Hydric stress-dependent effects of Plasmodium falciparum infection on the survival of wild-caught Anopheles gambiae female mosquitoes

<p>Abstract</p> <p>Background</p> <p>Whether <it>Plasmodium falciparum</it>, the agent of human malaria responsible for over a million deaths per year, causes fitness costs in its mosquito vectors is a burning question that has not yet been adequately resolved. Understanding the evolutionary forces responsible for the maintenance of susceptibility and refractory alleles in natural mosquito populations is critical for understanding malaria transmission dynamics.</p> <p>Methods</p> <p>In natural mosquito populations, <it>Plasmodium </it>fitness costs may only be expressed in combination with other environmental stress factors hence this hypothesis was tested experimentally. Wild-caught blood-fed <it>Anopheles gambiae </it>s.s. females of the M and S molecular form from an area endemic for malaria in Mali, West Africa, were brought to the laboratory and submitted to a 7-day period of mild hydric stress or kept with water ad-libitum. At the end of this experiment all females were submitted to intense desiccation until death. The survival of all females throughout both stress episodes, as well as their body size and infection status was recorded. The importance of stress, body size and molecular form on infection prevalence and female survival was investigated using Logistic Regression and Proportional-Hazard analysis.</p> <p>Results</p> <p>Females subjected to mild stress exhibited patterns of survival and prevalence of infection compatible with increased parasite-induced mortality compared to non-stressed females. Fitness costs seemed to be linked to ookinetes and early oocyst development but not the presence of sporozoites. In addition, when females were subjected to intense desiccation stress, those carrying oocysts exhibited drastically reduced survival but those carrying sporozoites were unaffected. No significant differences in prevalence of infection and infection-induced mortality were found between the M and S molecular forms of <it>Anopheles gambiae</it>.</p> <p>Conclusions</p> <p>Because these results suggest that infected mosquitoes may incur fitness costs under natural-like conditions, they are particularly relevant to vector control strategies aiming at boosting naturally occurring refractoriness or spreading natural or foreign genes for refractoriness using genetic drive systems in vector populations.</p

Hydric stress-dependent effects of Plasmodium falciparum infection on the survival of wild-caught Anopheles gambiae female mosquitoes

<p>Abstract</p> <p>Background</p> <p>Whether <it>Plasmodium falciparum</it>, the agent of human malaria responsible for over a million deaths per year, causes fitness costs in its mosquito vectors is a burning question that has not yet been adequately resolved. Understanding the evolutionary forces responsible for the maintenance of susceptibility and refractory alleles in natural mosquito populations is critical for understanding malaria transmission dynamics.</p> <p>Methods</p> <p>In natural mosquito populations, <it>Plasmodium </it>fitness costs may only be expressed in combination with other environmental stress factors hence this hypothesis was tested experimentally. Wild-caught blood-fed <it>Anopheles gambiae </it>s.s. females of the M and S molecular form from an area endemic for malaria in Mali, West Africa, were brought to the laboratory and submitted to a 7-day period of mild hydric stress or kept with water ad-libitum. At the end of this experiment all females were submitted to intense desiccation until death. The survival of all females throughout both stress episodes, as well as their body size and infection status was recorded. The importance of stress, body size and molecular form on infection prevalence and female survival was investigated using Logistic Regression and Proportional-Hazard analysis.</p> <p>Results</p> <p>Females subjected to mild stress exhibited patterns of survival and prevalence of infection compatible with increased parasite-induced mortality compared to non-stressed females. Fitness costs seemed to be linked to ookinetes and early oocyst development but not the presence of sporozoites. In addition, when females were subjected to intense desiccation stress, those carrying oocysts exhibited drastically reduced survival but those carrying sporozoites were unaffected. No significant differences in prevalence of infection and infection-induced mortality were found between the M and S molecular forms of <it>Anopheles gambiae</it>.</p> <p>Conclusions</p> <p>Because these results suggest that infected mosquitoes may incur fitness costs under natural-like conditions, they are particularly relevant to vector control strategies aiming at boosting naturally occurring refractoriness or spreading natural or foreign genes for refractoriness using genetic drive systems in vector populations.</p

Organomegaly in Mali before and after praziquantel treatment. A possible association with Schistosoma haematobium.

