IgG1 and IgG4 Antibody Responses to the Anopheles gambiae Salivary Protein gSG6

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Human antibody response to the Anopheles gambiae salivary protein gSG6 has recently emerged as a potentially useful tool for malaria epidemiological studies and for the evaluation of vector control interventions. However, the current understanding of the host immune response to mosquito salivary proteins and of the possible crosstalk with early response to Plasmodium parasites is still very limited. We report here the analysis of IgG1 and IgG4 subclasses among anti-gSG6 IgG responders belonging to Mossi and Fulani from Burkina Faso, two ethnic groups which are known for their differential humoral response to parasite antigens and for their different susceptibility to malaria. The IgG1 antibody response against the gSG6 protein was comparable in the two groups. On the contrary, IgG4 titers were significantly higher in the Fulani where, in addition, anti-gSG6 IgG4 antibodies appeared in younger children and the ratio IgG4/IgG1 stayed relatively stable throughout adulthood. Both gSG6-specific IgG1 and IgG4 antibodies showed a tendency to decrease with age whereas, as expected, the IgG response to the Plasmodium circumsporozoite protein (CSP) exhibited an opposite trend in the same individuals. These observations are in line with the idea that the An. gambiae gSG6 salivary protein induces immune tolerance, especially after intense and prolonged exposure as is the case for the area under study, suggesting that gSG6 may trigger in exposed individuals a Th2-oriented immune response.

Citation: Rizzo C, Ronca R, Lombardo F, Mangano V, Sirima SB, et al. (2014) IgG1 and IgG4 Antibody Responses to the Anopheles gambiae Salivary Protein gSG6 in the Sympatric Ethnic Groups Mossi and Fulani in a Malaria Hyperhendemic Area of Burkina Faso. PLoS ONE 9(4): e96130. doi:10.1371/journal.pone.0096130

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ECOWAS Program to Eradicate Malaria

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QUESTION
Why can I find no mention on your website of the ECOWAS program to eradicate malaria in their countries?

ANSWER
Thanks for bringing up ECOWAS. Since 2011, ECOWAS leaders have signaled a commitment to eradicating malaria in their region by 2015, and pilot programs are already underway in several countries, including Burkina Faso, Nigeria and Ghana. The program has centered on the use of larvicides for control of mosquito populations, thus reducing transmission. In April 2012, ECOWAS signed an agreement with Cuba in order to revitalize joint efforts to eradicate malaria in both West Africa as well as the Caribbean island. Soon after, Venezuela entered the agreement, pledging $20 million to the cause. These funds
will help support the construction of manufacturing facilities for biolarvicides in Nigeria, Cote d’Ivoire and Ghana, among other things.

In August, the Commissioner of ECOWAS emphasized the need for community engagement in the fight against malaria. A road map for measuring future progress was also drawn up by health advisers from the region; the next high-level ministerial meeting to evaluate the program will take place in West Africa, and will likely include Cuban and Venezuealan partners, in December 2012.

WHO recommends that Larviciding is indicated only for vectors which tend to breed in permanent or semi-permanent water bodies that can be identified and treated, and where the density of the human population to be protected is sufficiently high to justify the treatment with relatively short cycles of all breeding places.

Malaria in Africa

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QUESTION

How many in Africa have been affected by Malaria?

ANSWER

In 2010, there were approximately 174 million cases of malaria in Africa. However, some people may present with more than one case of malaria per year (especially young children), so the number of people affected is likely considerably lower. However, 90% of deaths from malaria occur in Africa, and 60% in just six countries: Nigeria, DR Congo, Burkina Faso, Mozambique, Cote d’Ivoire and Mali. The good news is that malaria mortality has dropped by 33% in Africa since 2000, which is a very encouraging trend, though the aim of organizations such as Malaria No More is to fully eliminate deaths from malaria globally by 2015.

Malaria Deaths by Country

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QUESTION

Where are the most deaths of malaria?

