Malaria elimination in Ghana: recommendations for reactive case detection strategy implementation in a low endemic area of Asutsuare, Ghana.

BACKGROUND: Progress toward malaria elimination is increasing as many countries near zero indigenous malaria cases. In settings nearing elimination, interventions will be most effective at interrupting transmission when targeted at the residual foci of transmission. These foci may be missed due to asymptomatic infections. To solve this problem, the World Health Organization recommends reactive case detection (RACD). This case study was conducted to identify individuals with asymptomatic malaria, their predisposing risk factors and recommend RACD in Asutsuare, Ghana based on literature review and a cross sectional study. METHODS: The study involved a search on PubMed and Google Scholar of literature published between 1st January, 2009-14th August, 2023 using the search terms "malaria" in "Asutsuare". Furthermore, structured questionnaires were administered to one hundred individuals without symptoms of malaria and screened using rapid diagnostic test (RDT) kits, microscopy and real-time polymerase chain reaction (rt-PCR). Malaria prevalence based on the three diagnostic techniques as well as potential malaria risk factors were assessed through questionnaires in a cross-sectional study. RESULTS: Cumulatively, sixty-four (64) studies (Google Scholar, 57 and PubMed, 7) were reviewed and 22 studies included in the literature on malaria in Asutsuare, Ghana. Significant risk factors were occupation, distance from a house to a waterbody, age group and educational level. Out of the 100 samples, 3 (3%) were positive by RDT, 6 (6%) by microscopy and 9 (9%) by rt-PCR. Ages 5-14.9 years had the highest mean malaria parasite densities of 560 parasites/µl with Plasmodium falciparum as the dominant species in 4 participants. Moreover, in the age group ≥ 15, 2 participants (1 each) harboured P. falciparum and Plasmodium malariae parasites. RDT had a higher sensitivity (76.54%; CI95 66.82-85.54) than rt-PCR (33.33%; CI95 4.33-77.72), while both rt-PCR and RDT were observed to have a higher specificity (92.55; CI95 85.26-96.95) and (97.30; CI95 93.87-99.13), respectively in the diagnosis of malaria. CONCLUSION: In Asutsuare, Ghana, a low endemic area, the elimination of malaria may require finding individuals with asymptomatic infections. Given the low prevalence of asymptomatic individuals identified in this study and as repleted in the literature review, which favours RACD, Asutsuare is a possible setting receptive for RACD implementation.

Reactive Case Detection Strategy for Malaria Control and Elimination: A 12 Year Systematic Review and Meta-Analysis from 25 Malaria-Endemic Countries.

Reactive case detection (RACD) is the screening of household members and neighbors of index cases reported in passive surveillance. This strategy seeks asymptomatic infections and provides treatment to break transmission without testing or treating the entire population. This review discusses and highlights RACD as a recommended strategy for the detection and elimination of asymptomatic malaria as it pertains in different countries. Relevant studies published between January 2010 and September 2022 were identified mainly through PubMed and Google Scholar. Search terms included "malaria and reactive case detection", "contact tracing", "focal screening", "case investigation", "focal screen and treat". MedCalc Software was used for data analysis, and the findings from the pooled studies were analyzed using a fixed-effect model. Summary outcomes were then presented using forest plots and tables. Fifty-four (54) studies were systematically reviewed. Of these studies, 7 met the eligibility criteria based on risk of malaria infection in individuals living with an index case < 5 years old, 13 met the eligibility criteria based on risk of malaria infection in an index case household member compared with a neighbor of an index case, and 29 met the eligibility criteria based on risk of malaria infection in individuals living with index cases, and were included in the meta-analysis. Individuals living in index case households with an average risk of 2.576 (2.540-2.612) were more at risk of malaria infection and showed pooled results of high variation heterogeneity chi-square = 235.600, (p < 0.0001) I2 = 98.88 [97.87-99.89]. The pooled results showed that neighbors of index cases were 0.352 [0.301-0.412] times more likely to have a malaria infection relative to index case household members, and this result was statistically significant (p < 0.001). The identification and treatment of infectious reservoirs is critical to successful malaria elimination. Evidence to support the clustering of infections in neighborhoods, which necessitates the inclusion of neighboring households as part of the RACD strategy, was presented in this review.

