All about Malaria on International Mosquito Day: Dr Srikant Sharma

1. Q-1. What are mosquito-borne diseases?
   A. Mosquito-borne diseases are those spread by the bite of an infected mosquito. Diseases include Zika virus, West Nile virus, Chikungunya virus, dengue, Japanese encephalitis, and malaria. More than half of the global populations (3.3 Billion) are at risk of these infections. The disease accounts for 17% of the estimated global burden of all infectious diseases. In 2016 malaria alone caused 445,000 deaths.

The maximum flight distance of the Anopheles mosquito is 10-12 km when sugar fed, 4.5kms when blood fed and 3.5kms when starved with an average speed of 1.3km/hr. Can fly vertically 2000meters.

Q-2. What is the history of Mosquito day?
A. August 20, 1897, is the original “Mosquito Day”- so named by Indian Born Surgeon-Major Ronald Ross (1857-1932) of the British Indian Medical Service. He discovered a clear, circular body containing malarial pigment in an Anopheles mosquito that had previously fed on an infected patient, convinced that malaria parasites were growing in the mosquito. In 1902, Ross received the Nobel Prize for discovering the mosquito stages of malaria.

Q-3. What is the National Strategic Plan for malaria elimination in India?
A. The Health Ministry has now released its vision for ridding the country of malaria by 2027, and of eliminating the disease by 2030. To be declared malaria-free, a country has to report zero incidences for at least three years. The same hope is for HIV by 2030 and TB by 2025. The ambitious National Strategic Plan (NSP) for Malaria Elimination (2017-22) was launched. Several countries have eliminated malaria, it is possible in India too, but meeting 2027 deadline is an uphill task. Annual Funds allocated for elimination Malaria to National Vector Borne Diseases Control Programme (NVBDCP) in India, in the year 2017-18 stood at Rs.468.5 crores.

Q-4. What is Malaria?
A. Malaria is a serious and sometimes fatal disease caused by a parasite transmitted by vector Anopheles mosquito, who feeds on humans. Symptoms of malaria include fever with shaking chills, arthralgia, malaise, fatigue. A paroxysm of fever, shaking chills, and sweats (every 48 or 72 hours). Less common symptoms are anorexia, lethargy, nausea, vomiting, diarrhea, and jaundice. Most patients have no specific physical finding but splenomegaly may be present.

Q-5. What causes Malaria?
A. Malaria is caused by the Plasmodium parasite and is transmitted by female Anopheles mosquitoes which bite between dusk and dawn. There are 5 different types of parasites that infect humans: P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. Of these, P. falciparum and P. vivax are the most prevalent, and P. falciparum is the most dangerous, with the highest rates of complications and mortality. Plasmodium knowlesi is a malaria parasite that is found in nature in long-tailed and pig-tailed macaques. Naturally acquired human infections were thought to be extremely rare until a large focus of human infections was reported in 2004 in Sarawak, Malaysian Borneo. Human infections have since been described throughout Southeast Asia.

Q-6. How soon will a person feel sick after being bitten by an infected mosquito?
A. For most people, symptoms begin 10 days to 4 weeks after infection, although a person may feel ill as early as 7 days or as late as 1 year later. Two kinds of malaria, P. vivax, and P. ovale can occur again (relapsing malaria). In P. vivax and P. ovale infections, some parasites can remain dormant in the liver for several months up to about 3 years after a person is bitten by an infected mosquito. When these parasites come out of hibernation and begin invading red blood cells (“relapse”), the person will become sick.

Q-7. What is severe Malaria?

A. In severe malaria, clinical or laboratory evidence shows signs of vital organ dysfunction. Symptoms of severe malaria include fever and chills, with impaired consciousness, convulsions, respiratory distress, abnormal bleeding, hypotension, clinical jaundice and evidence of vital organ dysfunction. Severe malaria can be fatal without treatment.
By laboratory parameters, severe malaria is diagnosed if the following are present - base defecit >8meq/l, plasma bicarbonate <15, lactate >5, plasma glucose <40mg/dl, Hb <7g/l, Serum creatinine >3mg/dl, Urea >20mM, Serum bilirubin >3mg/dl, spO2 <92% on room air , coagulation abnormalities, blood parasite level100,000/microL,>10%erythrocytes infected,>5% of neutrophils are with malarial pigments.

