Bernard Lawson

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 μg/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 Land Use and Land Cover on Duration of Gonotrophic Cycles of Anopheles gambiae (Diptera: Culicidae) in Western Kenya Highlands

Abstract 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°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°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°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.

Deforestation and Vectorial Capacity of Anopheles gambiae Giles Mosquitoes in Malaria Transmission, Kenya

One-sentence summary for table of contents: Land use changes are affecting malaria transmission in this region.

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.

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

BackgroundThe 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-119 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.MethodsTotal 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-119 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-119 seroprevalence and parasite prevalence.ResultSeroprevalence of gSG6-P1 in the uphill population was 36% while it was 50% valley bottom (χ2 = 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-119 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.ConclusionThe 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

BackgroundMalaria 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.MethodPregnant 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.ResultsOf 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 (Pearsons 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.ConclusionsThis 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.

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

BackgroundIrrigated 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.MethodsAdult 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.ResultsMosquito 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).ConclusionThis 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.

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.