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Mansonella perstans filariasis in Uganda: patterns of microfilaraemia and clinical manifestations in two endemic communities

Identifieur interne : 000539 ( Istex/Corpus ); précédent : 000538; suivant : 000540

Mansonella perstans filariasis in Uganda: patterns of microfilaraemia and clinical manifestations in two endemic communities

Auteurs : Santa Maria Asio ; Paul E. Simonsen ; Ambrose W. Onapa

Source :

RBID : ISTEX:0B9C926101D420799A225B1CD1334D4746B136CD

English descriptors

Abstract

Surveys for Mansonella perstans infection and potentially related clinical manifestations were undertaken in two endemic communities in Mukono and Luwero districts of Uganda where no other human filarial infections are transmitted. A sensitive and accurate counting chamber method was used for quantifying microfilaraemia in 100 μl of finger-prick blood. Among 575 and 991 examined individuals aged ≥1 year in the two communities, the overall microfilariae (mf) prevalence was significantly higher in Mukono (76.5%) than in Luwero (57.7%). As early as age 1–4 years, 40.6% and 20.5% of the children were mf-positive. Prevalences increased rapidly with increasing age to reach 89.2% and 81.4% in the 15–19 years age group and then remained high in subsequent age groups. The geometric mean mf intensity among mf-positive individuals was slightly higher in the Mukono community (32.4 mf/100 μl) than in the Luwero community (29.9 mf/100 μl), and this parameter increased with age in both communities. No obvious associations were observed between various clinical parameters and M. perstans microfilaraemia in any of the study communities. The observed patterns of microfilaraemia and the lack of obvious visible clinical manifestations suggest that the host's regulatory responses are downregulated in M. perstans infections. [ClinicalTrials.gov identifier: NCT00215280]

Url:
DOI: 10.1016/j.trstmh.2008.08.007

Links to Exploration step

ISTEX:0B9C926101D420799A225B1CD1334D4746B136CD

Le document en format XML

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<div type="abstract">Surveys for Mansonella perstans infection and potentially related clinical manifestations were undertaken in two endemic communities in Mukono and Luwero districts of Uganda where no other human filarial infections are transmitted. A sensitive and accurate counting chamber method was used for quantifying microfilaraemia in 100 μl of finger-prick blood. Among 575 and 991 examined individuals aged ≥1 year in the two communities, the overall microfilariae (mf) prevalence was significantly higher in Mukono (76.5%) than in Luwero (57.7%). As early as age 1–4 years, 40.6% and 20.5% of the children were mf-positive. Prevalences increased rapidly with increasing age to reach 89.2% and 81.4% in the 15–19 years age group and then remained high in subsequent age groups. The geometric mean mf intensity among mf-positive individuals was slightly higher in the Mukono community (32.4 mf/100 μl) than in the Luwero community (29.9 mf/100 μl), and this parameter increased with age in both communities. No obvious associations were observed between various clinical parameters and M. perstans microfilaraemia in any of the study communities. The observed patterns of microfilaraemia and the lack of obvious visible clinical manifestations suggest that the host's regulatory responses are downregulated in M. perstans infections. [ClinicalTrials.gov identifier: NCT00215280]</div>
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<italic>Mansonella perstans</italic>
filariasis in Uganda: patterns of microfilaraemia and clinical manifestations in two endemic communities</article-title>
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<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Asio</surname>
<given-names>Santa Maria</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
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<name>
<surname>Simonsen</surname>
<given-names>Paul E.</given-names>
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<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Onapa</surname>
<given-names>Ambrose W.</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>c</sup>
</xref>
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<aff id="aff1">
<label>a</label>
Kyambogo University, P.O. Box 1, Kyambogo, Kampala, Uganda</aff>
<aff id="aff2">
<label>b</label>
DBL — Centre for Health Research and Development, Faculty of Life Sciences, University of Copenhagen, Thorvaldsensvej 57, 1871 Frederiksberg C, Denmark</aff>
<aff id="aff3">
<label>c</label>
Vector Control Division, Ministry of Health, P.O. Box 1661, Kampala, Uganda</aff>
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Corresponding author. Tel.: +45 3533 1415; fax: +45 3533 1433.
