A 12 year old boy with fever and multiple swellings on his limbs. Is it malaria or brucellosis or tuberculosis? First blog.

A young lad about 12 years of age was brought by his father for treatment from their home town of Bahawalpur to Karachi. The boy and his father had slightly different stories to tell and also his father had more information of the treatment received and the opinion of other doctors who had seen the young patient, the examiner’s decided to request the father to stay with the patient to answer the candidates questions, The father had been told not to say anything unless the candidate asked him a direct question.

The history was that he boy had suffered from recurrent episodes of fever for one year. We needed to know why. The young boy had multiple soft mobile swellings just under the skin, One was on the medial aspect of the elbow about 3 inches long and 11/2 inches wide, there was a similar one slightly smaller on the back of the left elbow and one on the scapula. He was emaciated, but otherwise bright. his lymph nodes were not enlarged. His spleen was 3 cm enlarged and was firm. The liver was not enlarged. N one in the close family had tuberculosis and he had not been in known contact with a TB patient in his school. What information was needed to identify the problem and proceed further?

The pattern of the fever was periodic. The father said that the boy got better after 3-4 weeks and went back to school but the fever came back sometimes for a week or ten days. He had received multiple courses of malaria and “typhoid” according to the fever, even IV antibiotics were used. The father gave a history of having bought some animals a year ago. a cow and 5 goats and kept them at home for several months until the Eid sacrifice. During this time the cow needed to be treated by the veterinarian. Only the father gave this history. Both candidates who had this patient as a long case asked if the family lived in the city. When the answer was yes they did not ask for a history of exposure to animals. One candidate chose not to speak to the father at all!!!

If you think of malaria first do remember that you are thinking of non-falciparum malaria. Pl falciparum does not have an exoerythrocytic cycle and there does not cause recurrent or chronic malaria. If a person survives one bout of falciparum malaria they have to be bitten by another mosquito carrying the parasite hence every episode is a “new” one. As there is no persistence of the parasite in the liver the spleen does not enlarge, hence falciparum do not cause hypersplenism or PUO with an enlarged spleen. This is a PASS or FAIL piece of information. Plasmodium vivax is the one which is also endemic in Pakistan. It has a low transmission rate, mosquitos tend to die out in the very cold winters specially in the north of Pakistan and when heavy monsoons wash out breeding areas, hence patients in Pakistan tend to behave as non-immunes so typical bouts of malaria with cold stage,  hot stage, and defervescence with sweating are uncommon until the patient has had fever for up to two weeks allowing the schizonts to develop before the recognisable time sequenced events can be seen, usually before then somebody has given the patient anti malaria therapy often artemether injections as Pakistani GPs do not believe in a lab work up for fever before treatment, You are unlikely to see classical malaria with splenomegaly. This patient has probably received antimalarial therapy several times over so vivax malaria is very unlikely to be the cause. Remember resistance to chloroquine is a problem with Pl falciparum but is not found in every case. Resistance to chloroquine is not common in vivax malaria in Pakistan. We do not have Pl ovale or malariae in Pakistan. You should know all this and mention it if you are asked why you do not think of malaria in this case as the number one diagnosis. Tests that you will do for malaria are blood films for MP repeatedly  which you expect to find negative (mention this), high serum antimalarial antibodies so do a quantitative estimation just a positive Ig-ICT which is not enough, look for polyclonal Ig M hyperglobulinemia and a positive PCR for plasmodial DNA. If you find blood films for MP positive this indicates a recent infection and is not the cause of the massive spleen so look for another cause for it. There may be an underlying lymphoma, leukemia or hemoglobinopathy.

Is this hyperreactive splenomegaly? Hyperreactive malarial splenomegaly (HMS), previously known as tropical splenomegaly syndrome (TSS), is a complication of chronic malaria. The prevalence is high in Eastern Indonesia and Papuan highlands where P. vivax and P. malariae are the predominant species, although it can occur in association with any malaria species. It is uncommon in Pakistan and if you see a PUO with a firm splenomegaly here then look for an underlying congenital haemolytic anemia like spherocytosis or Hb D or Hb Punjab which are common and not just chronic malaria.

HMS occurs as a result of overproduction of IgM secondary to repeated infection, with subsequent formation of immune complexes that cause prolonged stimulation of splenic reticuloendothelial cells. Among patients in Indonesia with HMS and elevated P. vivax antibody titers, antibody overproduction has been linked to a decrease in T-suppressor lymphocytes that normally downregulate B-lymphocyte function and antibody production. Hence there may be a genetic basis for the prevalence of HMS in certain parts of the world.

Clinical manifestations of HMS include left upper quadrant pain, fatigue, ascites, lower extremity edema, and dyspnea; these symptoms become debilitating as the disease progresses. Parasitemia is uncommon; the diagnosis is generally made among long-term residents of malarious areas based on presence of massive splenomegaly, high serum antimalarial antibody levels, and polyclonal Ig M hypergammaglobulinemia and PCR amplification of plasmodial DNA in the absence of parasitemia. Demonstration of malaria infection correlates with treatment success.

How will you mange a case of proven HMS?

Treatment of hyperreactive splenomegaly consists of antimalarial therapy for the duration of ongoing malaria exposure. Chloroquine (300 mg base [= 500 mg salt]) once weekly is effective in reducing spleen size and symptoms over several months in 70 to 80 percent of cases. if the patient cannot leave the area where malaria is prevent, then prohylactic treatment may be required for life. In areas with known chloroquine resistance, alternative agents should be used for initial treatment followed by prophylactic doses. Splenectomy carries an appreciable risk of mortality and so should only be considered as a treatment for severely debilitating massive splenomegaly unresponsive to medical management.

Read up the treatment for chloroquine responsive malaria (the good old 10 tablets of Resochin 6 tablets stat, 2 after 6 hours and 1+1 for two days) which all your examiners have used, treatment for malaria resistant to chloroquine and treatment of complicated malaria. Any third world physician who does not understand clinical malaria and its treatment cannot expect to pass and has no right to expect to pass. Malaria and typhoid fever are the two most over-diagnosed and improperly treated diseases in this country (Pakistan).

In my follow on blog I will discuss two more infectious causes of fever with a large spleen Brucellosis and tuberculosis.


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I am a Professor of Medicine and a Nephrologist. Having served in the Army Medical College, Pakistan Army for 27 years I eventually became the Dean and Principal of the Bahria University Medical and Dental College Karachi from where I retired in 2016. My passion is teaching and mentoring young doctors. I am associated with the College of Physicians and Surgeons Pakistan as a Fellow and an examiner. I find that many young doctors make mistakes because they do not understand how they should answer questions; basically they do not understand why a question is being asked. My aim is to help them process the information they acquire as part of their education to answer questions, pass examinations and to best take care of patients without supervision of a consultant. Read my blog, interact and ask questions so that I can help you more.

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