Oral Primaquine Research Articles

Primaquine radical cure in patients with Plasmodium falciparum malaria in areas co-endemic for P falciparum and Plasmodium vivax (PRIMA): a multicentre, open-label, superiority randomised controlled trial

In areas co-endemic for Plasmodium vivax and Plasmodium falciparum there is an increased risk of P vivax parasitaemia following P falciparum malaria. Radical cure is currently only recommended for patients presenting with P vivax malaria. Expanding the indication for radical cure to patients presenting with P falciparum malaria could reduce their risk of subsequent P vivax parasitaemia. We did a multicentre, open-label, superiority randomised controlled trial in five health clinics in Bangladesh, Indonesia, and Ethiopia. In Bangladesh and Indonesia, patients were excluded if they were younger than 1 year, whereas in Ethiopia patients were excluded if they were younger than 18 years. Patients with uncomplicated P falciparum monoinfection who had fever or a history of fever in the 48 h preceding clinic visit were eligible for enrolment and were required to have a glucose-6-dehydrogenase (G6PD) activity of 70% or greater. Patients received blood schizontocidal treatment (artemether-lumefantrine in Ethiopia and Bangladesh and dihydroartemisinin-piperaquine in Indonesia) and were randomly assigned (1:1) to receive either high-dose short-course oral primaquine (intervention arm; total dose 7 mg/kg over 7 days) or standard care (standard care arm; single dose oral primaquine of 0·25 mg/kg). Random assignment was done by an independent statistician in blocks of eight by use of sealed envelopes. All randomly assigned and eligible patients were included in the primary and safety analyses. The per-protocol analysis excluded those who did not complete treatment or had substantial protocol violations. The primary endpoint was the incidence risk of P vivax parasitaemia on day 63. This trial is registered at ClinicalTrials.gov, NCT03916003. Between Aug 18, 2019, and March 14, 2022, a total of 500 patients were enrolled and randomly assigned, and 495 eligible patients were included in the intention-to-treat analysis (246 intervention and 249 control). The incidence risk of P vivax parasitaemia at day 63 was 11·0% (95% CI 7·5-15·9) in the standard care arm compared with 2·5% (1·0-5·9) in the intervention arm (hazard ratio 0·20, 95% CI 0·08-0·51; p=0·0009). The effect size differed with blood schizontocidal treatment and site. Routine symptom reporting on day 2 and day 7 were similar between groups. In the first 42 days, there were a total of four primaquine-related adverse events reported in the standard care arm and 26 in the intervention arm; 132 (92%) of all 143 adverse events were mild. There were two serious adverse events in the intervention arm, which were considered unrelated to the study drug. None of the patients developed severe anaemia (defined as haemoglobin <5 g/dL). In patients with a G6PD activity of 70% or greater, high-dose short-course primaquine was safe and relatively well tolerated and reduced the risk of subsequent P vivax parasitaemia within 63 days by five fold. Universal radical cure therefore potentially offers substantial clinical, public health, and operational benefits, but these benefits will vary with endemic setting. Australian Academy of Science Regional Collaborations Program, Bill & Melinda Gates Foundation, and National Health and Medical Research Council.

Supervised versus unsupervised primaquine radical cure for the treatment of falciparum and vivax malaria in Papua, Indonesia: a cluster-randomised, controlled, open-label superiority trial