<italic>E-mail address:</italic>
<email>pesi@life.ku.dk</email>
(P.E. Simonsen).</corresp>
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<day>17</day>
<month>6</month>
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<day>8</day>
<month>8</month>
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<abstract>
<title>Summary</title>
<p>Surveys for
<italic>Mansonella perstans</italic>
infection and potentially related clinical manifestations were undertaken in two endemic communities in Mukono and Luwero districts of Uganda where no other human filarial infections are transmitted. A sensitive and accurate counting chamber method was used for quantifying microfilaraemia in 100 μl of finger-prick blood. Among 575 and 991 examined individuals aged ≥1 year in the two communities, the overall microfilariae (mf) prevalence was significantly higher in Mukono (76.5%) than in Luwero (57.7%). As early as age 1–4 years, 40.6% and 20.5% of the children were mf-positive. Prevalences increased rapidly with increasing age to reach 89.2% and 81.4% in the 15–19 years age group and then remained high in subsequent age groups. The geometric mean mf intensity among mf-positive individuals was slightly higher in the Mukono community (32.4 mf/100 μl) than in the Luwero community (29.9 mf/100 μl), and this parameter increased with age in both communities. No obvious associations were observed between various clinical parameters and
<italic>M. perstans</italic>
microfilaraemia in any of the study communities. The observed patterns of microfilaraemia and the lack of obvious visible clinical manifestations suggest that the host's regulatory responses are downregulated in
<italic>M. perstans</italic>
infections. [ClinicalTrials.gov identifier:
<ext-link ext-link-type="uri" xlink:href="NCT00215280">NCT00215280</ext-link>
]</p>
</abstract>
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<title>Keywords</title>
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<italic>Mansonella perstans</italic>
</kwd>
<kwd>Filariasis</kwd>
<kwd>Epidemiology</kwd>
<kwd>Microfilaraemia</kwd>
<kwd>Morbidity</kwd>
<kwd>Uganda</kwd>
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<body>
<sec sec-type="intro">
<label>1</label>
<title>Introduction</title>
<p>
<italic>Mansonella perstans</italic>
is a human filarial parasite that is widely distributed in Africa and also occurs in parts of Central and South America and the Caribbean.
<sup>
<xref ref-type="bibr" rid="bib1">1</xref>
<xref ref-type="bibr" rid="bib3">3</xref>
</sup>
It is transmitted by tiny biting midges of the genus
<italic>Culicoides</italic>
. Adult worms have only rarely been recovered but appear to live mainly in the peritoneal cavity, whereas the microfilariae (mf) circulate in the blood.</p>
<p>Despite the widespread occurrence of
<italic>M. perstans</italic>
infection, only a few studies have been carried out on the epidemiology and morbidity of this infection in endemic populations. Interest in
<italic>M. perstans</italic>
infection has been limited partly because the infection is mainly found among poor people living in rural areas and partly because it has been difficult to associate with a clear and specific clinical picture. Moreover, much of the little knowledge available has emerged as a byproduct of studies on other human filarial parasites (especially
<italic>Wuchereria bancrofti</italic>
,
<italic>Loa loa</italic>
and
<italic>Onchocerca volvulus</italic>
) in which some of the study individuals have had co-infection with
<italic>M. perstans</italic>
as well as from case reports mainly based on examination of expatriates returning from endemic areas to their home countries.</p>
<p>The general pattern of
<italic>M. perstans</italic>
microfilaraemia reported from endemic human populations appears to be a lower prevalence in children than in adults and usually also a lower prevalence in females than in males.
<sup>
<xref ref-type="bibr" rid="bib4">4</xref>
<xref ref-type="bibr" rid="bib14">14</xref>
</sup>
However, most surveys have used rather insensitive blood films for diagnosis, and microfilarial intensities have rarely been reported or analysed in detail. Some reports have associated the presence of
<italic>M. perstans</italic>
microfilaraemia with disease manifestations such as generalised itching of skin, joint and/or muscle ache, severe pain in the abdomen and liver region, neurological and psychic symptoms, endocrinological disturbances, recurrent lymphoedema in the limbs and face resembling Calabar swellings, and nodules containing adult worms in the conjunctiva or eyelids,
<sup>
<xref ref-type="bibr" rid="bib15">15</xref>
<xref ref-type="bibr" rid="bib19">19</xref>
</sup>
but the frequency of these manifestations in
<italic>M. perstans</italic>
-endemic communities has not been assessed.</p>
<p>Infection with
<italic>M. perstans</italic>
is very common in Uganda, as demonstrated in a recent countrywide survey.
