Lawrence M. Barat

Chloroquine in Africa : critical assessment and recommendations for monitoring and evaluating chloroquine therapy efficacy in sub-Saharan Africa

Chloroquine‐resistant malaria is a major public health threat in sub‐Saharan Africa. While a few countries have already replaced chloroquine as the first‐line therapy for uncomplicated malaria or are in the process of doing so, other countries are faced with the complicated task of assessing the current status of drug resistance, making national policy‐level decisions about whether to replace chloroquine or not, and initiating a monitoring system to track changes in the efficacy of malaria therapy. There is currently no standardized approach for collecting and interpreting data on therapy efficacy. There is also no agreement as to how much chloroquine resistance or treatment failure is acceptable and how much warrants a change in treatment policy. Using data collected in 10 sites in eastern and southern Africa between 1990 and 1996, we have assessed the therapeutic response to chloroquine and investigated predictors of clinical success or failure. Based on these experiences and analyses, a standardized protocol for in vivo studies of the efficacy of malaria therapy and for approaches to designing monitoring systems are proposed. The process of making policy‐level decisions based on data collected by these systems is also discussed.

Increased Carriage of Trimethoprim/Sulfamethoxazole-Resistant Streptococcus pneumoniae in Malawian Children after Treatment for Malaria with Sulfadoxine/Pyrimethamine

Treatment of malaria with sulfadoxine/pyrimethamine and of presumed bacterial infections with trimethoprim/sulfamethoxazole (cotrimoxazole) was assessed to see if either increases the carriage of cotrimoxazole-resistant Streptococcus pneumoniae in Malawian children. Children <5 years old treated with sulfadoxine/pyrimethamine, cotrimoxazole, or no antimicrobial agent were enrolled in a prospective observational study. Nasopharyngeal swabs were taken before treatment and 1 and 4 weeks later. Pneumococci were tested for antibiotic susceptibility by broth microdilution. In sulfadoxine/pyrimethamine-treated children, the proportion colonized with cotrimoxazole-nonsusceptible pneumococci increased from 38.1% at the initial visit to 44.1% at the 4-week follow-up visit (P=.048). For cotrimoxazole-treated children, the proportion colonized with cotrimoxazole-nonsusceptible pneumococci increased from 41.5% at the initial visit to 52% at the 1-week follow-up visit (P=.0017) and returned to 41.7% at the 4-week follow-up. Expanding use of sulfadoxine/pyrimethamine to treat chloroquine-resistant malaria may have implications for national pneumonia programs in developing countries where cotrimoxazole is widely used.

A systematic approach to the development of a rational malaria treatment policy in Zambia

Despite the spread of chloroquine‐resistant Plasmodium falciparum throughout sub‐Saharan Africa, chloroquine (CQ) remains the first‐line treatment for uncomplicated infection in most countries. To assess the efficacy of CQ and sulphadoxine‐pyrimethamine (SP) in Zambia, studies using a standardized 14‐day in vivo test were conducted at 6 geographically representative sites. Febrile children ≤ 5 years of age were treated with standard doses of CQ or SP and monitored for parasitological failure (using modified WHO criteria) and clinical failure (fever with parasitaemia after completion of therapy). RII/RIII (high to moderate level) parasitological failures were identified in 34% to 70% of CQ‐treated children (total N= 300) at the 6 sites and clinical failures in 31% to 48%. SP testing at 2 sites identified RII/RIII failures in 3% and 17% of children and only 1 clinical failure at each site. Because of the high levels of CQ resistance identified in these trials, the Ministry of Health of Zambia convened a national consensus meeting which recommended that Zambias national malaria treatment policy be modified to make SP available at all health facilities for use in persons who fail initial therapy with CQ. In addition, selected sites, staff, and the methodology from these studies were used to implement a sentinel surveillance system for antimalarial drug efficacy. This systematic approach to antimalarial drug efficacy testing could be easily replicated in other countries seeking to reassess their malaria treatment policies.

DRUG RESISTANCE AMONG MALARIA AND OTHER PARASITES

Recent decades have witnessed the emergence and spread of parasites resistant to standard drug therapies, particularly malaria. Chloroquine-resistant Plasmodium falciparum has now spread to most malarial areas, and resistance to other antimalarial drugs, including mefloquine and sulfadoxine-pyrimethamine, have become significant problems in some parts of Southeast Asia and South America. Chloroquine-resistant P. vivax is well established in Papua New Guinea and Indonesia and has been reported in other areas. Trichomonas and Giardia infections resistant to metronidazole have also been documented. This article reviews the current status of drug resistance among parasites, particularly malaria, and offers strategies for managing patients with these infections.

Antibiotic resistance and serotype distribution of Streptococcus pneumoniae colonizing rural Malawian children.

Nasopharyngeal swabs were taken from 906 Malawian children <5 years old visiting rural health clinics. Pneumococcal colonization was high, 84% among all children, and occurred early, 65% of it in children <3 months old. Among pneumococcal isolates 46% were nonsusceptible to trimethoprim-sulfamethoxazole, and 21% were nonsusceptible to penicillin. Trimethoprim-sulfamethoxazole use in the previous month was a risk factor for trimethoprim-sulfamethoxazole and penicillin nonsusceptibility. Forty-three percent of isolates were serotypes included in the 7-valent pneumococcal conjugate vaccine, and 37% were vaccine-related serotypes, particularly 6A and 19A.