Continuous exposure to schistosome-infested water results in acute and chronic morbidity in all ages. We analysed occurence of organomegaly via ultrasonography and investigated a possible additive effect of dual-dose drug administration in 401 Schistosoma haematobium infected individuals from a highly endemic area in Mali. Mean intensity of infection at baseline (22.0 eggs per 10 ml) was reduced to 0.22 eggs per 10 ml 9 weeks after treatment (both treatments combined). Odds of persistent infection among those given dual-dose treatment was 41% of that in people given single dose (b = 0.41; p = 0.05; 95% CI 0.17-1.00), but after two years, 70.7% of the 157 participants, who completed the survey, were re-infected with no significant difference in prevalence and intensity of infection between treatment groups. Resolution of organomegaly occurred in all age groups after treatment. A novel association between Schistosoma haematobium infection and moderate portal vein enlargement was found in 35% (n: 55). Severe portal vein diameter enlargement was found in 3.2%. After two years, moderate hepatomegaly was present in 50.6%, moderate splenomegaly in 45.6% and moderate portal vein diameter enlargement in 19%. A subsequent dose of PZQ did not provide any additional long-term advantages

Geostatistical Model-Based Estimates of Schistosomiasis Prevalence among Individuals Aged ≤20 Years in West Africa

Schistosomiasis is a parasitic disease caused by a blood fluke that mainly occurs in Africa. Current prevalence estimates of schistosomiasis are based on historical data, and hence might be outdated due to control programs, improved sanitation, and water resources development and management (e.g., construction of large dams and irrigation systems). To help planning, coordination, and evaluation of control activities, reliable schistosomiasis prevalence estimates are needed. We analyzed compiled survey data from 1980 onwards for West Africa, including Cameroon, focusing on individuals aged ≤20 years. Bayesian geostatistical models were implemented based on environmental and climatic predictors to take into account potential spatial clustering within the data. We created the first smooth data-driven prevalence maps for Schistosoma mansoni and S. haematobium at high spatial resolution throughout West Africa. We found that an estimated 50.8 million West Africans aged ≤20 years are infected with schistosome blood flukes. Country prevalence estimates ranged between 0.5% (in The Gambia) and 37.1% (in Liberia) for S. mansoni and between 17.6% (in The Gambia) and 51.6% (in Sierra Leone) for S. haematobium. Our results allow prioritization of areas where interventions are needed, and to monitor and evaluate the impact of control activities

Prevalence of Giardia intestinalis Infection in Schistosomiasis-Endemic Areas in South-Central Mali

Intestinal parasite infections are frequent causes of diarrhea and malnutrition among children in the tropics. Transmission of helminths and intestinal protozoa is intimately connected with conditions of poverty, including inadequate sanitation and hygiene. Concurrent infections with several intestinal pathogens may lead to excess morbidity. Yet, there is a paucity of epidemiological data from Mali. In this study, stool samples from 56 individuals, aged 2–63 years, from Bamako and Niono, south-central Mali were examined for intestinal parasites using stool microscopy. Additionally, stool samples were subjected to a rapid diagnostic test (RDT) and polymerase chain reaction (PCR) for the detection of Cryptosporidium spp. and Giardia intestinalis. The predominant pathogens were Schistosoma mansoni and G. intestinalis with prevalences of 41% and 38%, respectively. Hymenolepis nana was detected in 4% of the participants, while no eggs of soil-transmitted helminths were found. Concurrent infections with G. intestinalis and S. mansoni were diagnosed in 16% of the participants. For the detection of G. intestinalis, PCR was more sensitive (100%) than RDT (62%) and microscopy (48%). As helminth-protozoa coinfections might have important implications for morbidity control programs, future studies should employ diagnostic tools beyond stool microscopy to accurately assess the co-endemicity of giardiasis and schistosomiasis

A Comparative Study of the Spatial Distribution of Schistosomiasis in Mali in 1984–1989 and 2004–2006