<sup>
<xref ref-type="bibr" rid="bib20">20</xref>
</sup>
Two of the identified endemic areas, located in Mukono and Luwero districts, that had medium to high prevalence of
<italic>M. perstans</italic>
microfilaraemia and where no other human filarial infections are known to be transmitted were selected for further studies on the epidemiology and treatment of
<italic>M. perstans</italic>
infection. The present study analysed the patterns of
<italic>M. perstans</italic>
microfilaraemia and clinical manifestations potentially related to this infection in the two communities.</p>
</sec>
<sec sec-type="materials|methods">
<label>2</label>
<title>Materials and methods</title>
<sec>
<label>2.1</label>
<title>Study areas and study populations</title>
<p>The study was carried out in Uganda in two neighbouring villages in Mukono district (Makenke and Nsaabwa I) in November 2005 and in three neighbouring villages in Luwero district (Balita-Kibanda-Katuugo, Mijumwa and Wakyato) in January 2006. The areas were known to be highly endemic for
<italic>M. perstans</italic>
infection from earlier screening of schoolchildren.
<sup>
<xref ref-type="bibr" rid="bib20">20</xref>
</sup>
The study communities in both districts are located in fairly flat bushland at an altitude of approximately 1100 m and they border extensive swamps. The Makenke and Nsaabwa I villages are situated approximately 50 km to the north of Mukono town, which is on the Kampala–Jinja highway. They both boarder the River Sezibwa and its associated swamps on their east side. Domestic water is collected mainly from communal bore holes with hand pumps but some people also collect water from the swamp and from an unprotected spring between the two villages. The villages of Balita-Kibanda-Katuugo, Mijumwa and Wakyato are situated approximately 35 km to the west of Luwero town, which is on the Kampala–Gulu highway. They boarder the River Mayanja and its swamps on their west side. The river and some bore holes with hand pumps supply the villages with domestic water.</p>
<p>The majority of inhabitants in both areas are Baganda. The populations mainly practice subsistence farming (bananas, cassava, sweet potatoes, maize, beans and other types of vegetables) and keep animals (cows, goats, sheep, pigs, ducks, chickens and pigeons) on a small scale. Some coffee is also grown as a cash crop, and a few males are engaged in charcoal burning. In the Luwero study area there are also a few large farms that keep cattle, and milk is produced in large quantities both for local consumption and for commercial supply to the major towns. Most houses in both areas have brick walls and are roofed with iron sheets. Few houses have mud walls and are roofed with dried grass or iron sheets.</p>
</sec>
<sec>
<label>2.2</label>
<title>Census and mapping of the study communities</title>
<p>Before any activities started, meetings were held with the relevant District Directors of Health Services to seek their permission and co-operation. Meetings were also held with the local health authorities, the local councillors and the study populations to sensitise them and to explain the purpose and implications of the study. Individuals from each study community were registered in a house-to-house census, during which houses were numbered and inhabitants living in each numbered house had their name, age and sex recorded. Written informed consent to participate in the study was obtained from individuals aged ≥12 years and from the parents of younger individuals. Inclusion into the study was completely voluntary and study individuals were free to withdraw at any time without negative consequences.</p>
</sec>
<sec>
<label>2.3</label>
<title>Blood examinations for filarial infection</title>
<p>The microfilarial intensity was quantified using a counting chamber technique. Finger-prick blood samples (100 μl) were collected during the day time using calibrated heparinised capillary tubes. The blood was immediately transferred to specimen tubes with 1 ml of fixative. Later in the laboratory the specimens were examined in a Sedgewick–Rafter counting chamber under a microscope with a magnification of 100×. The specimens were left for 1 h for the tiny mf to sediment before examination and counting started.</p>
<p>In preliminary investigations, 3% acetic acid was used as the fixative since this is normally used for counting chamber technique diagnosis of
<italic>W. bancrofti</italic>
microfilaraemia.
<sup>
<xref ref-type="bibr" rid="bib21">21</xref>
</sup>
However, it was very difficult to see the tiny
<italic>M. perstans</italic>
mf in these specimens. Another fixative, Macgregor's solution, which is normally used for fixing larvae of insects, was therefore tried out and in this solution the
<italic>M. perstans</italic>
mf were more easily recognised. Macgregor's solution was prepared according to Smart.