Q-8. Is Malaria preventable?
A. Yes. WHO recommends protection for all people at risk of malaria with effective malaria vector control. Two forms of vector control – insecticide (Pyrethroids)-treated mosquito nets and indoor residual spraying (IRS) – are effective in a wide range of circumstances.
Recent studies have suggested that the rise of pyrethroid resistance may undermine the effectiveness of nets. To help manage resistance, some net products incorporate piperonyl butoxide (PBO) along with a pyrethroid insecticide.
IRS involves coating the walls and other surfaces of a house with a residual insecticide. For several months, the insecticide will kill mosquitoes and other insects that come in contact with these surfaces. Wettable powder (WP) formulations are used for indoor residual sprays while emulsion concentrate (EC) formulations are used for larval control. For IRS insecticides in use are DDT 50% WP, malathion 25% WP and synthetic Pyrethroid (WP). This effect is short on porous mud walls, oil painted woods and alkaline whitewash. These mosquitoes hide in vacant space like below the bed, behind cupboards, in dark corners and hence the IRS.
Personal protective measures such as insect repellent, long sleeves, long pants, sleeping in a mosquito-free netting must also be used. Light colored clothes are less attractive for these mosquitoes, hence can be chosen to wear. Circulating air like with fan deter mosquitoes to some extent. Avoid leaving any stagnant water (where mosquito can breed ) around us. Avoid going to crowded areas.
Also used as anti-malarial interventions is Gambusia fish which is placed in standing water to feed on mosquito larvae. Initially though, as creating a long-lasting protection, did not deliver, and their use was progressively restricted to particular ecosystemic situations.

Q-9. Is there any vaccine available to prevent malaria?
A. In November 2016, WHO announced that the vaccine would be rolled out in pilot projects in selected areas in 3 countries in sub-Saharan Africa: Ghana, Kenya, and Malawi. Funding has been secured for the initial phase of the programme and vaccinations are due to begin in 2018. Mosquirix (RTS, S) is a recombinant, adjuvant(ASO1) vaccine that is given to children aged 6 weeks to 17 months (first dose) to help protect against malaria caused by the parasite Plasmodium falciparum. Three doses, each of 0.5 ml, should be given at monthly intervals. - A fourth dose is recommended 18 months after the third dose. Its efficacy is from 25% to 50% in infants and young children respectively.
RTS, S is designed to prevent the malaria parasite from infecting, maturing and multiplying in the liver. RTS, S is a scientific name representing its composition as R stands for the central repeat region of Plasmodium falciparum(circumsporozoite protein-CSP), T for the T cell epitopes of the CSP, S for the hepatitis B surface antigen. They are combined in a single fusion protein (RTS)and Co-expressed in yeast cells with free HBsAg. The RTS fusion protein and free S protein spontaneously assembly in RTS, S particles.

Q-10. How much is the disease burden?
A. According to the latest World Malaria Report, released in November 2017, there were 216 million cases of malaria in 2016, up from 211 million cases in 2015. The estimated number of malaria deaths stood at 4,45,000 in 2016, a similar number to the previous year (4,46,000). India accounted for 6% of all malaria cases in the world, 6% of the deaths, and 51% of the global P. vivax cases. The Report estimates the total cases in India is 1.31 million (0.94-1.83 million) and deaths at 23990.

Q-11. What areas in India are affected by malaria?
A. All areas throughout the country, including cities like Mumbai and Delhi, except none in areas >2,000 m (6,562 ft) in Himachal Pradesh, Jammu and Kashmir, and Sikkim.

Q-12. How to test for Malaria?
A. Thick and thin blood smears.
Thick film is performed for seeing the presence and count of parasites. A thin blood smear is performed to know the species of malaria. Also, the thin film is performed when more than 100 parasites in each thick film are seen, which corresponds to more than 18000 parasites per microliter of blood. This test is the gold standard and has the highest sensitivity.