ANSWER

Over 90% of the deaths from malaria occur in sub-Saharan Africa, and in children under the age of five. According to the World Health Organisation’s 2011 World Malaria Report, the countries with the five highest numbers of reported malaria deaths for 2010 are (and number of reported deaths): Kenya (26,017 deaths), Democratic Republic of Congo (23,476), Tanzania (15,867), Burkina Faso (9,024) and Uganda (8,431).

However, it is important to note that this indicates the number of reported deaths that were confirmed as malaria; there are other countries in Africa which may have similar levels of malaria mortality but insufficient health infrastructure for accurate diagnosis of cause of death or reporting. Even in countries where reporting levels are high, causes of death are not always accurately determined.

In What Countries is Malaria Found?

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QUESTION

What countries can malaria be found in?

ANSWER

Malaria is found on every continent of the world except Antartica—however, regular transmission every year mainly only occurs in Central and South America, Africa, parts of the Middle East, Asia and parts of Oceania/the Pacific Islands.

The world’s highest areas of malaria prevalence and transmission occur in sub-Saharan Africa, followed by India, south-east Asia (especially the Indo-Pacific islands, such as Papua New Guinea) and parts of Central America and northern South America.

Based on the latest available data, the top five countries reporting the most annual malaria deaths were Kenya, the Democratic Republic of Congo, Cote d’Ivoire and Burkina Faso. However, the top five countries with the highest number of malaria cases per 100,000 members of the population were Guinea, Botswana, Burundi, Zambia and Malawi.

The Solomon Islands have the highest number of malaria cases per 100,000 outside of Africa, followed by Yemen. Note that these statistics are highly dependent on quality of diagnosis, treatment and reporting!

Malaria in Burkina Faso

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QUESTION

(1)What drug is administered in the first 24 hours after malaria symptoms onset. What side effects have this/these drugs.

(2) I it is not possible to reach a treatment facility etc until 7 days after initial chills, fever etc and there are no symptoms remaining other than tiredness what is the drug of choice?. Local people say it is malaria but there is no diagnostic facility near the location until a week has passed.

The person in question is visiting in Burkina Faso where malaria is endemic. Standard anti malaria treatment was taken, but we are told that this is not always effective.

ANSWER

1) In most parts of sub-Saharan Africa, due to the spread of chloroquine-resistant strains of Plasmodium falciparum (the most widespread and deadly form of malaria), the first-line treatment for uncomplicated malaria infection are artemisinin-based combination therapy (ACTs) drugs, which combine artemisinin or a derivative (such as artemether) with another anti-malarial drug.

One very common combination is artemether with lumefantrine, which is often marketed as Coartem. ACTs have few common side effects, and very few severe ones, but mild side effects which are reported include nausea, dizziness, loss of appetite and vomiting. One severe side effect that has been reported is allergic reaction.

2) If a patient has had suspected malaria but seems to have recovered, they should probably present themselves to a clinic or physician for a blood test. This will determine whether the patient is still currently suffering from malaria; if so, they will probably still be treated with Coartem or another ACT as above. If there is no trace of the malaria parasites in the blood, the patient might want to try a rapid diagnostic test which looks for antibodies to the malaria parasite; this will tell them if they did in fact have malaria before. Some tests can also differentiate between Plasmodium falciparum and other forms of malaria.

This is important because if they test positive for P. vivax or P. ovale, there is a possibility that the malaria parasites are still present in the liver, in a dormant form, even once all the parasites are gone from the blood stream. In this case, the patient may want to consider talking to their doctor about taking primaquine, which kills the dormant liver stages of the parasites.

People with G6PD deficiency cannot take primaquine so in some cases a G6PD deficiency test may be required first. If the patient is found to have had Plasmodium falciparum, but no active infection appears in the blood, they should still monitor their health carefully for several weeks, and perhaps take malaria preventative medication such as doxycycline or Malarone; even after symptoms cease, in some cases a small number of P. falciparum parasites can remain in the blood, at concentrations too low to be seen under the microscope, but which can then flare up at a later date and cause symptoms to reappear. This is called recrudescence; once symptoms reappear, the patient should immediately seek a diagnosis from the doctor to confirm it is malaria, and then take treatment.