Malaria Knowledge-Base and Prevalence of Parasitaemia in Asymptomatic Adults in the Forest Zone of Ghana.

PURPOSE: To determine the levels of knowledge, awareness and perception of malaria, and to determine the infection status among asymptomatic adults in selected districts. METHODS: This descriptive, cross-sectional study recruited 849 participants from seven districts in the malaria meso-endemic forest zone of Ghana. Questionnaires were administered to elicit responses from asymptomatic adults on malaria awareness, knowledge and insecticide-treated net (ITN) usage. Capillary blood samples were taken from study subjects for malaria Rapid Diagnostic Test (RDT) and microscopy. Descriptive statistics was used to analyse quantitative and qualitative data. RESULTS: Ninety-eight percent of participants were aware of malaria, 94.0% owned ITNs but only 35.5% consistently used them. Also, 56.7% correctly associated malaria with mosquitoes and 54.5% identified stagnant water as the breeding site. Twelve percent (12.2%) and 13.1% of the subjects tested positive for malaria via RDT and microscopy, respectively. Of the 111 confirmed malaria cases, 107 had Plasmodium falciparum infections, two had Plasmodium ovale infections and there were two Plasmodium falciparum-Plasmodium ovale mixed infections. CONCLUSION: Awareness and knowledge of malaria was satisfactory but this did not translate into mosquito avoidance behaviour due to deep-seated perceptions and myths. With the prevalence of asymptomatic parasitaemia observed, this reservoir of infection could be dislodged with appropriate health education targeted at women in the rural communities.

Antimicrobial resistance (AMR) and molecular characterization of Neisseria gonorrhoeae in Ghana, 2012-2015.

Neisseria gonorrhoeae antimicrobial resistance (AMR) surveillance is essential for tracking the emergence and spread of AMR strains in local, national and international populations. This is crucial for developing or refining treatment guidelines. N. gonorrhoeae multiantigen sequence typing (NG-MAST) is beneficial for describing the molecular epidemiology of gonococci at national and international levels. Elucidation of AMR determinants to ß-lactam drugs, is a means of monitoring the development of resistance. In Ghana, little is known about the current gonococcal AMR prevalence and no characterization of gonococcal isolates has been previously performed. In this study, gonococcal isolates (n = 44) collected from five health facilities in Ghana from 2012 to 2015, were examined using AMR testing, NG-MAST and sequencing of penA. High rates of resistance were identified to tetracycline (100%), benzylpenicillin (90.9%), and ciprofloxacin (81.8%). One isolate had a high cefixime MIC (0.75 µg/ml). Twenty-eight NG-MAST sequence types (STs) were identified, seventeen of which were novel. The isolate with the high cefixime MIC contained a mosaic penA-34 allele and belonged to NG-MAST ST1407, an internationally spreading multidrug-resistant clone that has accounted for most cefixime resistance in many countries. In conclusion, AMR testing, NG-MAST, and sequencing of the AMR determinant penA, revealed high rates of resistance to tetracycline, benzylpenicillin, and ciprofloxacin; as well as a highly diverse population of N. gonorrhoeae in Ghana. It is imperative to continue with enhanced AMR surveillance and to understand the molecular epidemiology of gonococcal strains circulating in Ghana and other African countries.

Reactive case detection of Plasmodium falciparum in western Kenya highlands: effective in identifying additional cases, yet limited effect on transmission.

BACKGROUND: Identifying asymptomatic reservoirs of malaria parasites using index cases as entry points into the community is potentially a cost-effective way towards achieving malaria elimination. METHODS: Within 1 year, 1430 confirmed malaria cases were identified in Marani hospital, western Kenya. Fifty cases were followed up, and 108 index case household members and 612 neighbours within a 100 m radius were screened. As controls, samples were collected from 510 individuals matched with index cases and located at a distance of ≥ 500 m from them. Infections were diagnosed by microscopy and PCR while simultaneously collecting malaria vectors indoor using pyrethrum spray catches. RESULTS: In the index case and neighbour households, the prevalence of infection was approximately twice as high as in control households (by PCR: index cases households: 28.9%, neighbours: 25.3%, matched controls: 12.9%). In index case households, the indoor vector density (Anopheles gambiae and Anopheles funestus) was higher (0.46 female/house/night) than in neighbouring (0.31 f/h/n) and control houses (0.29 f/h/n). CONCLUSIONS: Screening index case households and neighbours approximately doubles the chance to detect asymptomatic infections compared to randomly selected households. However, even if all cases were followed up, only a small proportion (˂ 10%) of the asymptomatic reservoir in the population would have been identified. Control programmes need to weigh the increased chance to find cases around index cases vs. the logistical challenges to target this subgroup within the population.