<sup>
<xref ref-type="bibr" rid="bib22">22</xref>
</sup>
Briefly, 5 g of borax powder (sodium tetraborate) was dissolved in distilled water, 2.5 ml of glycerine and 100 ml of 40% formaldehyde was added, and finally distilled water was added to make up to 1000 ml. To reduce the irritating smell from the formalin, the Macgregor's solution was diluted to 50% by addition of distilled water before use. This was found not to reduce its suitability for detecting mf. For the same reason, microscopic examination of the specimens took place in a well ventilated laboratory.</p>
<p>Thick blood films (made from three drops of blood) were prepared from approximately 10% of the villagers at pre treatment. The blood films were dried, dehaemoglobinised, fixed with methanol, stained with Giemsa stain and the species of mf present were identified under a microscope. All mf observed were
<italic>M. perstans</italic>
. Moreover, Rapid NOW Filariasis ICT card tests (Binax Inc., Portland, ME, USA) were used at the start of the study to check all villagers for
<italic>W. bancrofti</italic>
-specific circulating filarial antigens (CFA). All these tests were negative.</p>
</sec>
<sec>
<label>2.4</label>
<title>Clinical surveys</title>
<p>Clinical investigations were carried out by a clinical officer in the day time, before blood sampling. They comprised individual clinical examinations followed by questions to the individual about clinical history. Manifestations previously reported in relation to
<italic>M. perstans</italic>
infection were particularly looked for
<sup>
<xref ref-type="bibr" rid="bib15">15</xref>
<xref ref-type="bibr" rid="bib17">17</xref>
</sup>
and these were reported in a checklist form.</p>
</sec>
<sec>
<label>2.5</label>
<title>Data analysis</title>
<p>Microfilarial geometric mean intensities (GMI) were calculated as antilog [(Σlog
<sub>10</sub>
<italic>x</italic>
 + 1)/
<italic>n</italic>
] − 1, with
<italic>x</italic>
being the individual mf intensities per 100 μl of blood and
<italic>n</italic>
the number of individuals included in the calculations. GMIs were compared statistically by independent sample
<italic>t</italic>
-tests on the log-transformed values, and prevalences were compared by χ
<sup>2</sup>
tests.
<italic>P</italic>
-values of <0.05 were considered statistically significant.</p>
</sec>
</sec>
<sec sec-type="results">
<label>3</label>
<title>Results</title>
<sec>
<label>3.1</label>
<title>Characterisation of study populations</title>
<p>The study populations in Mukono and Luwero districts had 716 and 1192 inhabitants aged ≥1 year, respectively (
<xref ref-type="fig" rid="tbl1">Table 1</xref>
<fig id="tbl1">
<label>Table 1</label>
<caption>
<p>Characteristics of the study populations in Mukono and Luwero districts</p>
</caption>
<graphic mimetype="image" xlink:href="103-3-266-tbl001.tif"></graphic>
</fig>
). Among these, 575 (80.3%) and 991 (83.1%), respectively, were examined for
<italic>M. perstans</italic>
mf. An almost equal number of males and females were examined for mf in the two communities, and neither the sex ratio nor the mean age of those examined differed significantly between the communities (χ
<sup>2</sup>
test,
<italic>P</italic>
 = 0.74 and
<italic>t</italic>
-test,
<italic>P</italic>
 = 0.58, respectively). The great majority of those examined for mf also participated in the clinical surveys (
<xref ref-type="fig" rid="tbl1">Table 1</xref>
).</p>
</sec>
<sec>
<label>3.2</label>
<title>Microfilaraemia</title>
<p>The overall mf prevalence was significantly higher in the Mukono population than in the Luwero population (76.5% vs. 57.7%; χ
<sup>2</sup>
test,
<italic>P</italic>
 < 0.001) (
<xref ref-type="fig" rid="tbl1">Table 1</xref>
), and for all age groups the mf prevalence was higher in the former than the later population (
<xref ref-type="fig" rid="tbl2">Table 2</xref>
<fig id="tbl2">
<label>Table 2</label>
<caption>
<p>Population size and
<italic>Mansonella perstans</italic>
microfilaraemia in relation to age group and sex in the study populations from Mukono and Luwero districts</p>
</caption>
<graphic mimetype="image" xlink:href="103-3-266-tbl002.tif"></graphic>