SummaryBackgroundThere is a high risk of Plasmodium vivax recurrence in patients treated for Plasmodium falciparum malaria in co-endemic areas. Primaquine radical cure has the potential to reduce P vivax recurrences in patients presenting with P falciparum as well as P vivax malaria but is undermined by poor adherence to the currently recommended 14-day regimen. We aimed to assess the efficacy and safety of supervised versus unsupervised primaquine radical cure in patients presenting with uncomplicated malaria.MethodsWe did a cluster-randomised, controlled, open-label superiority trial in Papua, Indonesia. 21 clusters of village health posts, matched by annual parasite index, were randomly assigned (1:1) to treat patients (age >12 months and body weight >5 kg) presenting with confirmed uncomplicated P falciparum or P vivax malaria with oral dihydroartemisinin–piperaquine plus either a supervised or unsupervised 14-day course of oral primaquine (0·5 mg/kg per day). Patients in the supervised group were supervised taking their primaquine dose on alternate days. Patients were followed-up for 6 months and those who presented again with malaria were retreated with the same drug regimen. Masking was not possible due to the nature of the study. The primary outcome was the incidence risk of P vivax malaria over 6 months, assessed in the modified intention-to-treat population (all patients who were assigned to a treatment group, excluding patients who were lost to follow-up after their first visit). This trial is now complete, and is registered with ClinicalTrials.gov, NCT02787070.FindingsBetween Sept 14, 2016, and July 31, 2018, 436 patients were screened for eligibility and 419 were enrolled; 223 (53%) patients in 11 clusters were assigned to supervised primaquine treatment and 196 (47%) in ten clusters to unsupervised primaquine treatment. 161 (72%) of 223 patients in the supervised group and 151 (77%) of 196 in the unsupervised group completed 6 months of follow-up. At 6 months, the incidence risk of P vivax recurrence in the supervised group was 29·7% (95% CI 16·4–49·9) versus 55·8% (32·3–81·8) in the unsupervised group (hazard ratio 0·23 [95% CI 0·07–0·76]; p=0·016). The incidence rate for P vivax recurrence was 539 (95% CI 390–747) infections per 1000 person-years in the supervised group versus 859 (673–1096) in the unsupervised group (incidence rate ratio 0·63 [95% CI 0·42–0·94]; p=0·025). The corresponding rates in the 224 patients who presented with P falciparum malaria were 346 (95% CI 213–563) and 660 (446–977; incidence rate ratio 0·52 [95% CI 0·28–0·98]; p=0·043). Seven serious adverse events were reported (three in the supervised group, four in the unsupervised group), none of which were deemed treatment-related, and there were no deaths.InterpretationIn this area of moderate malaria transmission, supervision of primaquine radical cure treatment reduced the risk of P vivax recurrence. This finding was apparent for patients presenting with either P falciparum or P vivax malaria. Further studies are warranted to investigate the safety and efficacy of radical cure for patients presenting with uncomplicated falciparum malaria in other co-endemic areas.FundingThe Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Foreign Affairs and Trade of the Australian Government.TranslationFor the Indonesian translation of the abstract see Supplementary Materials section.

Arterolane–piperaquine–mefloquine versus arterolane–piperaquine and artemether–lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a single-centre, open-label, randomised, non-inferiority trial