The epidemiology of lymphatic filariasis in Ghana, explained by the possible existence of two strains of Wuchereria bancrofti.

INTRODUCTION: Lymphatic filariasis is a debilitating disease caused by the filarial worm Wuchereria bancrofti. It is earmarked for elimination by the year 2020 through the Global Program for the Elimination of LF (GPELF). In Ghana, mass treatment has been on-going since the year 2000. Earlier studies have revealed differing epidemiology of LF in the North and South of Ghana. This study was therefore aimed at understanding the possible impacts of W. bancrofti diversity on the epidemiology and control of LF in Ghana. METHODS: The Mitochondrial, Cytochrome C Oxidase I gene of W. bancrofti samples was sequenced and analyzed. The test sequences were grouped into infrapopulations, and pairwise differences (π) and mutation rates (θ) were computed. The amount of variance within and among populations was also computed using the AMOVA. The evolutionary history was inferred using the Maximum Parsimony method. RESULTS: Seven samples from the South and 15 samples from the North were sequenced, and submitted to GenBank with accession numbers GQ479497- GQ479518. The results revealed higher mutation frequencies in the southern population, compared to the northern population. Haplotype analyses revealed a total of 11 haplotypes (Hap) in all the 22 DNA sequences, with high genetic variation and polymorphisms within the southern samples. CONCLUSION: This study showed that there is considerable genetic variability within W. bancrofti populations in Ghana, differences that might explain the observed epidemiology of LF. Further studies are however required for an in-depth understanding of LF epidemiology and control.

The ecology of mosquitoes in an irrigated vegetable farm in Kumasi, Ghana: abundance, productivity and survivorship.

BACKGROUND: Irrigated vegetable farms within the city of Kumasi, Ghana, create hotspots for the breeding of malaria vectors, which could lead to high transmission of malaria. This study investigated the abundance and productivity of mosquitoes in an irrigated vegetable farm in Kumasi, Ghana. METHODS: Adult mosquito productivity was estimated five days in a week in different irrigated scheme types (dug-out wells, furrows and footprints) for 12 weeks using emergence traps. Larval sampling was done five days a week to estimate the abundance of larvae from the different irrigated schemes types. RESULTS: Mosquito breeding in the irrigated vegetable field was confined to dug-out wells, furrows and human footprints. Mosquito productivity (m2/week) was highest in the dugout wells followed by the human footprints and the least was in the furrows (11.23, 5.07 and 4.34 An. gambiae/m2/week). Larval abundance for the late instars (3rd, 4th and pupae) also followed the same trend, with the dug-out wells having the highest larval abundance followed by the human footprints and then the furrows (13.24, 6.81, 5.87 larvae/week). Mosquito productivity and abundance was negatively correlated with rainfall (R2 = 0.209; P< 0.01). CONCLUSION: This study showed that adult and larval mosquito abundance and larval survival were high in the irrigated fields in the irrigated vegetable farm. This therefore, contributed significantly to adult mosquito populations and hence malaria transmission in the city.

Variation in exposure to Anopheles gambiae salivary gland peptide (gSG6-P1) across different malaria transmission settings in the western Kenya highlands.

