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PH8.7 | PH8.7 | Protozoal and Vector-Borne Disease Pharmacotherapy — SDL Guide — SDL Guide (Part 3)

Clinical Decision-Making: Cross-Cutting Issues

Several clinical decision points cut across all four disease categories in PH8.7 and require integrated pharmacological reasoning:

G6PD testing before primaquine (and dapsone): G6PD deficiency is X-linked, affecting approximately 10% of Indian males and presenting in varying degrees of severity across different mutations. Before prescribing primaquine for P. vivax radical cure OR dapsone for leprosy, G6PD status must be tested. If G6PD deficiency is confirmed:
- For P. vivax radical cure: use weekly primaquine 0.75mg/kg/week × 8 weeks (modified radical cure — the slower haemolysis rate allows compensatory erythropoiesis, avoiding haemolytic crisis). Monitor haemoglobin weekly.
- For leprosy MDT: substitute dapsone with clofazimine or ofloxacin (as covered in the leprosy SDL).

Malaria in pregnancy:
- P. falciparum: quinine + clindamycin in first trimester (artemisinin safety in first trimester not fully established — use only if quinine unavailable and benefits clearly outweigh risks). ACT (artemether-lumefantrine preferred) safe in second and third trimesters — WHO endorses AL for P. falciparum in 2nd/3rd trimester.
- Chloroquine safe throughout pregnancy (for P. vivax blood stage).
- Primaquine contraindicated in pregnancy (haemolytic risk to fetus — fetal G6PD status unknown). Defer radical cure until after delivery.
- Mefloquine: caution in first trimester; no clear teratogenicity but neuropsychiatric risk limits use.

Kala-azar in HIV co-infection: HIV-VL co-infection is increasingly recognised; HIV impairs the cell-mediated immunity needed to control Leishmania → higher treatment failure rates, relapse rates >60%. Standard single-dose L-AmB may be insufficient — combination therapy (L-AmB + miltefosine) or secondary prophylaxis may be required. ART initiation is important — controlling HIV restores CMI. Miltefosine is preferred over antimonials in HIV-VL (less cardiotoxicity, oral route).

Amoebiasis vs Giardia (common clinical diagnostic challenge): Both present with diarrhoea after travel/contaminated water. Metronidazole covers both — but the dosing differs: Giardia: metronidazole 400mg TDS × 5 days OR tinidazole 2g single dose. Amoebic dysentery: metronidazole 750mg TDS × 7–10 days + diloxanide. Distinguishing features: Giardia = pale, greasy, foul-smelling, no blood (small intestine); amoebiasis = bloody mucoid stools (large intestine). Both treated with metronidazole/tinidazole.

Self-Assessment: Protozoal and Vector-Borne Diseases

Test your clinical pharmacology knowledge with these scenarios:

Scenario A: A 30-year-old woman in her second trimester of pregnancy develops P. falciparum malaria (blood film positive, parasitaemia 1.5%). She is conscious and tolerating oral medication. What is the drug of choice?

Discussion: In the second and third trimesters, artemether-lumefantrine (AL) is the WHO-recommended first-line treatment for uncomplicated P. falciparum malaria. ACTs are safe and effective in the 2nd and 3rd trimesters. Quinine + clindamycin is reserved for the first trimester (when AL is not first-line). For severe malaria in any trimester: IV artesunate is used despite first-trimester caution (risk-benefit strongly favours treatment). Primaquine is NOT used in pregnancy (no hypnozoites in P. falciparum; and primaquine is contraindicated in pregnancy for vivax radical cure due to fetal G6PD haemolysis risk).

Scenario B: A 45-year-old man from Bihar presents with 3 months of low-grade fever, progressive abdominal distension (hepatosplenomegaly), cachexia, and pancytopenia. rK39 rapid test for kala-azar is positive. He has no prior treatment history. What is the treatment of choice and its mechanism?

Discussion: Liposomal Amphotericin B (L-AmB) 10mg/kg single IV dose — the national standard for visceral leishmaniasis in India. Mechanism: L-AmB is preferentially phagocytosed by macrophages in the reticuloendothelial system (liver, spleen, bone marrow) — the exact intracellular niche where L. donovani amastigotes reside. Amphotericin B binds leishmanial ergosterol, forming membrane pores → ion leak → parasite death. Liposomal formulation dramatically reduces nephrotoxicity vs conventional amphotericin B. Monitor: infusion reactions (pre-medicate), RFT, electrolytes. Expected: fever resolution in 5–7 days, splenic regression over weeks.

Scenario C: During your rural posting, you screen 50 children in a Bihar village for G6PD deficiency before a filariasis MDA programme that includes primaquine. Eight children (16%) test G6PD deficient. Can the MDA proceed? What drug combinations are safe for G6PD-deficient children?

Discussion: The standard 2-drug MDA for LF is DEC + albendazole (in areas without onchocerciasis). DEC does not cause haemolysis in G6PD-deficient individuals (unlike primaquine and dapsone — it does NOT generate oxidative stress in red cells). Ivermectin + albendazole is also safe in G6PD deficiency. However, note: the newer triple-drug MDA includes ivermectin + DEC + albendazole (NO primaquine). MDA for filariasis does NOT include primaquine — primaquine is used for P. vivax radical cure, not filariasis. The G6PD-deficient children can safely receive the standard filariasis MDA.