SummaryBackgroundTriple antimalarial combination therapies combine potent and rapidly cleared artemisinins or related synthetic ozonides, such as arterolane, with two, more slowly eliminated partner drugs to reduce the risk of resistance. We aimed to assess the safety, tolerability, and efficacy of arterolane–piperaquine–mefloquine versus arterolane–piperaquine and artemether–lumefantrine for the treatment of uncomplicated falciparum malaria in Kenyan children.MethodsIn this single-centre, open-label, randomised, non-inferiority trial done in Kilifi County Hospital, Kilifi, coastal Kenya, children with uncomplicated Plasmodium falciparum malaria were recruited. Eligible patients were aged 2–12 years and had an asexual parasitaemia of 5000–250 000 parasites per μL. The exclusion criteria included the presence of an acute illness other than malaria, the inability to tolerate oral medications, treatment with an artemisinin derivative in the previous 7 days, a known hypersensitivity or contraindication to any of the study drugs, and a QT interval corrected for heart rate (QTc interval) longer than 450 ms. Patients were randomly assigned (1:1:1), by use of blocks of six, nine, and 12, and opaque, sealed, and sequentially numbered envelopes, to receive either arterolane–piperaquine, arterolane–piperaquine–mefloquine, or artemether–lumefantrine. Laboratory staff, but not the patients, the patients' parents or caregivers, clinical or medical officers, nurses, or trial statistician, were masked to the intervention groups. For 3 days, oral artemether–lumefantrine was administered twice daily (target dose 5–24 mg/kg of bodyweight of artemether and 29–144 mg/kg of bodyweight of lumefantrine), and oral arterolane–piperaquine (arterolane dose 4 mg/kg of bodyweight; piperaquine dose 20 mg/kg of bodyweight) and oral arterolane–piperaquine–mefloquine (mefloquine dose 8 mg/kg of bodyweight) were administered once daily. All patients received 0·25 mg/kg of bodyweight of oral primaquine at hour 24. All patients were admitted to Kilifi County Hospital for at least 3 consecutive days and followed up at day 7 and, thereafter, weekly for up to 42 days. The primary endpoint was 42-day PCR-corrected efficacy, defined as the absence of treatment failure in the first 42 days post-treatment, of arterolane–piperaquine–mefloquine versus artemether–lumefantrine, and, along with safety, was analysed in the intention-to-treat population, which comprised all patients who received at least one dose of a study drug. The 42-day PCR-corrected efficacy of arterolane–piperaquine–mefloquine versus arterolane–piperaquine was an important secondary endpoint and was also analysed in the intention-to-treat population. The non-inferiority margin for the risk difference between treatments was −7%. The study is registered in ClinicalTrials.gov, NCT03452475, and is completed.FindingsBetween March 7, 2018, and May 2, 2019, 533 children with P falciparum were screened, of whom 217 were randomly assigned to receive either arterolane–piperaquine (n=73), arterolane–piperaquine–mefloquine (n=72), or artemether–lumefantrine (n=72) and comprised the intention-to-treat population. The 42-day PCR-corrected efficacy after treatment with arterolane–piperaquine–mefloquine (100%, 95% CI 95–100; 72/72) was non-inferior to that after treatment with artemether–lumefantrine (96%, 95% CI 88–99; 69/72; risk difference 4%, 95% CI 0–9; p=0·25). The 42-day PCR-corrected efficacy of arterolane–piperaquine–mefloquine was non-inferior to that of arterolane–piperaquine (100%, 95% CI 95–100; 73/73; risk difference 0%). Vomiting rates in the first hour post-drug administration were significantly higher in patients treated with arterolane–piperaquine (5%, 95% CI 2–9; ten of 203 drug administrations; p=0·0013) or arterolane–piperaquine–mefloquine (5%, 3–9; 11 of 209 drug administrations; p=0·0006) than in patients treated with artemether–lumefantrine (1%, 0–2; three of 415 drug administrations). Upper respiratory tract complaints (n=26 for artemether–lumefantrine; n=19 for arterolane–piperaquine–mefloquine; n=23 for arterolane–piperaquine), headache (n=13; n=4; n=5), and abdominal pain (n=7; n=5; n=5) were the most frequently reported adverse events. There were no deaths.InterpretationThis study shows that arterolane–piperaquine–mefloquine is an efficacious and safe treatment for uncomplicated falciparum malaria in children and could potentially be used to prevent or delay the emergence of antimalarial resistance.FundingUK Department for International Development, The Wellcome Trust, The Bill & Melinda Gates Foundation, Sun Pharmaceutical Industries

An Unusual Case of Concurrent Dengue and Malaria Infection

Dengue and malaria infections are common mosquito-borne infectious diseases in tropical and subtropical regions. The clinical manifestations of dengue and malaria often mimic each other, causing the predicament of early diagnosis without laboratory investigations. Concurrent dengue and malaria infection are often rare scenarios when both diseases occur in a particular patient at the same time. A high index of suspicion is therefore required to establish an early diagnosis to ensure complete success in its management. This case report is about concurrent dengue and malaria infection in a 54-year-old Pakistani man who presented with high-grade fever for three days before admission. On examination, he was febrile (38.8°C) with no other findings. His blood investigations were positive for NS1 antigen and IgM but negative for IgG. His peripheral blood film revealed the presence of Plasmodium vivax. He was treated for dengue fever with supportive management and started with oral Riamet (artemether and lumefantrine) along with oral primaquine 30 mg daily for two weeks’ duration. Following treatment, the patient demonstrated progressive clinical improvement and was subsequently discharged back to the community clinic for the continuation of care.

A successful therapy for severe malaria accompanied by malaria-related acute kidney injury (MAKI) complications: a case report

Indonesia is an endemic malaria country with high levels of morbidity and mortality. In Aceh, by the end of 2016, based on the data from Annual Parasite Incidence, the incidence rate was 0.1 per 1.000 population at risk of malaria. One of severe malaria complications is malaria-related acute kidney injury(MAKI). The death increasesthreefold by the presence of MAKI. A 56 years old male farmer was a resident in Buketmeuh village, Meukek, South Aceh, Indonesia, which was an endemic malaria area. He hadfever for seven days, chills, sweating, joint pain, headache, nausea, vomit, yellow eyes and raved. Concentrated tea-colored urineduring four days before hospital admission with a small amount of urine of 200 cc in 24 hours. The diagnosis established based on the Plasmodium vivax trophozoite finding in the blood smear examination, and the severe malaria clinical descriptions such as black water fever (BWF)with MAKI complications. Artemether injection therapy followed by oral primaquine, dihydroartemisinin and piperaquine phosphate (DHP) and hemodialysis provide a good outcome.