BACKGROUND: The existing metrics of malaria transmission are limited in sensitivity under low transmission intensity. Robust surveillance systems are needed as interventions to monitor reduced transmission and prevention of rapid reintroduction. Serological tools based on antibody responses to parasite and vector antigens are potential tools for transmission measurements. The current study sought to evaluate antibody responses to Anopheles gambiae salivary gland peptide (gSG6- P1), as a biomarker of human exposure to Anopheles bites, in different transmission settings and seasons. The comparison between anti-MSP-1(19) IgG immune responders and non-responders allowed exploring the robustness of the gSG6-P1 peptide as a surveillance tool in an area of decreasing malaria transmission. METHODS: Total IgG levels to gSG6-P1 were measured in an age-stratified cohort (< 5, 5-14 and ≥ 15 years) in a total of 1,366 participants from three localities in western Kenya [Kisii (hypoendemic), Kakamega (mesoendemic), and Kombewa (hyperendemic)] including 607 sera that were additionally tested for MSP-1(19) specific responses during a low and a high malaria transmission seasons. Antibody prevalence and levels were compared between localities with different transmission intensities. Regression analysis was performed to examine the association between gSG6-P1 and MSP-1(19) seroprevalence and parasite prevalence. RESULT: Seroprevalence of gSG6-P1 in the uphill population was 36% while it was 50% valley bottom (χ(2) = 13.2, df = 1, p < 0.001). Median gSG6-P1 antibody levels in the Valley bottom were twice as high as that observed in the uphill population [4.50 vs. 2.05, p < 0.001] and showed seasonal variation. The odds of gSG6-P1 seropositives having MSP-1(19) antibodies were almost three times higher than the odds of seronegatives (OR = 2.87, 95% CI [1.977, 4.176]). The observed parasite prevalence for Kisii, Kakamega and Kombewa were 4%, 19.7% and 44.6% whilst the equivalent gSG6-P1 seroprevalence were 28%, 34% and 54%, respectively. CONCLUSION: The seroprevalence of IgG to gSG6-P1 was sensitive and robust in distinguishing between hypo, meso and hyper transmission settings and seasonal fluctuations.

The effectiveness and perception of the use of sulphadoxine-pyrimethamine in intermittent preventive treatment of malaria in pregnancy programme in Offinso district of Ashanti region, Ghana.

BACKGROUND: Malaria in pregnant women has been shown to be associated with low birth weight, stillbirth and mortality in newborns. The WHO has adopted the use of sulphadoxine-pyrimethamine (SP) to control malaria, a disease which worsens the plight of pregnant women leading to low birth weight, stillbirths and increased neonatal mortality. The present study assessed the effectiveness of SP and perception of its use in pregnant women in Offinso district (Ashanti Region), Ghana. METHOD: Pregnant women, gestational age 32 weeks prior to term, were studied from November 2006 to October 2007. Their haemoglobin levels (Hb), parasitaemia and other quantitative determinants were assessed. In-depth interviews (IDIs) and focus group discussions (FGDs) were used to assess the perception of SP usage and its effectiveness. RESULTS: Of the 306 study participants, 92 (30%) took one dose, 100 (33%) two doses and 114 (37%) three doses of SP, respectively. There was significant association between gravidity and SP dosage taken (Pearson χ2 = 18.9, p < 0.001). Although adverse effects were produced in 113 (i.e. 37%) of the pregnant women, no significant difference was observed with regard to the dosage of SP taken (Pearson's χ2 = 2.3, p ≥ 0.32). Peripheral parasitaemia was present in 47 (15%) of the subjects. There was a poor negative relationship of doses of SP with parasitaemia (r = -0.07, p ≥ 0.24). Mean Hb was 11.3 ± 1.6 g/dl, with 118 (39%) of the subjects anaemic (Hb < 11.0 g/dl), whilst 187 (61%) were normal (Hb ≥11.0 g/dl). Significant positive correlation of SP use with Hb level (r = 0.15, p < 0.008) was observed. SP use reduced malaria and anaemia prevalence, contributed to reduced maternal morbidity with mild side effects being reported. CONCLUSIONS: This study points to the effectiveness of IPTp using SP as an evidence-based measure for control of malaria and malaria-related anaemia in pregnancy. Therefore, the Ghana Health Service should improve current programme strategies to increase the proportion of pregnant women who take three doses of SP, paying attention to improved face-to-face health education, focussed antenatal care and better social mobilization.

Effect of sulphadoxine-pyrimethamine on neonatal birth weight and perceptions on its impact on malaria in pregnancy in an intermittent preventive treatment programme setting in Offinso District, Ghana.