Geostatistical maps are increasingly being used to plan neglected tropical disease control programmes. We investigated the spatial distribution of schistosomiasis in Mali prior to implementation of national donor-funded mass chemotherapy programmes using data from 1984–1989 and 2004–2006. The 2004–2006 dataset was collected after 10 years of schistosomiasis control followed by 12 years of no control. We found that national prevalence of Schistosoma haematobium and S. mansoni was not significantly different in 2004–2006 compared to 1984–1989 and that the spatial distribution of both infections was similar in both time periods, to the extent that models built on data from one time period could accurately predict the spatial distribution of prevalence of infection in the other time period. This has two main implications: that historic data can be used, in the first instance, to plan contemporary control programmes due to the stability of the spatial distribution of schistosomiasis; and that a decade of donor-funded mass distribution of praziquantel has had no discernable impact on the burden of schistosomiasis in subsequent generations of Malians, probably due to rapid reinfection

Implementing Preventive Chemotherapy through an Integrated National Neglected Tropical Disease Control Program in Mali

Neglected tropical diseases (NTDs) are a group of chronic infections that affect the poorest group of the populations in the world. There are currently five major NTDs targeted through mass drug treatment in the affected communities. The drug delivery can be integrated to deliver different drug packages as these NTDs often overlap in distribution. Mali is endemic with all five major NTDs. The integrated national NTD control program was implemented through the primary health care system using the community health center workers and the community drug distributors aiming at long-term sustainability. After a pilot start in three regions in 2007 without prior examples to follow on integrated mass drug administration, treatment for the five targeted NTDs was gradually scaled up and reached all endemic districts by 2009, and annual drug coverage in the targeted population has since been maintained at a high level for each of the five NTDs. Around 10 million people received one or more drug treatments each year since 2009. The country is on the way to meet the national objectives of elimination or control of these diseases. The successes and lessons learned in Mali are valuable assets to other countries looking to start similar programs

Segmental Duplication Implicated in the Genesis of Inversion 2Rj of Anopheles gambiae

The malaria vector Anopheles gambiae maintains high levels of inversion polymorphism that facilitate its exploitation of diverse ecological settings across tropical Africa. Molecular characterization of inversion breakpoints is a first step toward understanding the processes that generate and maintain inversions. Here we focused on inversion 2Rj because of its association with the assortatively mating Bamako chromosomal form of An. gambiae, whose distinctive breeding sites are rock pools beside the Niger River in Mali and Guinea. Sequence and computational analysis of 2Rj revealed the same 14.6 kb insertion between both breakpoints, which occurred near but not within predicted genes. Each insertion consists of 5.3 kb terminal inverted repeat arms separated by a 4 kb spacer. The insertions lack coding capacity, and are comprised of degraded remnants of repetitive sequences including class I and II transposable elements. Because of their large size and patchwork composition, and as no other instances of these insertions were identified in the An. gambiae genome, they do not appear to be transposable elements. The 14.6 kb modules inserted at both 2Rj breakpoint junctions represent low copy repeats (LCRs, also called segmental duplications) that are strongly implicated in the recent (∼0.4Ne generations) origin of 2Rj. The LCRs contribute to further genome instability, as demonstrated by an imprecise excision event at the proximal breakpoint of 2Rj in field isolates

Feasibility of Onchocerciasis Elimination with Ivermectin Treatment in Endemic Foci in Africa: First Evidence from Studies in Mali and Senegal

The control of onchocerciasis, or river blindness, is based on annual or six-monthly ivermectin treatment of populations at risk. This has been effective in controlling the disease as a public health problem, but it is not known whether it can also eliminate infection and transmission to the extent that treatment can be safely stopped. Many doubt that this is feasible in Africa. A study was undertaken in three hyperendemic onchocerciasis foci in Mali and Senegal where treatment has been given for 15 to 17 years. The results showed that only few infections remained in the human population and that transmission levels were everywhere below postulated thresholds for elimination. Treatment was subsequently stopped in test areas in each focus, and follow-up evaluations did not detect any recrudescence of infection or transmission. Hence, the study has provided the first evidence that onchocerciasis elimination is feasible with ivermectin treatment in some endemic foci in Africa. Although further studies are needed to determine to what extent these findings can be extrapolated to other areas in Africa, the principle of onchocerciasis elimination with ivermectin treatment has been established