Chloroquine Resistance in a Case with Uncomplicated Plasmodium vivax Malaria: An Evolving Threat

Introduction: Chloroquine resistance is an emerging phenomenon in uncomplicated Plasmodium vivax malaria. Presentation of Case: This case report describes a 21 year old forest worker who was diagnosed to have Plasmodium vivax malaria on blood film microscopy and it was confirmed on molecular real-time polymerase chain reaction analysis. He was treated with conventional oral chloroquine of optimal dosage in which he failed to respond appropriately. His blood film parasite count increased on day 3 of treatment despite adequate chloroquine therapy. He was then commenced on oral artemether-lumefantrine (Riamet) combination therapy in which he responded clinically and microscopically. He was discharged from the hospital after completing a 14-day course of oral primaquine. His serial blood films were negative for more than three consecutive days whilst in hospital. On subsequent weekly follow ups at the specialist clinic for a duration of 28 days, his blood films remained negative for malaria parasites. Conclusion: Chloroquine resistance is now an emerging threat in many middle and low income countries globally. Case Study Kasinathan; BJAST, 13(2): 1-4, 2016; Article no.BJAST.22553 2

Pharmacokinetics and pharmacodynamics of (+)-primaquine and (-)-primaquine enantiomers in rhesus macaques (Macaca mulatta).

Primaquine (PQ) remains the sole available drug to prevent relapse of Plasmodium vivax malaria more than 60 years after licensure. While this drug was administered as a racemic mixture, prior studies suggested a pharmacodynamic advantage based on differential antirelapse activity and/or toxicities of its enantiomers. Oral primaquine enantiomers prepared using a novel, easily scalable method were given for 7 days to healthy rhesus macaques in a dose-rising fashion to evaluate their effects on the blood, liver, and kidneys. The enantiomers were then administered to Plasmodium cynomolgi-infected rhesus macaques at doses of 1.3 and 0.6 mg/kg of body weight/day in combination with chloroquine. The (-)-PQ enantiomer had higher clearance and apparent volume of distribution than did (+)-PQ and was more extensively converted to the carboxy metabolite. There is evidence for differential oxidative stress with a concentration-dependent rise in methemoglobin (MetHgb) with increasing doses of (+)-PQ greater than that seen for (-)-PQ. There was a marked, reversible hepatotoxicity in 2 of 3 animals dosed with (-)-PQ at 4.5 mg/kg. (-)-PQ in combination with chloroquine was successful in preventing P. cynomolgi disease relapse at doses of 0.6 and 1.3 mg/kg/day, while 1 of 2 animals receiving (+)-PQ at 0.6 mg/kg/day relapsed. While (-)-PQ was also associated with hepatotoxicity at higher doses as seen previously, this has not been identified as a clinical concern in humans during >60 years of use. Limited evidence for increased MetHgb generation with the (+) form in the rhesus macaque model suggests that it may be possible to improve the therapeutic window for hematologic toxicity in the clinic by separating primaquine into its enantiomers.

Assessment of the prophylactic activity and pharmacokinetic profile of oral tafenoquine compared to primaquine for inhibition of liver stage malaria infections

BackgroundAs anti-malarial drug resistance escalates, new safe and effective medications are necessary to prevent and treat malaria infections. The US Army is developing tafenoquine (TQ), an analogue of primaquine (PQ), which is expected to be more effective in preventing malaria in deployed military personnel.MethodsTo compare the prophylactic efficacy of TQ and PQ, a transgenic Plasmodium berghei parasite expressing the bioluminescent reporter protein luciferase was utilized to visualize and quantify parasite development in C57BL/6 albino mice treated with PQ and TQ in single or multiple regimens using a real-time in vivo imaging system (IVIS). As an additional endpoint, blood stage parasitaemia was monitored by flow cytometry. Comparative pharmacokinetic (PK) and liver distribution studies of oral and intravenous PQ and TQ were also performed.ResultsMice treated orally with three doses of TQ at 5 mg/kg three doses of PQ at 25 mg/kg demonstrated no bioluminescence liver signal and no blood stage parasitaemia was observed suggesting both drugs showed 100% causal activity at the doses tested. Single dose oral treatment with 5 mg TQ or 25 mg of PQ, however, yielded different results as only TQ treatment resulted in causal prophylaxis in P. berghei sporozoite-infected mice. TQ is highly effective for causal prophylaxis in mice at a minimal curative single oral dose of 5 mg/kg, which is a five-fold improvement in potency versus PQ. PK studies of the two drugs administered orally to mice showed that the absolute bioavailability of oral TQ was 3.5-fold higher than PQ, and the AUC of oral TQ was 94-fold higher than oral PQ. The elimination half-life of oral TQ in mice was 28 times longer than PQ, and the liver tissue distribution of TQ revealed an AUC that was 188-fold higher than PQ.ConclusionsThe increased drug exposure levels and longer exposure time of oral TQ in the plasma and livers of mice highlight the lead quality attributes that explain the much improved efficacy of TQ when compared to PQ.