Rapid diagnostic test(RDT) or antigen testing, this is a quick option when blood draws and smears aren't available.
RDT’s are less effective when parasite levels are below 100 parasites/ml. Hence a second the screening test is often required to confirm.

Polymerase chain reaction assay test
Parasite nucleic acids are detected using polymerase chain reaction (PCR). Although this technique may be slightly more sensitive than smear microscopy, it is of limited utility for the diagnosis of acutely ill patients in the standard healthcare setting. PCR results are often not available quickly enough to be of value in establishing the diagnosis of malaria infection.
PCR is most useful for confirming the species of malarial parasite after the diagnosis has been established by either smear microscopy or RDT.
The sensitivity of Thick smear is 98.36%, Thin smear 72.45% and for antigen detection method it was 92.13%. (J. Pathology and Oncology 2017)

Q-13. What about immune-suppressed patients (HIV) who get infected with Malaria?
A. In areas with stable malaria transmission, HIV increases the risk of malaria infection and clinical malaria in adults, especially in those with advanced immunosuppression. In settings with unstable malaria transmission, HIV-infected adults are at increased risk of complicated and severe malaria and death.
Reports also suggest that anti-malarial treatment failure may be more common in HIV-infected adults with low CD4-cell counts compared to those not infected with HIV.

Q-14. Is malaria contagious?
A. No, the mosquito is the vector that transmits the disease. Malaria does not spread from person to person like a cold or flu, and it cannot be sexually transmitted.

Q-15. Are malarial treated patients protected from malaria in the future?
A. No, anyone who goes to a malaria‐risk country should take precautions against contracting malaria. Usually, people who live in malaria‐endemic areas have some immunity to malaria. However, without frequent exposure to malaria parasites, your immune system loses its ability to fight malaria. You are as much at risk as a non-immune person.

Q-16. Is it considered safe to breastfeed while taking anti-malarial drugs?
A. There are limited data available about the safety of anti-malarial drugs while breastfeeding. However, the amount of anti-malarial drug transferred from the nursing mother to her infant is not thought to be harmful to the infant.

Q-17. How does Malaria affect pregnant ladies?
A. Malaria can increase the risk for serious pregnancy problems, including prematurity, miscarriage, and stillbirth. If travel to a malarious area cannot be postponed, use of an effective chemoprophylaxis regimen is essential.

Q-18. Is there any genetic resistance to Malaria?
A. Yes, G6PD deficiency, several Hb mutations (hemoglobinopathies) and ovalocytosis (a molecular defect of band 3 protein in the human RBC) are protective against P.falciparum malaria and in several cases also against vivax malaria.

Q-19. Can one donate blood if affected from Malaria?
A. In general, most travelers to an area with malaria are deferred from donating blood for 1 year after their return. People who used to live in countries where malaria transmission occurs cannot donate blood for 3 years. People diagnosed with malaria cannot donate blood for 3 years after
treatment, during which time they must have remained free of symptoms of malaria.

Q-20. What is the recommendation for treatment of malaria?
A. Prompt treatment within 24 hours of fever onset with an effective and safe antimalarial is necessary to effect a cure and prevent life-threatening complications.
Chloroquine is the drug of choice for P. Vivax Malaria.

Artemisinin-based combination therapies (ACTs) are recommended by WHO as the first and second-line treatment for uncomplicated P. falciparum malaria as well as for chloroquine-resistant P. vivax malaria. ACTs combine an artemisinin derivative with a partner drug. The role of the artemisinin compound is to reduce the number of parasites during the first 3 days of treatment (reduction of parasite biomass), while the role of the partner drug is to eliminate the remaining parasites (cure).
ACT combinations with long half‐lives probably also provide a longer prophylactic effect after treatment, with significantly fewer recurrent parasitaemias. Efficacy is determined by the drug partnering the artemisinin derivative and, for artesunate-mefloquine, artemether-lumefantrine, and dihydroartemisinin-piperaquine, this usually exceeds 95%. Artesunate–sulfadoxine–pyrimethamine and artesunate-amodiaquine are effective in some areas, but in other areas, resistance to the partner precludes their use. Parenteral Artesunate is the drug of choice in severe P. Falciparum and P. Vivax cases. Quinine is an acceptable alternative therapy.

