and χ2  =  0.139, p = 0.709 for hepatitis B). Compared with PCRs, the sensitivity/specificity of the RDTs was 97.5%/99.1% and 97.9%/99.4% for HRP2 and HBsAg respectively. Socio-economic status was observed not to influence HBV mono-infection among the pregnant women (educational status: AOR = 0.78, 95% CI = 0.52–1.16, p = 0.222; economic status: AOR = 1.07, 95% CI = 0.72–1.56, p = 0.739; financial status: AOR = 0.66, 95% CI = 0.44–1.00, p = 0.052). However, pregnant women with formal education were at a lower risk for P. falciparum mono-infection (AOR = 0.48, 95% CI  =  0.32–0.71, p<0.001) and P. falciparum/HBV co-infection (AOR = 0.27, 95% CI  =  0.11–0.67, p = 0.005). Also those with good financial status were also at a lower risk for P. falciparum mono-infection (AOR = 0.52, 95% CI  =  0.36–0.74, p<0.001).

Conclusion

Our data has shown that, the RDTs are comparable to PCR and can give a representative picture of the prevalence of malaria and hepatitis B in endemic countries. Also, our results support the facts that improving socio-economic status is paramount in eliminating malaria in endemic settings. However, socio-economic status did not influence the prevalence of HBV mono-infection among pregnant women in Northern Ghana.

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<![CDATA[Predicting the direct and indirect impacts of climate change on malaria in coastal Kenya]]> https://www.researchpad.co/article/5c648cdfd5eed0c484c819a9

Background

The transmission of malaria is highly variable and depends on a range of climatic and anthropogenic factors. This study investigates the combined, i.e. direct and indirect, impacts of climate change on the dynamics of malaria through modifications in: (i) the sporogonic cycle of Plasmodium induced by air temperature increase, and (ii) the life cycle of Anopheles vector triggered by changes in natural breeding habitat arising from the altered moisture dynamics resulting from acclimation responses of vegetation under climate change. The study is performed for a rural region in Kilifi county, Kenya.

Methods and findings

We use a stochastic lattice-based malaria (SLIM) model to make predictions of changes in Anopheles vector abundance, the life cycle of Plasmodium parasites, and thus malaria transmission under projected climate change in the study region. SLIM incorporates a nonlinear temperature-dependence of malaria parasite development to estimate the extrinsic incubation period of Plasmodium. It is also linked with a spatially distributed eco-hydrologic modeling framework to capture the impacts of climate change on soil moisture dynamics, which served as a key determinant for the formation and persistence of mosquito larval habitats on the land surface. Malaria incidence data collected from 2008 to 2013 is used for SLIM model validation. Projections of climate change and human population for the region are used to run the models for prediction scenarios.

Under elevated atmospheric CO2 concentration ([CO2]) only, modeled results reveal wetter soil moisture in the root zone due to the suppression of transpiration from vegetation acclimation, which increases the abundance of Anopheles vectors and the risk of malaria. When air temperature increases are also considered along with elevated [CO2], the life cycle of Anopheles vector and the extrinsic incubation period of Plasmodium parasites are shortened nonlinearly. However, the reduction of soil moisture resulting from higher evapotranspiration due to air temperature increase also reduces the larval habitats of the vector. Our findings show the complicated role of vegetation acclimation under elevated [CO2] on malaria dynamics and indicate an indirect but ignored impact of air temperature increase on malaria transmission through reduction in larval habitats and vector density.

Conclusions

Vegetation acclimation triggered by elevated [CO2] under climate change increases the risk of malaria. In addition, air temperature increase under climate change has opposing effects on mosquito larval habitats and the life cycles of both Anopheles vectors and Plasmodium parasites. The indirect impacts of temperature change on soil moisture dynamics are significant and should be weighed together with the direct effects of temperature change on the life cycles of mosquitoes and parasites for future malaria prediction and control.

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<![CDATA[High-accuracy detection of malaria vector larval habitats using drone-based multispectral imagery]]> https://www.researchpad.co/article/5c4a305cd5eed0c4844bfe34

Interest in larval source management (LSM) as an adjunct intervention to control and eliminate malaria transmission has recently increased mainly because long-lasting insecticidal nets (LLINs) and indoor residual spray (IRS) are ineffective against exophagic and exophilic mosquitoes. In Amazonian Peru, the identification of the most productive, positive water bodies would increase the impact of targeted mosquito control on aquatic life stages. The present study explores the use of unmanned aerial vehicles (drones) for identifying Nyssorhynchus darlingi (formerly Anopheles darlingi) breeding sites with high-resolution imagery (~0.02m/pixel) and their multispectral profile in Amazonian Peru. Our results show that high-resolution multispectral imagery can discriminate a profile of water bodies where Ny. darlingi is most likely to breed (overall accuracy 86.73%- 96.98%) with a moderate differentiation of spectral bands. This work provides proof-of-concept of the use of high-resolution images to detect malaria vector breeding sites in Amazonian Peru and such innovative methodology could be crucial for LSM malaria integrated interventions.