Antiparasitic Therapy

Parasitic diseases affect more than 2 billion people globally and cause substantial morbidity and mortality, particularly among the world's poorest people. This overview focuses on the treatment of the major protozoan and helminth infections in humans. Recent developments in antiparasitic therapy include the expansion of artemisinin-based therapies for malaria, new drugs for soil-transmitted helminths and intestinal protozoa, expansion of the indications for antiparasitic drug treatment in patients with Chagas disease, and the use of combination therapy for leishmaniasis and human African trypanosomiasis.

Clinical and parasitological response to oral chloroquine and primaquine in uncomplicated human Plasmodium knowlesi infections

BackgroundPlasmodium knowlesi is a cause of symptomatic and potentially fatal infections in humans. There are no studies assessing the detailed parasitological response to treatment of knowlesi malaria infections in man and whether antimalarial resistance occurs.MethodsA prospective observational study of oral chloroquine and primaquine therapy was conducted in consecutive patients admitted to Kapit Hospital, Sarawak, Malaysian Borneo with PCR-confirmed single P. knowlesi infections. These patients were given oral chloroquine for three days, and at 24 hours oral primaquine was administered for two consecutive days, primarily as a gametocidal agent. Clinical and parasitological responses were recorded at 6-hourly intervals during the first 24 hours, daily until discharge and then weekly to day 28. Vivax malaria patients were studied as a comparator group.ResultsOf 96 knowlesi malaria patients who met the study criteria, 73 were recruited to an assessment of the acute response to treatment and 60 completed follow-up over 28 days. On admission, the mean parasite stage distributions were 49.5%, 41.5%, 4.0% and 5.6% for early trophozoites, late trophozoites, schizonts and gametocytes respectively. The median fever clearance time was 26.5 [inter-quartile range 16-34] hours. The mean times to 50% (PCT50) and 90% (PCT90) parasite clearance were 3.1 (95% confidence intervals [CI] 2.8-3.4) hours and 10.3 (9.4-11.4) hours. These were more rapid than in a group of 23 patients with vivax malaria 6.3 (5.3-7.8) hours and 20.9 (17.6-25.9) hours; P = 0.02). It was difficult to assess the effect of primaquine on P. knowlesi parasites, due to the rapid anti-malarial properties of chloroquine and since primaquine was administered 24 hours after chloroquine. No P. knowlesi recrudescences or re-infections were detected by PCR.ConclusionsChloroquine plus primaqine is an inexpensive and highly effective treatment for uncomplicated knowlesi malaria infections in humans and there is no evidence of drug resistance. Further studies using alternative anti-malarial drugs, including artemisinin derivatives, would be desirable to define optimal management strategies for P. knowlesi.