Q-21. What is known about Artemisinin resistance?
A. Artemisinin resistance typically refers to a delay in the clearance of malaria parasites from the bloodstream following treatment with an ACT. As a result, the artemisinin compound is less effective in clearing all parasites within a 3-day period among patients who are infected with artemisinin-resistant strains of malaria.

Q-22. What is the treatment in the case of a pregnant female patient?
A. The First Trimester – Parenteral Quinine is the drug of choice. If it is not available, parenteral artemisinin derivatives can be given to save the life of the mother.
Second and third trimester – Parenteral Artemisinin derivatives - Artesunate is the drug of choice.
Q-23. What is single dose treatment for malaria?
A. The FDA has approved a new drug Krintafel (Tafenoquine) for the treatment of malaria. This drug is developed by GSK pharmaceuticals and medicines for malaria venture. This drug is meant for people who’ve had malaria before caused by Plasmodium vivax. Currently, patients with P. vivax require a 10-day treatment with the drug primaquine.

Q-24. What can one take for prophylaxis of Malaria?
A. Doxycycline: 100mg/day(1.5mg/kg of body weight per day) to be started 2 days before and continued 4 weeks after leaving a malarious area. It is not recommended for pregnant and lactating women and children below 8 years of age. This is recommended for people traveling to south-east Asia, along with the borders of Thailand and Cambodia / Burma.

Mefloquine: 250mg weekly(5mg/kg of body weight/week) to be started 2 weeks before going to the affected area and continued for 4 weeks after leaving the affected area. This drug can be used in most parts of the world.

Chloroquine: 300mg weekly. To be started 1 week before travel up to 4 weeks after. The only areas where chloroquine-sensitive falciparum malaria still occurs include Haiti, some rural parts of Mexico and Central America, and some rural part of the Middle East.
Recommended drugs for each country varies for chemoprophylaxis. No antimalarial drug is 100% protective; therefore, prophylaxis must be combined with the use of personal protective measures.

Q-25. What are the bad prognostic factors of Malaria?
A. Anemia, hypoglycemia, coma, convulsion, organ dysfunction, lactic acidosis hyperparasitemia, and leucocytosis are the prognostic factors in severe and complicated malaria as defined by WHO. Out of these, the worst outcome is for patients who suffer from organ dysfunction and lactic acidosis.

Q-26. What is the mortality rate of malaria with respect to bad prognostic outcomes?
A. Cerebral malaria has a mortality rate of up to 50%. Acute Renal Failure has a mortality of 15- 45%. Almost all deaths (99%) resulted from P. falciparum malaria. Plasmodium vivax is estimated to have been responsible for 3100 deaths in 2015 (range: 1800–4900), with most (86%) occurring outside Africa. In 2015, 303 000 malaria deaths (range: 165 000–450 000) were estimated to have occurred in children aged under 5 years, equivalent to 70% of the global total.

Q-27. Is Malaria a notifiable disease?
A. Yes, it is a notifiable disease in India. The notification stipulates better case management and reduces the transmission of disease. Health care providers should notify every case to the district medical and health officer daily. An appropriate strategy for control of mosquitoes breeding could then be devised. Since its primarily a preventable disease, hence notification may help in reducing the disease propagation if proper and prompt action is initiated.

Q-28. What to do after recovery from malaria?

A. Immuno-suppression may increase the risk of malaria infection and clinical malaria in adults. In settings with unstable malaria transmission, immunosuppressive adults are at increased risk of complicated and severe malaria and death. Hence post recovery person should follow the healthy balanced diet with high protein, high red and yellow fruits, and high mineral, high dry fruits diets. They should do daily exercise (150 minutes in at least 5 divided days per week) or Yoga. Avoid pollution, smoking, alcohol. Take a good sleep, and last but not least, positive thinking
which helps to modify the good immunity of the person.

The article has been written by Dr Srikant Sharma, Senior Consultant Medicine along with Dr Nabeela Khan from Moolchand Medicity, New Delhi.