Please select the eligibility criteria that correspond to the clinical trial below.
Title: Interactions Between HIV and Malaria in African Children
Brief Summary: This is a prospective cohort study where HIV-infected and uninfected children will be enrolled between 6 weeks and 9 months of age and followed to the age of 21 months. All HIV-infected children will be given trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis as of 6 weeks of age. HIV-uninfected children born to HIV-infected mothers will be given TMP/SMX prophylaxis for the duration of breastfeeding and then randomized to the continuation of TMP/SMX or discontinuation of TMP/SMX prophylaxis. HIV-uninfected children born to HIV-uninfected mothers will not be given TMP/SMX prophylaxis. Study participants will be followed for all of their health care needs in a designated study clinic. All mother-child pairs will receive a basic care package including insecticide-treated bednets (ITNs) at enrollment. All HIV-infected mothers and children will receive antiretroviral therapy if eligible according to standardized World Health Organization (WHO) criteria. Study participants 4 months of age or older and at least 5 kg will be randomized to treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) at the time of their first diagnosis of uncomplicated malaria. Study participants will receive the same antimalarial treatment regimen for all future episodes of uncomplicated malaria. Study participants less than 4 months of age or less than 5 kg diagnosed with malaria and all episodes of complicated malaria will be treated with quinine in accordance with local guidelines.

The investigators will test the hypotheses that:

1. TMP/SMX prophylaxis is highly effective in preventing malaria in both HIV-infected and HIV-uninfected children
2. The use of TMP/SMX prophylaxis is associated with an increased risk of infection with malaria parasites containing antifolate resistance-conferring mutations.
3. The use of antiretroviral (ARV) drugs is associated with a decreased incidence of malaria.
4. The efficacy, safety, and tolerability of AL and DP for the treatment of uncomplicated malaria differ.

   In 2008, we received approval and funding to extend the trial until 2012. We are now following all children through 5 years of age. First randomization to continue or discontinue TMP/SMX prophylaxis in our HIV-exposed population occurs 6-8 weeks after cessation of breastfeeding when HIV status can be confirmed as negative by DNA PCR. A second randomization occurs at 2 years of age in our HIV-exposed participants. At that point all HIV-exposed children who were originally randomized to continue TMP/SMX prophylaxis are again randomized to either immediately discontinue TMP/SMX prophylaxis or continue prophylaxis until age 4 years. All children will be off TMP/SMX between 4 and 5 years of age.

   We have also added an additional hypothesis to test during the study extension:
5. Prolonged TMP/SMX prophylaxis will result in an increased incidence of malaria in children in the year immediately following cessation of prophylaxis compared to children who have not used prophylaxis for over a year and those who have never been on prophylaxis.


Options:
A: Inclusion Criteria:

* Age 6 months - 10 years
* Residents of research area (5 km around the clinic)
* Willingness to come for complete scheduled follow-up.
* Uncomplicated malaria with P. falciparum mono-infection
* Parasitaemia of 1000-200,000 parasites/ul
* Temperature \> 37.5°C and \< 39.5°C, or history of fever in previous 24 hours.
* No history of adverse reactions to AL
* Understanding of the procedures of the study by parent or guardian and willing to participate by signing informed consent forms.

Exclusion Criteria:

* General signs of severe malaria
* Haemoglobin concentration \< 5g/dl
* Presence of disease other than malaria causing febrile conditions
* Mixed infection with P. malariae or other non-falciparum malaria species
* Unwilling to participate and sign informed consent forms.
B: Inclusion Criteria:

* Age: 5 - 60 years old
* Fever (axillary temperature equal or higher than 37,5 °C) or history of fever in the previous 24 hours
* Monoinfection with P. falciparum, with parasitic density between 1,000 and 200,000 par/µl
* Informed consent provided by patient or parent or legal tutor

  • Exclusion criteria:
* Mixed malaria infection
* Pregnancy or breastfeeding to child ≤ 6 months of age
* One or more danger signs or any sign of severe or complicated malaria
* A concomitant severe disease
* History of treatment with mefloquine in the last 60 days or chloroquine, primaquine or quinine within the 14 days before the present episode
* History of neuropsychiatric disease
* History of hypersensitivity reactions to artemisinins or mefloquine
* History of splenectomy
C: Inclusion Criteria:

* Male and female patients at least one 1year of age and weighing more than 10kg.
* Microscopic confirmation of P. falciparum and /or P.vivax infection (any parasitaemia).
* Fever (axillary temperature \>37.5C) or history of fever in the last 48 hours.
* Able to participate in the trial and comply with the clinical trial protocol
* Written informed consent to participate in trial; verbal consent in presence of literate witness is required for illiterate patients, and written consent from parents/guardian for children below age of consent

Exclusion Criteria:

* Pregnancy or lactation
* Inability to tolerate oral treatment
* Signs/symptoms indicative of severe/complicated malaria or warning signs requiring parenteral treatment (See Appendix II)
* Known hypersensitivity or allergy to artemisinin derivatives
* Serious underlying disease (cardiac, renal or hepatic)
* Parasitaemia \>4%
D: Inclusion Criteria:

1. Age 6 weeks to 9 months
2. Documented HIV-1 status of mother and child
3. Agreement to come to the study clinic for any febrile episode or other illness
4. Agreement to avoid medications administered outside the study protocol
5. Guardian age 18 years or older (no age limit for parents)
6. Parent or guardian willing to provide informed consent
7. Residence within a 30 km radius of the study clinic

Exclusion Criteria:

1. HIV-exposed infants who have already stopped receiving TMP/SMX as a result of having stopped breastfeeding and having been tested HIV-negative before screening
2. Intention to move more than 30 km from the study clinic during the follow-up period
3. History of allergy or sensitivity to AL or DP or TMP/SMX
4. Active medical problem requiring in-patient evaluation at the time of screening

Answer: D