Letters to the Editor

16 June 2008 Dear Editor, TRIPLE INFECTION IN A CHILD Enteric fever, malaria and urinary tract infection are, individually, common infections in children of the tropical and the sub-tropical world. Co-infection with two disease-causing organisms may be more common than usually recognised because of the overlapping systemic manifestations. It is, however, unusual for an immunocompetent child to have three concomitant infections at a given time. The present communication is intended to report on a 4-year-old immunocompetent boy, with simultaneous enteric fever, Escherichia coli (E. coli) urinary tract infection and Plasmodium vivax (P. vivax) malaria. A 4-year-old, otherwise healthy, boy presented with high-grade intermittent fever associated with chills and rigor of 6-day duration. He also had increased frequency of micturition and pain in the abdomen for 3 days. The family and the past medical history were non-contributory. On physical examination, he was febrile (temperature: 103.5°F) and dehydrated. Intravenous fluids corrected the dehydration. He was a normally developing child with age-appropriate anthropometry. Mild pallor with cervical lymphadenopathy without evidence of malnutrition was noted. The abdomen was soft without concomitant tenderness. The spleen and the liver were palpable 2.5 cm and 2 cm below left and right costal margins, respectively. Suprapubic without renal angle tenderness was present. The other systems were normal. The laboratory tests showed: hemoglobin 8 g/dL; white blood cells: 4800/mm3 (52% neutrophils, 46% lymphocytes), platelets: 350 000/mm3. Serum urea and creatinine were normal. The urinary sediment analysis was significant for pus cells and leukocytes. The blood cultures and Widal test were positive (To 1:320) for Salmonella typhi. Ceftriaxone injection was started for enteric fever. The urine and stool cultures for the same organism were negative. The cultures of the urine, however, grew E. coli which was sensitive to ofloxacin. Thus, ofloxacin injection was added. The fever failed to subside by day 4 of therapy. Repeat urine culture at the end of 4 days was sterile. The child became increasingly anorectic and the organomegaly persisted. A Giemsa-stained peripheral blood smear showed trophozoites and schizonts of P. vivax, with parasitaemia quantitatively reported as 10–40 parasites per 100 fields. The antigen test (optiMAL) for P. vivax was positive while that for Plasmodium falciparum was negative. Chloroquine was administered using the naso-gastric tube. Oral primaquine was given as per the recommendation. There was dramatic improvement in the general condition of the child with subsidence of fever within the next 36 h. Ceftriaxone injection was given for 7 days followed by 5 days of oral cefixime. Five days of injection followed by another 5 days of oral ofloxacin was administered. The Enzyme-Linked ImmunoSorbent Assay (ELISA) for HIV-I and II and the tuberculin test were negative. He was discharged on the 10th day, having made a full clinical and microbiologic recovery. He was normal on evaluation at the end of 2 weeks. The co-occurrence of three infections in an immunocompetent child is a rare event in children belonging to the developed world. It may sometimes occur in children of the tropics and the sub-tropics because of the high prevalence of several common infections. Because constitutional symptoms like fever, anorexia and vomiting are common manifestations of most of the infections, they may not always be diagnosed individually. Furthermore, administration of broad-spectrum antimicrobial therapy may be effective for more than one organism responsible for the disease manifestations, thereby masking the presence of co-infection/s. The reported child was presumed to be immunocompetent because he had no history of life-threatening infections in the past and he was developing normally. The ELISA for HIV-I and II and the tuberculin test were non-reactive which further supports the immunocompetency of the child. The laboratory tests for the cellular and humoral immunity was not carried out. Studies from Malawi indicate that malarial parasitaemia is relatively common in children with non-typhoidal salmonella (NTS) bacteraemia.1, 2 The prevalence of any bacteraemia and of NTS bacteraemia was highest in children with severe malarial anaemia, compared with the prevalence in children with cerebral malaria associated with anaemia and in those with cerebral malaria alone.3 The authors recommended antibiotic therapy for NTS infection if bacteraemia was suspected in children with severe malarial anaemia.3 More than two-thirds of NTS episodes coincided with the peak malaria transmission season.2 The incidence of malarial parasitaemia was particularly high when the co-infecting organism was NTS than other infecting organisms. Younger age at presentation and concomitant malnutrition were two prominent risk factors predisposing to co-infection.2 A study in Kenyan children, found NTS bacteraemia to be more common in children with a recent history of malaria but not with current malarial infection.4 We reiterate the importance of ruling out mixed infections in children responding sub-optimally to therapy for a diagnosed infective condition, especially in children of the tropics and the sub-tropics.

Clindamycin/Primaquine Therapy and Secondary Prophylaxis Against Pneumocystis carinii Pneumonia in Patients With AIDS

We found a program of intravenous and subsequent oral clindamycin, combined with oral primaquine, to be effective for Pneumocystis carinii pneumonia in nine patients with AIDS. The pneumonias were either primary or recurrent and sometimes severe, with cavity formation and/or pneumothorax. Maintenance therapy at lowered dose by mouth was effective in preventing recurrence in seven patients. One patient died of other opportunistic infections on day 24, and therapy was discontinued in another on day 11 because of skin rash. We conclude that clindamycin/primaquine is effective for therapy of P carinii pneumonia in patients with AIDS, as well as for long-term secondary prophylaxis at lowered dosage.