This study evaluated the effect of sulphadoxine-pyrimethamine (SP) use in intermittent preventive treatment of malaria in pregnancy (IPTp) on birth weights of neonates in a stable malaria transmission area of Ghana, Offinso District. Routine delivery data from six health facilities over the period January 2005 to October 2007 were reviewed. In-depth interviews were conducted for health staff of these facilities to assess the effect of SP use in IPTp in pregnancy. SP-IPTp improved the birth weight of neonates and the effects of age, parity, term of pregnancy and sex of neonate also had significant influence on the birth weight (P < 0.0001). The variation in birth weight of the neonates, however, did not show significant difference (OR = 0.91, 95% CI 0.8-1.1, P ≥0.26) over the period and seasonal variations had no effect on birth weight (OR = 0.84, 95% CI 0.7-1.1, P ≥0.18). Health personnel attested to the fact that SP-IPTp had reduced the burden of malaria cases in pregnancy and improved birth weight of neonates. This study, thus, shows that successful implementation of the SP-IPTp strategy will improve the birth weight of neonates, and consequently reduce neonatal mortality.

Environmental factors associated with the distribution of Anopheles gambiae s.s in Ghana; an important vector of lymphatic filariasis and malaria.

Anopheles gambiae s.s mosquitoes are important vectors of lymphatic filariasis (LF) and malaria in Ghana. To better understand their ecological aspects and influence on disease transmission, we examined the spatial distribution of the An. gambiae (M and S) molecular forms and associated environmental factors, and determined their relationship with disease prevalence. Published and current data available on the An. gambiae species in Ghana were collected in a database for analysis, and the study sites were georeferenced and mapped. Using the An. gambiae s.s sites, environmental data were derived from climate, vegetation and remote-sensed satellite sources, and disease prevalence data from existing LF and malaria maps in the literature. The data showed that An. gambiae M and S forms were sympatric in most locations. However, the S form predominated in the central region, while the M form predominated in the northern and coastal savanna regions. Bivariate and multiple regression analyses identified temperature as a key factor distinguishing their distributions. An. gambiae M was significantly correlated with LF, and 2.5 to 3 times more prevalent in the high LF zone than low to medium zones. There were no significant associations between high prevalence An. gambiae s.s locations and malaria. The distribution of the An. gambiae M and S forms and the diseases they transmit in Ghana appear to be distinct, driven by different environmental factors. This study provides useful baseline information for disease control, and future work on the An. gambiae s.s in Ghana.

Reduction in levels of plasma vascular endothelial growth factor-A and improvement in hydrocele patients by targeting endosymbiotic Wolbachia sp. in Wuchereria bancrofti with doxycycline.

The treatment for hydrocele is expensive, invasive surgery-hydrocelectomy. A drug that could prevent or improve this condition could replace or supplement hydrocelectomy. In Ghana, 42 hydrocele patients participated in a double-blind, placebo-controlled trial of a six-week regimen of doxycycline, 200 mg/day. Four months after doxycycline treatment, patients received 150 mug/kg of ivermectin and 400 mg of albendazole, which is used for mass chemotherapy in this area. Patients were monitored for levels of Wolbachia sp., microfilaremia, antigenemia, plasma levels of vascular endothelial growth factor-A (VEGF-A) and stage/size of the hydrocele. Wolbachia sp. loads/microfilaria, microfilaremia, and antigenemia were significantly reduced in the doxycycline-treated patients compared with the placebo group. The mean plasma levels of VEGF-A were decreased significantly in the doxycycline-treated patients who had active infection. This finding preceded the reduction of the stage of hydrocele. A six-week regimen of doxycycline treatment against filariasis showed amelioration of pathologic conditions of hydrocele patients with active infection.

Deforestation and vectorial capacity of Anopheles gambiae Giles mosquitoes in malaria transmission, Kenya.

We investigated the effects of deforestation on microclimates and sporogonic development of Plasmodium falciparum parasites in Anopheles gambiae mosquitoes in an area of the western Kenyan highland prone to malaria epidemics. An. gambiae mosquitoes were fed with P. falciparum-infected blood through membrane feeders. Fed mosquitoes were placed in houses in forested and deforested areas in a highland area (1,500 m above sea level) and monitored for parasite development. Deforested sites had higher temperatures and relative humidities, and the overall infection rate of mosquitoes was increased compared with that in forested sites. Sporozoites appeared on average 1.1 days earlier in deforested areas. Vectorial capacity was estimated to be 77.7% higher in the deforested site than in the forested site. We showed that deforestation changes microclimates, leading to more rapid sporogonic development of P. falciparum and to a marked increase of malaria risk in the western Kenyan highland.