</fig>
;
<xref ref-type="fig" rid="fig1">Figure 1</xref>
A
<fig id="fig1" position="float">
<label>Figure 1</label>
<caption>
<p>
<italic>Mansonella perstans</italic>
microfilaraemia in relation to age group in the study populations from Mukono and Luwero districts: (A) microfilariae (mf) prevalence; (B) mf geometric mean intensity (GMI) among all examined individuals; and (C) mf GMI among mf-positive individuals.</p>
</caption>
<graphic mimetype="image" xlink:href="103-3-266-fig001.jpg"></graphic>
</fig>
). As early as age 1–4 years, 40.6% and 20.5% of the children were positive for mf in the Mukono and Luwero populations, respectively. Prevalences then increased rapidly with increasing age and reached 89.2% and 81.4% in the 15–19 years age group. In subsequent age groups, prevalences remained high in both communities, with a tendency for a slight further increase in Mukono and for a slight decrease in Luwero. Overall mf prevalences in males and females were almost similar in both communities (75.6% vs. 77.5% in Mukono and 59.0% vs. 56.3% in Luwero;
<xref ref-type="fig" rid="tbl2">Table 2</xref>
; χ
<sup>2</sup>
test,
<italic>P</italic>
 = 0.60 and
<italic>P</italic>
 = 0.39, respectively). In adults (≥20 years), prevalences were higher in males than in females but the differences did not reach statistical significance (93.5% vs. 84.3% in Mukono and 69.3% vs. 61.9% in Luwero; χ
<sup>2</sup>
test,
<italic>P</italic>
 = 0.06 and
<italic>P</italic>
 = 0.14, respectively).</p>
<p>The mf GMI for all examined individuals was also significantly higher in the Mukono than the Luwero population (13.7 vs. 6.2 mf/100 μl blood;
<italic>t</italic>
-test,
<italic>P</italic>
 < 0.001) (
<xref ref-type="fig" rid="tbl1">Table 1</xref>
), and in all age groups this parameter was higher in the former than in the latter population (
<xref ref-type="fig" rid="tbl2">Table 2</xref>
;
<xref ref-type="fig" rid="fig1">Figure 1</xref>
B). A gradual increase in mf GMI for all examined individuals was seen with increasing age group in both populations, which was more pronounced in Mukono than Luwero. The overall mf GMI for all examined individuals was slightly but not significantly higher in males than females in both communities (14.3 vs. 13.1 mf/100 μl blood in Mukono and 7.0 vs. 5.5 mf/100 μl blood in Luwero;
<xref ref-type="fig" rid="tbl2">Table 2</xref>
;
<italic>t</italic>
-test,
<italic>P</italic>
 = 0.63 and
<italic>P</italic>
 = 0.15, respectively). However, when analysing the data for adults ≥20 years, the mf GMI for all examined individuals was significantly higher in males than in females in both communities (55.8 vs. 26.7 mf/100 μl blood in Mukono and 20.5 vs. 9.1 mf/100 μl blood in Luwero;
<italic>t</italic>
-test,
<italic>P</italic>
 = 0.024 and
<italic>P</italic>
 = 0.004, respectively).</p>
<p>The mf GMI among mf-positive individuals only was slightly but not significantly higher in the Mukono than in the Luwero population (32.4 vs. 29.9 mf/100 μl blood;
<italic>t</italic>
-test,
<italic>P</italic>
 = 0.47) (
<xref ref-type="fig" rid="tbl1">Table 1</xref>
), and this parameter increased rather similarly with age in both communities (
<xref ref-type="fig" rid="tbl2">Table 2</xref>
;
<xref ref-type="fig" rid="fig1">Figure 1</xref>
C). The overall mf GMI for mf-positives was slightly but not significantly higher in males than in females in both communities (35.8 vs. 29.3 mf/100 μl blood in Mukono and 32.8 vs. 26.9 mf/100 μl blood in Luwero;
<xref ref-type="fig" rid="tbl2">Table 2</xref>
;
<italic>t</italic>
-test,
<italic>P</italic>
 = 0.22 for both tests). When analysing the data from adults ≥20 years, the mf GMI for mf-positives was considerably higher for males than for females in both communities, and the difference was significant in Luwero but not in Mukono (74.2 vs. 50.5 mf/100 μl blood in Mukono and 82.6 vs. 41.0 mf/100 μl blood in Luwero;
<italic>t</italic>
-test,
<italic>P</italic>
 = 0.18 and
<italic>P</italic>
 = 0.007, respectively).</p>
</sec>
<sec>
<label>3.3</label>
<title>Clinical manifestations</title>