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<![CDATA[Contrasting patterns of gene expression indicate differing pyrethroid resistance mechanisms across the range of the New World malaria vector Anopheles albimanus]]> https://www.researchpad.co/article/5c5b5298d5eed0c4842bcc50

Decades of unmanaged insecticide use and routine exposure to agrochemicals have left many populations of malaria vectors in the Americas resistant to multiple classes of insecticides, including pyrethroids. The molecular basis of pyrethroid resistance is relatively uncharacterised in American malaria vectors, preventing the design of suitable resistance management strategies. Using whole transcriptome sequencing, we characterized the mechanisms of pyrethroid resistance in Anopheles albimanus from Peru and Guatemala. An. albimanus were phenotyped as either deltamethrin or alpha-cypermethrin resistant. RNA from 1) resistant, 2) unexposed, and 3) a susceptible laboratory strain of An. albimanus was sequenced and analyzed using RNA-Seq. Expression profiles of the three groups were compared based on the current annotation of the An. albimanus reference genome. Several candidate genes associated with pyrethroid resistance in other malaria vectors were found to be overexpressed in resistant An. albimanus. In addition, gene ontology terms related to serine-type endopeptidase activity, extracellular activity and chitin metabolic process were also commonly overexpressed in the field caught resistant and unexposed samples from both Peru and Guatemala when compared to the susceptible strain. The cytochrome P450 CYP9K1 was overexpressed 14x in deltamethrin and 8x in alpha-cypermethrin-resistant samples from Peru and 2x in deltamethrin-resistant samples from Guatemala, relative to the susceptible laboratory strain. CYP6P5 was overexpressed 68x in deltamethrin-resistant samples from Peru but not in deltamethrin-resistant samples from Guatemala. When comparing overexpressed genes between deltamethrin-resistant and alpha-cypermethrin-resistant samples from Peru, a single P450 gene, CYP4C26, was overexpressed 9.8x (p<0.05) in alpha-cypermethrin-resistant samples. In Peruvian deltamethrin-resistant samples, the knockdown resistance mutation (kdr) variant alleles at position 1014 were rare, with approximately 5% frequency, but in the alpha-cypermethrin-resistant samples, the frequency of these alleles was approximately 15–30%. Functional validation of the candidate genes and the kdr mutation as a resistance marker for alpha-cypermethrin will confirm the role of these mechanisms in conferring pyrethroid resistance.

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<![CDATA[Socio-economic and demographic disparities in ownership and use of insecticide-treated bed nets for preventing malaria among rural reproductive-aged women in northern Ghana]]> https://www.researchpad.co/article/5c59fed1d5eed0c48413562d

Background

Malaria continues to be a leading cause of morbidity and mortality in most countries in Sub-Saharan Africa. Insecticide-treated bed nets (ITNs) is one of the cost-effective interventions for preventing malaria in endemic settings. Ghana has made tremendous efforts to ensure widespread ownership and use of ITNs. However, national coverage statistics can mask important inequities that demand targeted attention. This study assesses the disparities in ownership and utilization of ITNs among reproductive-aged women in a rural impoverished setting of Ghana.

Methods

Population-based cross-sectional data of 3,993 women between the age of 15 and 49 years were collected in seven districts of the Upper East region of Ghana using a two-stage cluster sampling approach. Bivariate and multivariate regression models were used to assess the social, economic and demographic disparities in ownership and utilization of ITN and to compare utilization rates among women in households owning at least one ITN.

Results

As high as 79% of respondents were found to own ITN while 62% of ITN owners used them the night preceding the survey. We identified disparities in both ownership and utilization of ITNs in wealth index, occupational status, religion, and district of residence. Respondents in the relative richest wealth quintile were 74% more likely to own ITNs compared to those in the poorest quintile (p-value< 0.001, CI = 1.29–2.34) however, they were 33% less likely to use ITNs compared to the poorest (p-value = 0.01, CI = 0.50–0.91).

Conclusion

Interventions aimed at preventing and controlling malaria through the use of bed nets in rural Ghana and other similar settings should give more attention to disadvantage populations such as the poor and unemployed. Tailored massages and educational campaigns are required to ensure consistent use of treated bed nets.

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