Plasma vascular endothelial growth Factor-A (VEGF-A) and VEGF-A gene polymorphism are associated with hydrocele development in lymphatic filariasis.

Hydrocele is a build-up of fluid in the scrotal regions of a proportion of men infected with the filarial nematode Wuchereria bancrofti. Vascular endothelial growth factors (VEGF) are major mediators of vascular permeability and angiogenesis in the development and progression of many diseases, making them candidates in hydrocele development. We assessed the role of VEGF-A genetic polymorphisms in hydrocele development in a cohort of lymphatic filariasis patients from Ghana. Three VEGF-A promoter polymorphisms were examined. The C/C genotype at -460 was significantly higher in hydrocele patients ([P = 0.0007], OR = 3.8 [95% CI = 1.9-8.2]) than in non-hydrocele patients. Furthermore, plasma levels of VEGF-A were significantly higher in subjects with the C/C genotype than in those with other genotypes. Also, a positive correlation (R(2) = 0.412, P = 0.026) was observed between plasma VEGF-A and stage of hydrocele. The data suggest that the C polymorphism at -460 is a genetic risk factor for hydrocele development in lymphatic filariasis.

Life-table analysis of Anopheles arabiensis in western Kenya highlands: effects of land covers on larval and adult survivorship.

In high-elevation areas in western Kenya, the abundance of Anopheles arabiensis is either very low or absent. The western Kenya highlands (an area with an elevation > 1,500m above sea level) have also been experiencing extensive deforestation, and deforestation has been suggested as one of the important factors that facilitate malaria transmission in the highlands. This study investigated whether climate conditions in the western Kenya highlands (Kakamega, elevation 1,500 m above sea level) were permissive to the development and survival of An. arabiensis and whether deforestation promoted An. arabiensis survivorship of immature and adult stages, using life-table analysis. We found that in larval habitats located in forested areas, only 4-9% of first-instar larvae developed into adults and the development length exceeded 20 days. Mean water temperature of aquatic habitats in the deforested area was 4.8-6.1 degrees C higher than that in the forested area, larval-to-adult survivorship was increased to 65-82%, and larval-to-adult development time was shortened by 8-9 days. The average indoor temperature in houses in the deforested area was 1.7-1.8 degrees C higher than in the forested area, and the relative humidity was 22-25% lower. The median survival time of adult mosquitoes in the deforested area was 49-55% higher than those in the forested area. The net reproductive rate of female mosquitoes in the deforested area was 1.7- to 2.6-fold higher than that in the forested area. Compared with previously published data on An. gambiae, the net reproductive rate of An. arabiensis was only 0.8-1.3% of Anopheles gambiae in the forested area and 2.3-2.6% in the deforested area. Therefore, the current ambient climate condition is less permissive to An. arabiensis than to An. gambiae in western Kenya highlands. However, environmental changes such as deforestation and global warming may facilitate the establishment of An. arabiensis populations in the highlands.

Doxycycline reduces plasma VEGF-C/sVEGFR-3 and improves pathology in lymphatic filariasis.