<p>The findings from the clinical surveys in the Mukono and Luwero study populations are listed in relation to the mf status of the individuals in
<xref ref-type="fig" rid="tbl3">Table 3</xref>
<fig id="tbl3">
<label>Table 3</label>
<caption>
<p>Survey for clinical indicators (current manifestations and clinical history) in relation to
<italic>Mansonella perstans</italic>
microfilariae (mf) status in the study populations from Mukono and Luwero districts
<sup>a</sup>
</p>
</caption>
<graphic mimetype="image" xlink:href="103-3-266-tbl003.tif"></graphic>
</fig>
. The prevalence of some of the more common clinical manifestations (e.g. headache, stomach ache) differed considerably between the two study populations, but there was no obvious association between clinical indicators (neither clinical manifestations nor clinical history) and mf status. Statistical analysis of clinical indicators from individuals ≥1 year indicated significantly higher prevalences of headache in Luwero but not in Mukono among mf-positives than among mf-negatives (χ
<sup>2</sup>
test,
<italic>P</italic>
 = 0.002 and
<italic>P</italic>
 = 0.26, respectively). Similarly, prevalences of history of swollen eye lids (bung-eye) were significantly higher in mf-positives than among mf-negatives in Luwero but not in Mukono (χ
<sup>2</sup>
test,
<italic>P</italic>
 = 0.027 and
<italic>P</italic>
 = 0.58, respectively). Statistical analysis of clinical indicators from individuals ≥20 years indicated that none of these occurred with significantly higher prevalence in mf-positive than mf-negative individuals in any of the communities (χ
<sup>2</sup>
test,
<italic>P</italic>
 > 0.05 for all tests), but bung-eye still occurred with a higher prevalence in mf-positive than mf-negative individuals in Luwero.</p>
</sec>
</sec>
<sec sec-type="discussion">
<label>4</label>
<title>Discussion</title>
<p>The two study communities, which both had high levels of
<italic>M. perstans</italic>
endemicity, were located approximately 70 km apart in Mukono and Luwero districts. Previous surveys have indicated that the two study areas are free from infection with the human filarial parasites
<italic>W. bancrofti</italic>
and
<italic>O. volvulus</italic>
<sup>
<xref ref-type="bibr" rid="bib23">23</xref>
,
<xref ref-type="bibr" rid="bib24">24</xref>
</sup>
and there was no evidence from the present study that
<italic>W. bancrofti</italic>
is transmitted in the areas, either from the mf examinations or from the examinations for
<italic>W. bancrofti</italic>
-specific CFA.</p>
<p>
<italic>Mansonella perstans</italic>
infection was common even in the youngest age group, with 40.6% and 20.5% of 1–4-year-old children being mf-positive in the Mukono and Luwero study communities, respectively. High
<italic>M. perstans</italic>
mf prevalences in small children have also been reported from other endemic areas.
<sup>
<xref ref-type="bibr" rid="bib4">4</xref>
,
<xref ref-type="bibr" rid="bib6">6</xref>
,
<xref ref-type="bibr" rid="bib8">8</xref>
</sup>
This is in contrast to what is seen in
<italic>W. bancrofti</italic>
-endemic areas, where microfilaraemia with this related filarial species is rarely seen in children <5 years of age.
<sup>
<xref ref-type="bibr" rid="bib3">3</xref>
</sup>
Jordan suggested that it may be easier for
<italic>M. perstans</italic>
adult males and females to find each other and mate in the peritoneal cavity of the infected individual than for
<italic>W. bancrofti</italic>
adult worms in the widespread lymphatic system.
<sup>
<xref ref-type="bibr" rid="bib6">6</xref>
</sup>
Another, perhaps more likely, explanation could be that the hosts only mount a weak and limited regulatory response to
<italic>M. perstans</italic>
infection, thus allowing the parasites to establish more easily.</p>
<p>The overall community mf prevalence and mf GMI was significantly higher in the Mukono than the Luwero study community. In both communities, mf prevalences increased rapidly with increasing age up to 15–19 years, and from then on remained high in adult life. Higher mf prevalences in adults than in children have similarly been reported from other endemic areas.
<sup>
<xref ref-type="bibr" rid="bib4">4</xref>
,
<xref ref-type="bibr" rid="bib6">6</xref>
,
<xref ref-type="bibr" rid="bib8">8</xref>
–12,
<xref ref-type="bibr" rid="bib14">14</xref>
</sup>
The mf mean intensities continued to increase with increasing age in both study communities (both when assessed for all individuals and for mf-positive individuals only). The observed age–prevalence and age–intensity patterns for
<italic>M. perstans</italic>
microfilaraemia again suggest that functional host regulatory responses, which would otherwise have been expected to reduce the prevalence and mean intensity in the higher age groups, are limited or downregulated in this infection.
<sup>
<xref ref-type="bibr" rid="bib25">25</xref>
</sup>
If effective immune regulatory mechanisms had been at play, it would furthermore have been expected that both mf prevalence and mean intensity would peak earlier and decrease faster in the community with the higher (Mukono) than in the community with the lower (Luwero) transmission intensity. In fact, the opposite trend was seen for mf prevalence, with a slight increase in Mukono and a slight decrease in Luwero with increasing age.</p>
<p>In both communities, mf prevalences and mean intensities were higher in adult males than in adult females, and for mf intensities this difference reached statistical significance. This finding is consistent with several other studies which have reported that adult males are more frequently infected than adult females.
<sup>
<xref ref-type="bibr" rid="bib7">7</xref>
<xref ref-type="bibr" rid="bib10">10</xref>
,
<xref ref-type="bibr" rid="bib12">12</xref>
,
<xref ref-type="bibr" rid="bib14">14</xref>
,
<xref ref-type="bibr" rid="bib26">26</xref>
</sup>
The difference in infection frequency and intensity between males and females could probably be explained by differences in exposure to the vector, but it is also possible that physiological differences between the sexes, resulting in different susceptibility, may be a contributing factor. A similar picture of higher mf prevalences and intensities in males than in females is also commonly reported for
<italic>W. bancrofti</italic>
and
<italic>O. volvulus</italic>
in areas endemic for these parasites.
<sup>
<xref ref-type="bibr" rid="bib27">27</xref>
,
<xref ref-type="bibr" rid="bib28">28</xref>
</sup>
</p>
<p>During the clinical surveys, signs and symptoms earlier reported to be, or potentially be, due to
<italic>M. perstans</italic>
were particularly looked for.
<sup>
<xref ref-type="bibr" rid="bib15">15</xref>
<xref ref-type="bibr" rid="bib17">17</xref>
</sup>
These earlier studies were based on examination of patients (including expatriates who had visited endemic areas) reporting with their manifestations to medical clinics, and knowledge about the occurrence and frequency of manifestations due to
<italic>M. perstans</italic>
infection in endemic communities is largely unknown. The frequency of the manifestations differed between the study communities (likely because of different living conditions), but no obvious associations were observed between the selected clinical indicators and mf status. There may be several reasons for the failure to identify obvious visible negative clinical consequences of
<italic>M. perstans</italic>
infection. First, it is possible that some of the earlier reported manifestations are rare and therefore were not detected with high enough frequency to show a significant association with microfilaraemia in the present study. Second, the high level of endemicity reduced the ability to detect a significant difference in frequency of manifestations between the mf-positive and -negative groups (especially in adults). Third, the previously reported manifestations may be more common in expatriates exposed to infection later in life than in individuals who have grown up in the endemic environment. Fourth, manifestations may be more related to adult worm infection or to exposure to infective larvae than to microfilaraemia.</p>
<p>It is also possible that there could be other common but yet unrecognised (and perhaps not easily noticed) manifestations or clinical consequences that the study individuals were not examined for. As mentioned above, the observed infection patterns suggest that host regulatory mechanisms are limited in
<italic>M. perstans</italic>
infections, and the lack of obvious clinical manifestations could in fact be a result of this. It may be speculated that strong immune responses are downregulated to prevent development of inflammatory responses to the parasite that would induce pathology in the host at the same time. The occurrence and mechanisms of this downregulation and whether it is specifically related to the
<italic>M. perstans</italic>
infection or has a more general nature should be a key issue for future research on this parasite. Interestingly, it was recently reported from a study in Uganda that individuals with
<italic>M. perstans</italic>
infection were significantly less likely to respond positively in a skin prick test for common allergens than uninfected individuals,
<sup>