Lymphatic filariasis is a disease of considerable socioeconomic burden in the tropics. Presently used antifilarial drugs are able to strongly reduce transmission and will thus ultimately lower the burden of morbidity associated with the infection, however, a chemotherapeutic principle that directly induces a halt or improvement in the progression of the morbidity in already infected individuals would constitute a major lead. In search of such a more-effective drug to complement the existing ones, in an area endemic for bancroftian filariasis in Ghana, 33 microfilaremic and 18 lymphedema patients took part in a double-blind, placebo-controlled trial of a 6-wk regimen of 200 mg/day doxycycline. Four months after doxycycline treatment, all patients received 150-200 microg/kg ivermectin and 400 mg albendazole. Patients were monitored for Wolbachia and microfilaria loads, antigenemia, filarial dance sign (FDS), dilation of supratesticular lymphatic vessels, and plasma levels of lymphangiogenic factors (vascular endothelial growth factor-C [VEGF-C] and soluble vascular endothelial growth factor receptor-3 [(s)VEGFR-3]). Lymphedema patients were additionally monitored for stage (grade) of lymphedema and the circumferences of affected legs. Wolbachia load, microfilaremia, antigenemia, and frequency of FDS were significantly reduced in microfilaremic patients up to 24 mo in the doxycycline group compared to the placebo group. The mean dilation of supratesticular lymphatic vessels in doxycycline-treated patients was reduced significantly at 24 mo, whereas there was no improvement in the placebo group. Preceding clinical improvement, at 12 mo, the mean plasma levels of VEGF-C and sVEGFR-3 decreased significantly in the doxycycline-treated patients to a level close to that of endemic normal values, whereas there was no significant reduction in the placebo patients. The extent of disease in lymphedema patients significantly improved following doxycycline, with the mean stage of lymphedema in the doxycycline-treated patients being significantly lower compared to placebo patients 12 mo after treatment. The reduction in the stages manifested as better skin texture, a reduction of deep folds, and fewer deep skin folds. In conclusion, a 6-wk regimen of antifilarial treatment with doxycycline against W. bancrofti showed a strong macrofilaricidal activity and reduction in plasma levels of VEGF-C/sVEGFR-3, the latter being associated with amelioration of supratesticular dilated lymphatic vessels and with an improvement of pathology in lymphatic filariasis patients.

Effects of microclimatic changes caused by deforestation on the survivorship and reproductive fitness of Anopheles gambiae in western Kenya highlands.

Land use changes have been suggested as one of the causes for malaria epidemics in the African highlands. This study investigated the effects of deforestation-induced changes in indoor temperature on the survivorship and reproductive fitness of Anopheles gambiae in an epidemic prone area in the western Kenya highlands. We found that the mean indoor temperatures of houses located in the deforested area were 1.2 degrees C higher than in houses located in the forested area during the dry season and 0.7 degrees C higher during the rainy season. The mosquito mortality rate was highly age-dependent regardless of study site or season. Mosquitoes that were placed in houses in the deforested area showed a 64.8-79.5% higher fecundity than those in houses located in the forested area, but the median survival time was reduced by 5-7 days. Female mosquitoes in the deforested area showed a 38.5-40.6% increase in net reproductive rate and an 11.6-42.9% increase in intrinsic growth rate than those in the forested area. Significant increases in net reproductive rate and intrinsic growth rate for mosquitoes in the deforested area suggest that deforestation enhances mosquito reproductive fitness, increasing mosquito population growth potential in the western Kenya highlands. The vectorial capacity of An. gambiae under study was estimated at least 106% and 29% higher in the deforested area than in the forested area in dry and rainy seasons, respectively.

Effects of microclimatic changes caused by land use and land cover on duration of gonotrophic cycles of Anopheles gambiae (Diptera: Culicidae) in western Kenya highlands.

Studies were carried out at a malaria epidemic-prone highland site in western Kenya to determine the effects of deforestation-caused microclimate change on the duration of the gonotrophic cycle of the malaria vector Anopheles gambiae Giles. Gonotrophic cycle duration was measured using field-collected F1 A. gambiae females. Average ambient temperature in the deforested area of Kakamega (elevation 1,430-1,580 m above sea level), western Kenya, was 0.5 degrees C higher than that of the forested area over a 10-mo period. During the dry season, deforested areas showed an increased mean indoor temperature of 1.8 degrees C, and a shortened duration of the mosquitoes' first and second gonotrophic cycles, by 1.7 d (59%) and 0.9 d (43%). During the rainy season, the average indoor temperature of houses located in the deforested area was 1.2 degrees C higher than in houses in the forested area. The duration of the first and second gonotrophic cycles was shortened by 1.5 d (17%) and 1.4 d (27%), respectively, in the deforested highland site. A shorter mosquito gonotrophic cycle implies increased daily biting frequency and thus increased vectorial capacity. Together with evidence that deforestation reduced A. gambiae larva-to-adult developmental time and increased larval and adult survivorship, this study suggests that deforestation can further enhance malaria transmission potential in the highlands through increased indoor temperature and shortened gonotrophic cycle durations of A. gambiae mosquitoes.