<xref ref-type="bibr" rid="bib29">29</xref>
</sup>
thus again suggesting that the
<italic>M. perstans</italic>
infection has immunomodulatory properties. As
<italic>M. perstans</italic>
infection prevails in areas where many other types of infections are common (including malaria, tuberculosis and HIV), more knowledge on its interference with the host's immune response as well as with other infections is urgently needed.</p>
</sec>
<sec>
<title>Funding</title>
<p>The study received financial support from DBL – Centre for Health Research and Development, Denmark.</p>
</sec>
<sec>
<title>Conflicts of interest</title>
<p>None declared.</p>
</sec>
<sec>
<title>Ethical approval</title>
<p>The National Council for Science and Technology in Uganda provided research and ethical clearance, and the study protocol was reviewed by the Danish National Committee for Biomedical Research Ethics. The study was registered at
<ext-link ext-link-type="uri" xlink:href="www.ClinicalTrials.gov">www.ClinicalTrials.gov</ext-link>
with identifier
<ext-link ext-link-type="uri" xlink:href="NCT00215280">NCT00215280</ext-link>
.</p>
</sec>
<sec>
<title>Authors' contributions</title>
<p>All authors conceived and designed the study; SMA carried out the field and laboratory work under the supervision of AWO and PES; SMA and PES analysed and interpreted the data and drafted the manuscript. All authors read and approved the final manuscript. SMA and PES are guarantors of the paper.</p>
</sec>
</body>
<back>
<ack>
<title>Acknowledgements</title>
<p>The authors are grateful to the study communities in Mukono and Luwero districts for their co-operation, to the local counsellors for their untiring efforts in mobilisation, to the clinical officers from Seeta Namanoga Health Centre (Stephen Lubanga) and Wakyato Health Centre (Mpaulo Don Williams) for their commitment in community census and clinical examinations, and to the LF technical staff of the Vector Control Division, Kampala (Anna Auma, Betty Nabatte, Harriet Namanya, Abudalha Bagonza, Peter Ekaju and Hamisi Kakoma) and the Department of Zoology, Makerere University, Kampala (Virginia Katende and Madinah Namyalo) for the tedious but excellent work of specimen collection in the field and analyses in the laboratory.</p>
</ack>
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<namePart type="given">Santa Maria</namePart>
<namePart type="family">Asio</namePart>
<affiliation>Kyambogo University, P.O. Box 1, Kyambogo, Kampala, Uganda</affiliation>
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<namePart type="given">Paul E.</namePart>
<namePart type="family">Simonsen</namePart>
<affiliation>DBL — Centre for Health Research and Development, Faculty of Life Sciences, University of Copenhagen, Thorvaldsensvej 57, 1871 Frederiksberg C, Denmark</affiliation>
<affiliation>E-mail: pesi@life.ku.dk</affiliation>
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<namePart type="given">Ambrose W.</namePart>
<namePart type="family">Onapa</namePart>
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<abstract>Surveys for Mansonella perstans infection and potentially related clinical manifestations were undertaken in two endemic communities in Mukono and Luwero districts of Uganda where no other human filarial infections are transmitted. A sensitive and accurate counting chamber method was used for quantifying microfilaraemia in 100 μl of finger-prick blood. Among 575 and 991 examined individuals aged ≥1 year in the two communities, the overall microfilariae (mf) prevalence was significantly higher in Mukono (76.5%) than in Luwero (57.7%). As early as age 1–4 years, 40.6% and 20.5% of the children were mf-positive. Prevalences increased rapidly with increasing age to reach 89.2% and 81.4% in the 15–19 years age group and then remained high in subsequent age groups. The geometric mean mf intensity among mf-positive individuals was slightly higher in the Mukono community (32.4 mf/100 μl) than in the Luwero community (29.9 mf/100 μl), and this parameter increased with age in both communities. No obvious associations were observed between various clinical parameters and M. perstans microfilaraemia in any of the study communities. The observed patterns of microfilaraemia and the lack of obvious visible clinical manifestations suggest that the host's regulatory responses are downregulated in M. perstans infections. [ClinicalTrials.gov identifier: NCT00215280]</abstract>
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<genre>Keywords</genre>
<topic>Filariasis</topic>
<topic>Epidemiology</topic>
<topic>Microfilaraemia</topic>
<topic>Morbidity</topic>
<topic>Uganda</topic>
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<identifier type="ISSN">0035-9203</identifier>
<identifier type="eISSN">1878-3503</identifier>
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<number>103</number>
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<start>266</start>
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<identifier type="DOI">10.1016/j.trstmh.2008.08.007</identifier>
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